内皮素-1对鸡血流动力学的影响及其在肉鸡肺动脉高压综合征发病机制中的作用
|
摘要
尽管对于哺乳动物已经确切证明内皮素是以自分泌和旁分泌的方式作用于靶细胞膜上的受体，对动物基础血压和一些疾病的发病过程有重要病理生理意义，但对于禽类，无论是内皮素的生理还是病理作用，都研究甚少。通过这个研究，首次证明内皮素-1有维持鸡体循环和肺循环基本血压的作用，并参与了低温诱发肉鸡腹水肺动脉高压综合征的发病过程。
第一部分 内皮素-1对鸡血流动力学的影响
1．用外源性ET-1注射于正常蛋鸡和肉鸡翼静脉，观察到PACP、PASP、FACP、FASP、RVSP、RVDP升高并随时间变化的曲线具有双相性和双向性，呈先降后升的趋势，也观察到RV+dp/dt和HR下降，而且ET-1对这些检测指标的影响都呈剂量依赖性，即ET-1浓度越高，指标的变化越大；对于本试验选取的蛋鸡和肉鸡，ET-1对股动脉压的影响比肺动脉压大，ET-1对蛋鸡和肉鸡同一指标的作用没有明显差异。通过这个试验证明了外源性ET-1能够改变家禽体循环和肺循环的生理平衡，主要表现为升高血压。
2．本研究证明翼静脉注射ET-1 Ab可以降低肺动脉压、股动脉压、右心室内压和心率，提示ET-1有维持家禽基本血压的作用，因ET-1 Ab与体内ET-1结合，使ET-1不能到达受体，从而降低ET-1的血管收缩作用。试验中发现抗体对于不同系统的血压作用不同，对体循环的影响比肺循环大；对肉鸡血流动力学的影响比对蛋鸡大，提示蛋鸡和肉鸡血液中ET-1的游离与结合状态比值不同。本试验结果说明，在维持家禽正常肺动脉血压的过程中，ET-1是保证肺血管张力的基本条件之一，所以，若改变和/或阻断ET-1生物学作用，就能改变家禽血流动力学。
3．用ET_AR特异性受体拮抗剂BQ123注射于正常蛋鸡和肉鸡翼静脉，也观察到可以降低肺动脉压、股动脉压、右心室内压和心率，使心肌收缩速率变大，而且BQ123对这些检测指标的影响均呈剂量依赖性，即BQ123浓度越高，指标变化越大。BQ123与ET_AR特异性结合，竞争性的阻断ET-1与ET_AR结合，使受体后信息通路不能被启动，因而使血管平滑肌和心肌紧张度下降，结果血压和心室内压下降。通过这个试验可以反证ET-1参与了家禽基本血压的生理调节。
第二部分 内皮素-1在肉鸡肺动脉高压综合征发病机制中的作用
4．常温肉鸡和低温诱发的肺动脉高压肉鸡翼静脉注射相同浓度的ET-1，发现低温肉鸡在出现PH后，ET-1仍然可以引起肺循环和体循环的血流动力学发生改变，即使肺动脉压和股动脉压都升高，但升高的幅度比常温肉鸡低，说明肺血管和心脏闲置的ET_AR发生改变(减少)，外源性ET-1与减少了的ET_AR结合，对肺动脉和股动脉的升压作用就会明显低于正常肉鸡，即PH肉鸡循环对ET-1的反应性下降。这个试验初步说明肉鸡发生肺动脉高压时，有ET-1的参与。
5．通过注射ET-1 Ab观察到肺动脉高压肉鸡肺动脉压变化比常温肉鸡大，而股动脉压没有明显变化，说明PH时，肺循环ET-1含量增加，体循环没有明显改变，提示低温诱发肉鸡PH时，
中国农业大学博士学位论文
一
ET－且的增加只在部分器官，血浆中ETI的浓度不能完全代表血管内 ETI的变化，而通过ETI Ah
与ET中和，可以间接反映PH时机体ET－l变化的特点。这个试验也证明ET－1参与了肉鸡肺
动脉高压综合征的发病过程。
6．用BQ123观察到低温诱发的肺动脉高压肉鸡股动脉压和肺动脉压都比正常肉鸡下降显著，
提示肺动脉高压肉鸡心脏和肺血管等某些器官组织发生 ETAR数量和密度的改变，而当 BQ123
与ETI竞争性的和ETAR结合后，逆转了ET－l的血管和心脏收缩作用，用受体抑制方法间接证
明了肺动脉高压时ET－l在肉鸡肺动脉高压发病机制中占有重要地位。
7．通过定时定量于低温肉鸡腹腔内注射BQ123，检测PACP、PASP、FACP、FASP、RVSP、
RVDP、RVtdpldt、HR、PCV和AHI这些指标，结果表明ETAR特异性受体桔抗剂BQ123能够
预防低温诱发肉鸡肺动脉高压，保护肺动脉和右心正常的生理功能。因为BQ123是通过桔抗ET－1
的作用起到预防和保护作用的，所以本试验结果又一次用反证法，验证了ET－l参与了肉鸡腹水
肺动脉高压的发病过程，而且为肉鸡肺动脉高压综合征提供了新的治疗途径。
本试验从宏观角度，用外源性注射ETI、受体抑制和受体前抑制三种方式直接证明正常生理
条件下，ET－l—ETAR有维持家禽基本血压的作用，还发现ETN受体桔抗剂BQ123可以预防低
温诱发的肉鸡肺动脉高压，为进一步研究ET－ETR系统在家禽某些病理生理机制中的作用提供理
论依据。
There is not much information about the effects of endothelin-1 (ET-1), a potent endogenous constrictor of vascular, on haemodynamics or which ET receptor subtypes mediate ET-1-induced vasoconstrictive action in the poultry. ET-1 not only causes a potent and prolonged vasoconstriction but also are known to enhance cell proliferation and to stimulate extracellular matrix accumulation in vivo and in vitro. To clarify the actions of ET-1 underlying pulmonary circulation and systemic circulation in poultry, we investigated the effect of ET-1, BQ123 (a selective ETA receptor antagonist) and ET-1 antibody (ET-1 Ab) on the pulmonary arterial contract pressure (PACP), pulmonary arterial stretch pressure (PASP), femoral arterial contract pressure (FACP), femoral arterial stretch pressure (FASP), right ventricular systolic pressure (RVSP), the maximum increasing rate of right ventricular (RV+dp/dt), heart rate (HR) in normal laying-egg chickens, broilers with and without pulmonary hypertension (PH). We also studied th
e effects of long-term BQ-123 treatment on the broilers exposed to low ambient temperatures.
1. ET-1 produced dose-dependent increases in PACP, PASP, FACP, FASP, RVSP, RVDP, which were rapidly decreases in onset preceded sustained biphasic ascending (first phase peaking at 1-2 minutes; second phase peaking at 10-15 minutes) after injecting 1.0 and 2.0 ug/kg ET-1 through wing veins, whereas, decreases of RV+dp/dt and HR were observed. No distinctness was found between the laying-egg chickens and broilers and there are more change in pulmonary than systemic circulation in either bird.
2. ET-1 Ab (1:2500) (i.v) caused descending in PACP, PASP, FACP, FASP, RVSP, and a little ascending in RV+dp/dt and HR. The results revealed that pulmonary vessels are more sensitive to ET-1-induced vasoconstriction than systemic vessels and showed endogenous ET-1 is responsible for the basic balance of blood pressure in chicks.
3. 2.0 ug/kg BQ123 (i.v.) induced PACP, PASP, FACP, FASP, RVSP increase and RV+dp/dt, HR decrease more significantly than 0.4 ug/kg BQ123, whereas, there was no evident change in saline control. These results suggest that ET-1 ?ETAR play an important role in the regulation of in systemic and pulmonary circulations.
4. That much fewer increases in PACP, PASP, FACP, FASP were caused by 2.0 ug/kg ET-1 (i.v.) in broilers with PH induced by low ambient temperatures than normal broilers indicates there is some change of ET-1 in the development of PH in broilers.
5. That ET-1 Ab (1:2500) induced more decreases of PACP, PASP in broiler with pulmonary hypertension induced by low ambient temperatures than the normal ones but not FACP, FASP suggests
ET-1 take part in the development of PH in broilers.
6. The much more decreases of PACP, PASP, FACP, FASP induced by BQ123 (2.0 ng/kg, i.v;) in PH broilers than normal broilers also demonstrates the impdrtance of ET-l in the development of PH in broilers.
7. Long-term (14 days) BQ-123 pretreatment greatly prevented pulmonary hypertension in the broilers exposed in low ambient temperatures (LAT), while LAT led to severe PH in saline and blank groups accompanied by increases in RVSP, PCV, AHI, HR and a decrease in RV |dp/dt|. All these suggest that endothelin-1 play an important role in the development of pulmonary hypertension caused by LAT and that BQ123 ( an ETAR antagonist) may be a new therapeutic agent for LAT-induced pulmonary hypertension in broilers.
The study demonstrates considerable similarities in the complex haemodynamic effects of ET-l in chicks. ET-l is one of the factors that regulate the blood vessels rhythm of normal chicks., The study Also indicates ET-l play an important role in development of PH in broilers and BQ123 can prevent PH. Accordingly Future studies are needed to show whether desensitization or upregulation/downregulation of the ETAR may contribute to the increase in circulating ET-l levels in pulmonary hypertension in broilers. The blockage of the ETAR pathway by BQ123 is,a new way to reduce
第一部分 内皮素-1对鸡血流动力学的影响
1．用外源性ET-1注射于正常蛋鸡和肉鸡翼静脉，观察到PACP、PASP、FACP、FASP、RVSP、RVDP升高并随时间变化的曲线具有双相性和双向性，呈先降后升的趋势，也观察到RV+dp/dt和HR下降，而且ET-1对这些检测指标的影响都呈剂量依赖性，即ET-1浓度越高，指标的变化越大；对于本试验选取的蛋鸡和肉鸡，ET-1对股动脉压的影响比肺动脉压大，ET-1对蛋鸡和肉鸡同一指标的作用没有明显差异。通过这个试验证明了外源性ET-1能够改变家禽体循环和肺循环的生理平衡，主要表现为升高血压。
2．本研究证明翼静脉注射ET-1 Ab可以降低肺动脉压、股动脉压、右心室内压和心率，提示ET-1有维持家禽基本血压的作用，因ET-1 Ab与体内ET-1结合，使ET-1不能到达受体，从而降低ET-1的血管收缩作用。试验中发现抗体对于不同系统的血压作用不同，对体循环的影响比肺循环大；对肉鸡血流动力学的影响比对蛋鸡大，提示蛋鸡和肉鸡血液中ET-1的游离与结合状态比值不同。本试验结果说明，在维持家禽正常肺动脉血压的过程中，ET-1是保证肺血管张力的基本条件之一，所以，若改变和/或阻断ET-1生物学作用，就能改变家禽血流动力学。
3．用ET_AR特异性受体拮抗剂BQ123注射于正常蛋鸡和肉鸡翼静脉，也观察到可以降低肺动脉压、股动脉压、右心室内压和心率，使心肌收缩速率变大，而且BQ123对这些检测指标的影响均呈剂量依赖性，即BQ123浓度越高，指标变化越大。BQ123与ET_AR特异性结合，竞争性的阻断ET-1与ET_AR结合，使受体后信息通路不能被启动，因而使血管平滑肌和心肌紧张度下降，结果血压和心室内压下降。通过这个试验可以反证ET-1参与了家禽基本血压的生理调节。
第二部分 内皮素-1在肉鸡肺动脉高压综合征发病机制中的作用
4．常温肉鸡和低温诱发的肺动脉高压肉鸡翼静脉注射相同浓度的ET-1，发现低温肉鸡在出现PH后，ET-1仍然可以引起肺循环和体循环的血流动力学发生改变，即使肺动脉压和股动脉压都升高，但升高的幅度比常温肉鸡低，说明肺血管和心脏闲置的ET_AR发生改变(减少)，外源性ET-1与减少了的ET_AR结合，对肺动脉和股动脉的升压作用就会明显低于正常肉鸡，即PH肉鸡循环对ET-1的反应性下降。这个试验初步说明肉鸡发生肺动脉高压时，有ET-1的参与。
5．通过注射ET-1 Ab观察到肺动脉高压肉鸡肺动脉压变化比常温肉鸡大，而股动脉压没有明显变化，说明PH时，肺循环ET-1含量增加，体循环没有明显改变，提示低温诱发肉鸡PH时，
中国农业大学博士学位论文
一
ET－且的增加只在部分器官，血浆中ETI的浓度不能完全代表血管内 ETI的变化，而通过ETI Ah
与ET中和，可以间接反映PH时机体ET－l变化的特点。这个试验也证明ET－1参与了肉鸡肺
动脉高压综合征的发病过程。
6．用BQ123观察到低温诱发的肺动脉高压肉鸡股动脉压和肺动脉压都比正常肉鸡下降显著，
提示肺动脉高压肉鸡心脏和肺血管等某些器官组织发生 ETAR数量和密度的改变，而当 BQ123
与ETI竞争性的和ETAR结合后，逆转了ET－l的血管和心脏收缩作用，用受体抑制方法间接证
明了肺动脉高压时ET－l在肉鸡肺动脉高压发病机制中占有重要地位。
7．通过定时定量于低温肉鸡腹腔内注射BQ123，检测PACP、PASP、FACP、FASP、RVSP、
RVDP、RVtdpldt、HR、PCV和AHI这些指标，结果表明ETAR特异性受体桔抗剂BQ123能够
预防低温诱发肉鸡肺动脉高压，保护肺动脉和右心正常的生理功能。因为BQ123是通过桔抗ET－1
的作用起到预防和保护作用的，所以本试验结果又一次用反证法，验证了ET－l参与了肉鸡腹水
肺动脉高压的发病过程，而且为肉鸡肺动脉高压综合征提供了新的治疗途径。
本试验从宏观角度，用外源性注射ETI、受体抑制和受体前抑制三种方式直接证明正常生理
条件下，ET－l—ETAR有维持家禽基本血压的作用，还发现ETN受体桔抗剂BQ123可以预防低
温诱发的肉鸡肺动脉高压，为进一步研究ET－ETR系统在家禽某些病理生理机制中的作用提供理
论依据。
There is not much information about the effects of endothelin-1 (ET-1), a potent endogenous constrictor of vascular, on haemodynamics or which ET receptor subtypes mediate ET-1-induced vasoconstrictive action in the poultry. ET-1 not only causes a potent and prolonged vasoconstriction but also are known to enhance cell proliferation and to stimulate extracellular matrix accumulation in vivo and in vitro. To clarify the actions of ET-1 underlying pulmonary circulation and systemic circulation in poultry, we investigated the effect of ET-1, BQ123 (a selective ETA receptor antagonist) and ET-1 antibody (ET-1 Ab) on the pulmonary arterial contract pressure (PACP), pulmonary arterial stretch pressure (PASP), femoral arterial contract pressure (FACP), femoral arterial stretch pressure (FASP), right ventricular systolic pressure (RVSP), the maximum increasing rate of right ventricular (RV+dp/dt), heart rate (HR) in normal laying-egg chickens, broilers with and without pulmonary hypertension (PH). We also studied th
e effects of long-term BQ-123 treatment on the broilers exposed to low ambient temperatures.
1. ET-1 produced dose-dependent increases in PACP, PASP, FACP, FASP, RVSP, RVDP, which were rapidly decreases in onset preceded sustained biphasic ascending (first phase peaking at 1-2 minutes; second phase peaking at 10-15 minutes) after injecting 1.0 and 2.0 ug/kg ET-1 through wing veins, whereas, decreases of RV+dp/dt and HR were observed. No distinctness was found between the laying-egg chickens and broilers and there are more change in pulmonary than systemic circulation in either bird.
2. ET-1 Ab (1:2500) (i.v) caused descending in PACP, PASP, FACP, FASP, RVSP, and a little ascending in RV+dp/dt and HR. The results revealed that pulmonary vessels are more sensitive to ET-1-induced vasoconstriction than systemic vessels and showed endogenous ET-1 is responsible for the basic balance of blood pressure in chicks.
3. 2.0 ug/kg BQ123 (i.v.) induced PACP, PASP, FACP, FASP, RVSP increase and RV+dp/dt, HR decrease more significantly than 0.4 ug/kg BQ123, whereas, there was no evident change in saline control. These results suggest that ET-1 ?ETAR play an important role in the regulation of in systemic and pulmonary circulations.
4. That much fewer increases in PACP, PASP, FACP, FASP were caused by 2.0 ug/kg ET-1 (i.v.) in broilers with PH induced by low ambient temperatures than normal broilers indicates there is some change of ET-1 in the development of PH in broilers.
5. That ET-1 Ab (1:2500) induced more decreases of PACP, PASP in broiler with pulmonary hypertension induced by low ambient temperatures than the normal ones but not FACP, FASP suggests
ET-1 take part in the development of PH in broilers.
6. The much more decreases of PACP, PASP, FACP, FASP induced by BQ123 (2.0 ng/kg, i.v;) in PH broilers than normal broilers also demonstrates the impdrtance of ET-l in the development of PH in broilers.
7. Long-term (14 days) BQ-123 pretreatment greatly prevented pulmonary hypertension in the broilers exposed in low ambient temperatures (LAT), while LAT led to severe PH in saline and blank groups accompanied by increases in RVSP, PCV, AHI, HR and a decrease in RV |dp/dt|. All these suggest that endothelin-1 play an important role in the development of pulmonary hypertension caused by LAT and that BQ123 ( an ETAR antagonist) may be a new therapeutic agent for LAT-induced pulmonary hypertension in broilers.
The study demonstrates considerable similarities in the complex haemodynamic effects of ET-l in chicks. ET-l is one of the factors that regulate the blood vessels rhythm of normal chicks., The study Also indicates ET-l play an important role in development of PH in broilers and BQ123 can prevent PH. Accordingly Future studies are needed to show whether desensitization or upregulation/downregulation of the ETAR may contribute to the increase in circulating ET-l levels in pulmonary hypertension in broilers. The blockage of the ETAR pathway by BQ123 is,a new way to reduce
引文
[1] Hickey KA, Rubanyi G, Paul RJ, et al. Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am J Physiol, 1985, 248(5 Pt 1): C550-6
[2] Gillespie MN, Owasoyo JO, McMurtry IF, et al. Sustained coronary vasoconstriction provoked by a peptidergic substance released from endothelial cells in culture. J Pharmacol Exp Ther, 1986, 236(2): 339-43
[3] O'Brien RF, Robbins RJ, McMurtry IF. Endothelial cells in culture produce a vasoconstrictor substance. J Cell Physiol, 1987, 132(2): 263-70
[4] Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988,332(6163):411-5
[5] Yanagisawa M, Inoue A, Ishikawa T, et al. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc.Natl Acad Sci, U S A 1988, 85(18): 6964-7
[6] Itoh Y, Yanagisawa M, Ohkubo S, et al. Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: identity of human and porcine endothelin. FEBS Lett, 1988, 231(2): 440-4
[7] Tomobe Y, Miyauchi T, Saito A, Yanagisawa M, Kimura S, Goto K, Masaki T. Effects of endothelin on the renal artery from spontaneously hypertensive and Wistar Kyoto rats. Eur J Pharmacol. 1988, 152(3): 373-4
[8] Hirata Y, Yoshimi H, Takata S, et al. Cellular mechanism of action by a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells. Biochem Biophys Res Commun, 1988, 154(3): 868-75
[9] Fukuda Y, Hirata Y, Yoshimi H, et al. Endothelin is a potent secretagogue for atrial natriuretic peptide in cultured rat atrial myocytes. Biochem Biophys Res Commun, 1988,155(1): 167-72
[10] Yanagisawa M, Inoue A, Ishikawa T, et al. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc Natl Acad Sci, U S A 1988, 85(18): 6964-7
[11] Uchida Y, Ninomiya H, Saotome M, et al. Endothelin, a novel vasoconstrictor peptide, as potentbronchoconstrictor. Eur J Pharmacol, 1988,154(2):227-8
[12] Chander CL, Moore AR, Desa FM, et al. The local modulation of vascular permeability by endothelial cell derived products. J Pharm Pharmacol, 1988, 40(10): 745-6
[13] Wiklund NP, Ohlen A, Cederqvist B. Inhibition of adrenergic neuroeffector transmission by endothelin in the guinea-pig femoral artery. Acta Physiol Scand, 1988, 134(2): 311-2
[14] Auguet M, Delaflotte S, Chabrier PE, et al. Endothelin and Ca~(++) agonist Bay K 8644: different vasoconstrictive properties. Biochem Biophys Res Commun, 1988, 156(1): 186-92
[15] Kloog Y, Ambar I, Sokolovsky M, et al. Sarafotoxin, a novel vasoconstrictor peptide:
phosphoinositide hydrolysis in rat heart and brain. Science, 1988, 242(4876): 268-70
[16] Firth JD, Ratcliffe PJ, Raine AE, et al, Endothelin: an important factor in acute renal failure? Lancet, 1988, 2(8621): 1179-82
[17] Goetz KL, Wang BC, Madwed JB, et al. Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs. Am J Physiol, 1988, 255(6 Pt 2): R1064-8
[18] Van Renterghem C, Vigne P, Barhanin J, et al. Molecular mechanism of action of the vasoconstrictor peptide endothelin. Biochem Biophys Res Commun, 1988, 157(3): 977-85
[19] Resink TJ, Scott-Burden T, Buhler FR. Endothelin stimulates phospholipase C in cultured vascular smooth muscle cells. Biochem Biophys Res Commun, 1988, 157(3): 1360-8
[20] Brain SD, Tippins JR, Williams TJ. Endothelin induces potent microvascular constriction. Br J Pharmacol, 1988, 95(4): 1005-7
[21] Kimura S, Kasuya Y, Sawamura T, Shinmi O, et al. Structure-activity relationships of endothelin: importance of the C-terminal moiety. Biochem Biophys Res Commun. 1988, 156(3): 1182-6
[22] Kumagaye S, Kuroda H, Nakajima K, et al. Synthesis and disulfide structure determination of porcine endothelin: an endothelium-derived vasoconstricting peptide. Int J Pept Protein Res, 1988, 32(6): 519-26
[23] Nakajima K, Kumagaye S, Nishio H, et al. Synthesis of endothelin-1 analogues, endothelin-3, and sarafotoxin S6b: structure-activity relationships. J Cardiovasc Pharmacol, 1989,13 (Suppl 5):S8-12
[24] Nayler WG, Gu XH, Casley DJ. Sarafotoxin S6c is a relatively weak displacer of specifically bound 125I-endothelin. Biochem Biophys Res Commun, 1989, 161(1): 89-94
[25] Bdolah A, Wollberg Z, Fleminger G, et al. SRTX-d, a new native peptide of the endothelin/sarafotoxin family. FEBS Lett, 1989, 256(1-2): 1-3
[26] Inoue A, Yanagisawa M, Kimura S, et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci, U S A 1989,86(8):2863-7
[27] Saida K, Mitsui Y, Ishida N. A novel peptide, vasoactive intestinal contractor, of a new (endothelin) peptide family. Molecular cloning, expression, and biological activity. J Biol Chem, 1989, 264(25): 14613-6
[28] Kishi F, Minami K, Okishima N, Novel 31-amino-acid-length endothelins cause constriction of vascular smooth muscle. Biochem Biophys Res Commun, 1998, 248(2): 387-90
[29] Kido T, Sawamura T, Masaki T. The processingpathway of endothelin-1 production. J Cardiovasc Pharmacol, 1998, 31(Suppl 1): S13-5
[30] Kido T, Sawamura T, Hoshikawa H, et al. Processing of proendothelin-1 at the C-terminus of big endothelin-1 is essential for proteolysis by endothelin-converting enzyme-1 in vivo. Eur J Biochem, 1997, 244(2): 520-6
[31] Bloch KD, Eddy RL, Shows TB, et al. cDNA cloning and chromosomal assignment of the gene encoding endothelin 3. J Bioi Chem, 1989, 264(30): 18156-61
[32] Inoue A, Yanagisawa M, Takuwa Y, et al. The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression. J Biol Chem, 1989, 264(25): 14954-9
[33] Yanagisawa M, Inoue A, Takuwa Y, et al. The human preproendothelin-1 gene: possible regulation by endothelial phosphoinositide turnover signaling. J Cardiovasc Pharmacol, 1989, 13 (Suppl 5): S13-7
[34] Chart TS, Lin CX, Chan WY, et al. Mouse preproendothelin-1 gene. cDNA cloning, sequence analysis and determination of sites of expression during embryonic development. Eur J Biochem, 1995, 234(3): 819-26
[35] Denault JB, Claing A, D'Orleans-Juste P, et al. Processing of proendothelin-1 by human furin convertase. FEBS Lett, 1995, 362(3): 276-80
[36] Blals V, Fugere M, Denault JB, Processing of proendothelin-1 by members of the subtilisin-like pro-protein convertase family. FEBS Lett, 2002, 524(1-3): 43-8
[37] Hirata Y, Matsunaga T, Ando K, et al. Presence of endothelin-1-like immunoreactivity in human cerebrospinal fluid. Biochem Biophys Res Commun, 1990, 166(3): 1274-8
[38] Kimura S, Kasuya Y, Sawamura T, et al. Conversion of big endothelin-1 to 21-residue endothelin-1 is essential for expression of full vasoconstrictor activity: structure-activity relationships of big endothelin-1. J Cardiovasc Pharmacol, 1989, 13(Suppl 5): S5-7
[39] Sawamura T, Kimura S, Shinmi O, Characterization of endothelin converting enzyme activities in soluble fraction of bovine cultured endothelial cells. Biochem Biophys Res Commun, 1990, 169(3): 1138-44
[40] Wu-Wong JR, Budzik GP, Devine EM, et al. Characterization of endothelin converting enzyme in rat lung. Biochem Biophys Res Commun, 1990, 171(3): 1291-6
[41] Schweizer A, Valdenaire O, Nelbock P, et al. Human endothelin-converting enzyme (ECE-1): three isoforms with distinct subcellular localizations. Biochem J, 1997, 328 (Pt 3): 871-7
[42] Valdenaire O, Lepailleur-Enouf D. A fourth isoform of endothelin-converting enzyme (ECE-1) is generated from an additional promoter molecular cloning and characterization. Eur J Biochem, 1999, 264(2): 341-9
[43] Muller L, Barret A, Etienne E, et al. Heterodimerization of Endothelin-converting Enzyme-1 Isoforms Regulates the Subcellular Distribution of This Metalloprotease. J Biol Chem, 2003, 278(1): 545-55
[44] Lüscher TF, Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation, 2000, 102(19): 2434-40.
[45] Ehrenreich H, Anderson RW, Fox CH, et al. Endothelins, peptides with potent vasoactive properties, are produced by human macrophages. J Exp Med, 1990, 172(6): 1741-8
[46] Kobayashi Y, Sakamoto Y, Shibasaki M,Human alveolar macrophages synthesize endothelins by thrombin. J Immunol, 1997, 158(11): 5442-7
[47] Nishida M, Springhom JP, Kelly RA, et al. Cell-cell signaling between adult rat ventricular myocytes and cardiac microvascular endothelial cells in heterotypic primary culture. J Clin Invest,
1993, 91(5): 1934-41
[48] De Keulenaer GW, Andries LJ, Sys SU. Endothelin-mediated positive inotropic effect induced by reactive oxygen species in isolated cardiac muscle. Circ Res, 1995, 76(5): 878-84
[49] Hemsen A, Lundberg JM. Presence of endothelin-1 and endothelin-3 in peripheral tissues and central nervous system of the pig. Regul Pept, 1991, 36(1): 71-83
[50] Dean R, Zhuo J, Alcorn D, et al. Cellular distribution of 125I-endothelin-1 binding in rat kidney following in vivo labeling. Am J Physiol, 1994, 267(5 Pt 2): F845-52
[51] Masaki T. Possible role of endothelin in endothelial regulation of vascular tone. Annu Rev Pharmacol Toxicol, 1995, 35:235-55
[52] Hislop AA, Zhao YD, Springall DR, et al. Postnatal changes in endothelin-1 binding in porcine pulmonary vessels and airways. Am J Respir Cell Mol Biol, 1995, 12(5): 557-66
[53] Chakravarthy U, Douglas AJ, Bailie JR, et al. Immunoreactive endothelin distribution in ocular tissues. Invest Ophthalmol Vis Sci, 1994, 35(5): 2448-5
[54] Casasco A, Benazzo M, Casasco M, et al. Occurrence, distribution and possible role of the regulatory peptide endothelin in the nasal mucosa. Cell Tissue Res, 1993, 274(2): 24l-7
[55] Svane D, Larsson B, Alm P, et al. Endothelin-1: immunocytochemistry, localization of binding sites, and contractile effects in human uteroplacental smooth muscle. Am J Obstet Gynecol, 1993, 168(1 Pt l): 233-41
[56] Davenport AP, Nunez DJ, Brown MJ. Binding sites for 125I-labelled endothelin-1 in the kidneys: differential distribution in rat, pig and man demonstrated by using quantitative autoradiography. Clin Sci (Lond), 1989, 77(2): 129-31
[57] Yoshimi H, Hirata Y, Fukuda Y, Regional distribution of immunoreactive endothelin in rats. Peptides, 1989, 10(4): 805-8
[58] Kloog Y, Ambar I, Sokolovsky M, et al. Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain. Science, 1988, 242(4876): 268-70
[59] Pemow J, Hemsen A, Lundberg JM. Tissue specific distribution, clearance and vascular effects of endothelin in the pig. Biochem Biophys Res Commun, 1989, 161 (2): 647-53
[60] Sirvio ML, Metsarinne K, Saijonmaa O, et al. Tissue distribution and half-life of 125I-endothelin in the rat: importance of pulmonary clearance. Biochem Biophys Res Commun, 1990, 167(3): 1191-5
[61] Shiba R, Yanagisawa M, Miyauchi T, et al. Elimination of intravenously injected endothelin-1 from the circulation of the rat. J Cardiovasc Pharmacol, 1989, 13(Suppl 5): S98-101
[62] Anggard E, Galton S, Rae G, et al. The fate of radioiodinated endothelin-1 and endothelin-3 in the rat. J Cardiovasc Pharmacoi, 1989, 13 (Suppl 5): S46-9
[63] Fukuroda T, Fujikawa T, Ozaki S, et al. Clearance of circulating endothelin-1 by ETB receptors in rats. Biochem Biophys Res Commun, 1994, 199(3): 1461-5
[64] Burkhardt M, Barton M, Shaw SG. Receptor- and non-receptor-mediated clearance of big-endothelin and endothelin-1: differential effects of acute and chronic ETA receptor blockade.
J Hypertens, 2000, 18(3): 273-9
[65] Bolger GT, Liard F, Krogsrud R, et al. Tissue specificity of endothelin binding sites. J Cardiovasc Pharmacol, 1990, 16(3): 367-75
[66] Sirvio ML, Saijonmaa O, Metsarinne K, et al. Degradation of endothelin-1 by extracts of rat lung, kidney, and liven Regul Pept, 1995, 55(3): 219-25
[67] Dupuis J, Goresky CA, Foumier A.Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors. J Appl Physiol, 1996, 81 (4): 1510-5
[68] Reinhart GA, Preusser LC, Burke SE, et al. Hypertension induced by blockade of ET_B receptors in conscious nonhuman primates: role of ETA receptors. Am J Physiol Heart Circ Physiol, 2002, 283(4): H1555-H1561.
[69] Koseki C, Imai M, Hiram Y, et al. Autoradiographic distribution in rat tissues of binding sites for endothelin: a neuropeptide? Am J Physiol, 1989, 256(4 Pt 2): R858-66
[70] Power RF, Wharton J, Zhao Y, et al. Autoradiographic localization ofendothelin-1 binding sites in the cardiovascular and respiratory systems.J Cardiovasc Pharmacol, 1989, 13(Suppl 5): S50-6
[71] Arai H, Hod S, Aramori I, et al. Cloning and expression of a cDNA encoding an endothelin receptor. Nature, 1990, 348(6303): 730-2
[72] Ferro CJ, Webb DJ. The clinical potential of endothelin receptor antagonists in cardiovascular medicine. Drugs, 1996,51(1):12-27
[73] Douglas SA, Meek TD, Ohlstein EH. Novel receptor antagonists welcome a new era in endothelin biology. Trends Pharmacol Sci, 1994, 15(9): 313-6
[74] Kame S, Jayawickreme CK, Lerner MR. Cloning and characterization of an endothelin-3 specific receptor (ETC receptor) from Xenopus laevis dermal melanophores. J Biol Chem, 1993, 268(25): 19126-33
[75] Karet FE, Kuc RE, Davenport AP. Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney. Kidney Int, 1993, 44(1): 3642
[76] Molenaar P, O'Reilly G, Sharkey A, et al. Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium. Circ Res, 1993, 72(3): 526-38
[77] Warner TD, Mitchell JA, de Nucci G, et al. Endothelin-1 and endothelin-3 release EDRF from isolated perfused arterial vessels of the rat and rabbit. J Cardiovasc Pharmacol, 1989, 13 (Suppl 5): S85-8
[78] Hirata Y, Emori T, Eguchi S, et al. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest, 1993,91(4): 1367-73
[79] Davenport AP, O'Reilly G, Kuc RE. Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA sub-type. Br J Pharmacol, 1995, 114(6): 1110-6
[80] Clozel M, Gray GA, Breu V, et al. The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Commun, 1992, 186(2): 867-73
[81] Teerlink JR, Breu V, Sprecher U, et al. Potent vasoconstriction mediated by endothelin ETB receptors in canine coronary arteries. Circ Res, 1994, 74(1): 105-14
[82] Seo B, Oemar BS, Siebenmann R, et al. Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation, 1994, 89(3): 1203-8
[83] Cramer H, Muller-Esterl W, Schroeder C. Subtype-specific endothelin-A and endothelin-B receptor desensitization correlates with differential receptor phosphorylation. J Cardiovasc Pharmacol, 1998, 31(Suppl 1): S203-6
[84] Sanchez R, MacKenzie A, Farhat N, et al. Endothelin B receptor-mediated regulation of endothelin-1 content and release in cultured porcine aorta endothelial cell. J Cardiovasc Pharmacoi, 2002, 39(5): 652-9
[85] Imai T, Hiram Y, Emori T, et al. Induction ofendothelin-1 gene by angiotensin and vasopressin in endothelial cells. Hypertension, 1992, 19(9): 753-757
[86] Lee ME, Bloch KD, Clifford JA, et al. Quertermous T Functional analysis of the endothelin-1 gene promoter. Evidence for an endothelial cell-specific cis-acting sequence.J Biol Chem, 1990, 265(18): 10446-50
[87] Komuro I, Kurihara H, Sugiyama T, et al. Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett, 1988,238(2):249-52
[88] 申景玲，傅松滨，张贵寅．内皮素基因的研究进展．国外医学遗传学分册，2001，24(3)：120
[89] Shichiri M, Adachi S, Sedivy JM, et al. Biphasic Regulation of the Preproendothelin-1 Gene.by c-myc. Endocrinology, 1997, 138(11): 4584-4590
[90] 齐法莲．内皮素及其受体研究与心血管疾病．放射免疫学杂志，2002，15(4)：246-248
[91] Masatsugu K, Itoh H, Chun TH, et al. Shear stress attenuates endothelin and endothelin-converting enzyme expression through oxidative stress. Regul Pept, 2003, 111(1-3):13-9
[92] Wang DL, Wung BS, Peng YC, et al. Mechanical strain increases endothelin-1 gene expression via protein kinase C pathway in human endothelial cells. J Cell Physiol, 1995, 163(2): 400-6
[93] Yakubu MA, Leffler CW. Regulation of ET-1 biosynthesis in cerebral microvascular endothelial cells by vasoactive agents and PKC. Am J Physiol, 1999, 276 (2 Pt 1): C300-5
[94] Uhlmann D, Uhlmann S, Spiegel HU. Endothelin/nitric oxide balance influences hepatic ischemia-reperfusion injury. J Cardiovasc Pharmacol, 2000, 36(5 Suppi 1): S212-4
[95] Tabuchi Y, Nakamaru M, Rakugi H, et al. Effects of endothelin on neuroeffector junction in mesenteric arteries of hypertensive rats. Hypertension, 1990, 15(6 Pt 2): 739-43
[96] Horio T, Kohno M, Yokokawa K, Effect of hypoxia on plasma immunoreactive endothelin-1 concentration in anesthetized rats. Metabolism, 1991, 40(10): 999-1001
[97] Masaki T, Yanagisawa M, Inoue A, et al. Study on the endothelin gene and its expression. Jpn Circ J, 1990, 54(9): 1221-5
[98] Boulanger C, Luscher TF. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J Clin Invest, 1990, 85(2): 587-90
[99] Lepailleur-Enouf D, Valdenaire O, Philippe M, et al. Thrombin induces endothelin expression in arterial smooth muscle cells. Am J Physiol Heart Circ Physiol, 2000, 278(5): H1606-12
[100] 韩正康．家畜生理学(第三版)．中国农业出版社，北京，1996：13
[101] Yoshizumi M, Kurihara H, Morita T, et al. Interleukin 1 increases the production ofendothelin-1 by cultured endothelial cells. Biochem Biophys Res Commun, 1990, 166(1): 324-9
[102] Kurihara H, Yoshizumi M, Sugiyama T, et al. Transforming growth factor-beta stimulates the expression of endothelin mRNA by vascular endothelial cells. Biochem Biophys Res Commun, 1989, 159(3): 1435-40
[103] Aramori I, Nakanishi S. Coupling of two endothelin receptor subtypes to differing signal transduction in transfected Chinese ham ster ovary cells. J Biol Chem, 1992, 267(18): 1246-8
[104] Haynes WG, Waugh CJ, Duckrell MC, et al. Modulators of calcium channels: their effects on endothelin-1 binding to cardiac membranes. J Cardiovasc Pharmacol, 1993, 22(suppl): S 154
[105] Inui T, Ninomiya H, Sasaki Y, et al. Selective activation of excitation-contraction coupling pathways by ETA and ETB receptors in guinea-pig tracheal smooth muscle. British Journal of Pharmacology, 1999, 126(4): 893-902
[106] Gong QY, Yang ZC, Cai H, et al. Effects of endothelin on porcine coronary arterial strips. Zhongguo Yao Li Xue Bao, 1989,10(6): 511-5
[107] Endoh M, Fujita S, Yang HT, et al. Endothelin: receptor subtypes, signal transduction, regulation of Ca~(2+) transients and contractility in rabbit ventricular myocardium. Life Sci, 1998, 62(17-18): 1485-9
[108] Woo SH, Lee CO. Effects ofendothelin-1 on Ca~(2+) signaling in guinea-pig ventricular myocytes: role of protein kinase C. J Mol Cell Cardiol, 1999, 31(3): 631-43
[109] Takenaka T, Epstein M, Forster H, Attenuation of endothelin effects by a chloride channel inhibitor, indanyloxyacetic acid. Am J Physiol, 1992, 262(5 Pt 2): F799-806
[110] Spatz M, Kawai N, Bembry J, et al. Human brain capillary endothelium: modulation of K+ effiux and K+, Ca~(2+) uptake by endothelin. Neurochem Res, 1998, 23(8): 1125-32
[111] Fujitani Y, Ueda H, Okada T, et al. A selective agonist of endothelin type B receptor, IRL 1620, stimulates cyclic GMP increase via nitric oxide formation in rat aorta. J Pharmacol Exp Ther, 1993, 267(2): 683-9
[112] Resink TJ. Inducible endothelin mRNA expression and peptide secretion in cultured human vascular smooth muscle cells. Biochem Biophys REs Commun, 1990, 168:1303～1310
[113] Saito S, Hirata Y, Imai T, et al. Autocrine regulation of the endothelin-1 gene in rat endothelial cells. J Cardiovasc Pharmacol, 1995, 26(Suppl 3): S84-7
[114] Oriji GK, Keiser HR. Protein Kinase C mediates angiotensin 11-induced contractions and the release of Endothelin and prostacyclin in rat aortic rings. Prostaglandins Leukotrienes Essential Fatty Acids, 1997, 57(2): 135
[115] Sharma AC, Motev. SJ, farias S. Sepsis alters myocardial and plasma concentrations of endotheline and nitric oxide in rats. J Mol Cell Cardiol, 1997, 29:1469
[116] Pittet JF, Morel DR, Hemsen A. Elevated plasma endothelin-1 concentrations areas sociated with the severity of illness in patients with sepsis. Ann Surg, 1991, 213:261
[117] Sakurai T, Morimoto H, Kasuya Y, et al. Level of ETB receptor mRNA is down-regulated by endothelins through decreasing the intracellular stability of mRNA molecules. Biochem Biophys Res Commun, 1992, 186(1): 342-7
[118] Roubert P, Gillard V, Plas P, et al. Down-regulation of endothelin binding sites in rat vascular smooth muscle cells. Am J Hypertens, 1990, 3(4): 310-2
[119] Miasiro N, Paiva AC. Homologous desensitization of the effects of endothelin on rabbit aorta rings and on cultured rat aorta smooth muscle cells. Eur J Pharmacol, 1990, 179(1-2): 151-8
[120] Nayler WG, Ou RC, Gu XH, et al. Effect of amlodipine pretreatment on ischaemia-reperfusion-induced increase in cardiac endothelin-1 binding site density. J Cardiovasc Pharmacol, 1992, 20(3): 416-20
[121] Clozel M. Down-regulation of endothelin receptor by autocrine production of endothelin-1. Am J Physiol. 1993, 265(4): C188～C192
[122] de Nucci G, Thomas R, D'Orleans-Juste P, et al. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyelin and endothelium-derived relaxing factor. Proc Natl Acad Sci, U S A 1988,85(24):9797-800
[123] Hinojosa-Laborde C, Lange DL. Endothelin regulation of adrenal function. Clin Exp Pharmacol Physiol, 1999, 26(12): 995-9
[124] Minkes RK, MacMillan LA, Bellan JA, et al. Analysis of regional responses to endothelin in hindquarters vascular bed of cats. Am J Physiol, 1989, 256(2 Pt 2): H598-602
[125] Minkes RK, Higuera TR, Rogers GF, et al. Cardiovascular responses to vasoactive intestinal contractor, a novel endothelin-like peptide. Am J Physiol, 1990, 259(4 Pt 2): H1152-60
[126] Piacentini L, Gray M, Honbo NY, et al. Endothelin-1 stimulates cardiac fibroblast proliferation through activation of protein kinase C. J Mol Cell Cardiol, 2000, 32(4): 565-76
[127] Rosen B, Barg J, Zimlichman R. The effects of angiotensin Ⅱ, endothelin-1, and protein kinase C inhibitor on DNA synthesis and intracellular calcium mobilization in vascular smooth muscle cells from young normotensive and spontaneously hypertensive rats. Am J Hypertens, 1999, 12(12 Pt 1-2): 1243-51
[128] Hafizi S, Allen SP, Goodwin AT, et al. Endothelin-1 stimulates proliferation of human coronary smooth muscle cells via the ET(A) receptor and is co-mitogenic with growth factors. Atherosclerosis, 1999, 146(2): 351-9
[129] Iwasaki H, Eguchi S, Marumo F, et al. Endothelin-1 stimulates DNA synthesis of vascular smooth-muscle cells through transactivation of epidermal growth factor receptor. J Cardiovasc Pharmacol, 1998, 31 (Suppl 1): S182-4
[130] Ouchi Y, Kim S, Souza AC, et al. Central effect of endothelin on blood pressure in conscious rats. Am J Physiol, 1989, 256(6 Pt 2): H1747-51
[131] Shichiri M, Hirata Y, Kanno K, et al. Effect of endothelin-1 on release of arginine-vasopressin
from perifused rat hypothalamus. Biochem Biophys Res Commun, 1989, 163(3): 1332-7
[132] Zhang M, Olsson Y. Reactions of astrocytes and microglial cells around hematogenous metastases of the human brain. Expression of endothelin-like immunoreactivity in reactive astrocytes and activation ofmicroglial cells. J Neurol Sci, 1995, 134(1-2): 26-32
[133] Takagi M, Tsukada H, Matsuoka H, Inhibitory effect of endothelin on renin release in vitro. Am J Physiol, 1989, 257(6 Pt 1): E833-8
[134] Munter K, Hackenthal E. The effects ofendothelin on renovascular resistance and renin release. J Hypertens Suppl, 1989, 7(6): S276-7
[135] Matsumura Y, Nakase K, Ikegawa R, et al. The endothelium-derived vasoconstrictor peptide endothelin inhibits renin release in vitro. Life Sci, 1989, 44(2): 149-57
[136] Cozza EN, Gomez-Sanchez CE, Foecking MF, et al. Endothelin binding to cultured calf adrenal zona glomerulosa cells and stimulation of aldosterone secretion. J Clin Invest, 1989, 84(3): 1032-5
[137] Gellai M, DeWolf R, Pullen M, et al. Distribution and functional role of renal ET receptor subtypes in normotensive and hypertensive rats. Kidney Int, 1994, 46(5): 1287-94
[138] Polak K, Luksch A, Frank B, Regulation of human retinal blood flow by endothelin-1. Exp Eye Res, 2003, 76(5): 633-640
[139] Kawamura H, Oku H, Li Q, et al. Endothelin-induced changes in the physiology of retinal pericytes. Invest Ophthalmol Vis Sci, 2002, 43(3): 882-8
[140] Dashwood MR, Timm M, Kaski JC. Regional variations in ETA/ETB binding sites in human coronary vasculature. J Cardiovasc Pharmacol, 1995, 26(Suppl 3): S351-4
[141] Yamazaki T, Komuro I, Kudoh S, et al. Endothelin-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy. J Biol Chem, 1996, 271(6): 3221-8
[142] Sakai S, Miyauchi T, Sakurai T, et al. Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure. Marked increase in endothelin-1 production in the failing heart. Circulation, 1996, 93(6): 1214-22
[143] Bobik A, Grooms A, Millar JA, Growth factor activity of endothelin on vascular smooth muscle. Am J Physiol, 1990, 258(3 Pt 1): C408-15
[144] Timm M, Kaski JC, Dashwood MR. Endothelin-like immunoreactivity in atherosclerotic human coronary arteries. J Cardiovasc Pharmacol, 1995, 26(Suppl 3): S442-4
[145] Kobayashi T, Miyauchi T, Sakai S, et al. Expression of endothelin-1, ETA and ETB receptors, and ECE and distribution of endothelin-1 in failing rat heart. Am J Physiol, 1999, 276(4 Pt 2): H1197-206
[146] Li H, Chen SJ, Chen YF, et al. Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia. J Appl Physiol, 1994, 77(3): 1451-9
[147] Kitsukawa Y, Gu ZF, Hildebrand P, et al. Gastric smooth muscle cells possess two classes of endothelin receptors but only one alters contraction. Am J Physioi, 1994, 266(4 Pt 1): G713-21
[148] Lazaratos S, Kashimura H, Nakahara A, et al, Gastric ulcer induced by submucosal injection of
ET-1: role of potent vasoconstriction and intraluminal acid. Am J Physiol, 1993, 265(3 Pt 1): G491-8
[149] Masuda E, Kawano S, Michida T, et al. Plasma and gastric mucosal endothelin-1 concentrations in patients with peptic ulcer. Dig Dis Sci, 1997, 42(2): 314-8
[150] Khan MA, Dashwood MR, Mumtaz FH, et al. Upregulation of endothelin A receptor sites in the rabbit diabetic kidney: potential relevance to the early pathogenesis of diabetic nephropathy. Nephron, 1999, 83(3): 261-7
[151] Dashwood MR, Timm M, Muddle JR, et al. Regional variations in endothelin-1 and its receptor subtypes in human coronary vasculature: pathophysiologicai implications in coronary disease. Endothelium, 1998, 6(1): 61-70
[152] Xu SW, Denton CP, Dashwood MR, et al. Endothelin-1 regulation of intercellular adhesion molecule-1 expression in normal and sclerodermal fibroblasts. J Cardiovasc Pharmacoi, 1998, 31(Suppl 1): S545-7
[153] Watanabe T, Suzuki N, Shimamoto N, et al. Contribution of endogenous endothelin to the extension of myocardial infarct size in rats. Circ Res, 1991, 69(2):370-7
[154] Watanabe T, Suzuki N, Shimamoto N, et al. Endothelin in myocardial infarction. Nature 1990, 344(62): 114
[155] Saijonmaa O, Ristimaki A, Fyhrquist F. Atrial natriuretic peptide, nitroglycerine, and nitroprusside reduce basal and stimulated endothelin production from cultured endothelial cells. Biochem Biophys Res Commun, 1990, 173(2): 514-20
[156] Urakami A, Todo S, Zhu Y, et al. Attenuation of ischemic liver injury by monoclonal anti-endothelin antibody, AwETN40. J Am Coll Surg, 1997, 185(4): 358-64
[157] Deng LY, Schiffrin EL. Effect of antihypertensive treatment on response to endothelin of resistance arteries of hypertensive rats. J Cardiovasc Pharmacol, 1993,21(5):725-31
[158] McMahon EG, Palomo MA, Brown MA, et at. Effect of phosphoramidon (endothelin converting enzyme inhibitor) and BQ-123 (endothelin receptor subtype A antagonist) on blood pressure in hypertensive rats. Am J Hypertens, 1993, 6(8): 667-73
[159] Matsuura A, Okumura H, Ashizawa N, et al. Big endothelin-1-induced sudden death is inhibited by phosphoramidon in mice. Life Sci, 1992, 50(21): 1631-8
[160] Matsumura Y, Ikegawa R, Suzuki Y, Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: the relationship to endothelin-1 levels in the cerebrospinai fluid. Life Sci, 1991, 49(11): 841-8
[161] Ihara M, Noguchi K, Saeki T, et al. ioiogical profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci, 1992; 50(4): 247-55
[162] 张建伟．内皮素拮抗剂研究进展．国外医学生理、病理科学与临床分册，1997，17(4)：349-350
[163] Stewart DJ, Levy RD, Cemacek P, et al. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med, 1991, 114(6): 464-9 ; ::
[164] Dupuis J, Stewart DJ, Cernacek P, et al. Human pulmonary circulation is an important site for both clearance and production of endothelin-1. Circulation, 1996, 94(7): 1578-84
[165] Kohno M, Yasunari K, Murakawa K, et al. Plasma immunoreactive endothelin in essential hypertension. Am J Med, 1990, 88(6): 614-8
[166] 冉丕鑫，徐军，陈顺存，等．慢性缺氧对大鼠肺动脉和右心室内皮素与一氧化氮合成酶mRNA表达的影响．中华医学杂志，1995，75(8)：479
[167] 冉丕鑫，徐军，陈顺存，等．慢性缺氧影响肺脏内皮素和一氧化氮成酶mRNA的表达[J]．中国病理生理杂志，1997，13(1)：35
[168] 冉丕鑫，杜志强，陈颜芳，等．内皮素对离体肺动脉及肺动脉平滑肌细胞的作用．中国动脉硬化杂志，2000，8(2)：151-153
[169] Filep JG. Endothelin peptides: biological actions and pathophysiological significance in the lung. Life Sci, 1993; 52(2): 119-33
[170] Homma S, Maclean MR, McCulloch KM, etal. Endotheline ETA-and ETB-receptor mediated vasoconstriction in rat pulmonary arteries and arterioles. J Cardiovasc pharmacol, 1994, 23: 838
[171] Viossat I, Chapelat M, Chabrier PE, Validation of radioimmunoassay of tissue and plasma endothelin-1. Arch Mal Coeur Vaiss, 1990, 83(8): 1263-5
[172] Cassin S, Kristova V, Davis T, et al. Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ. J Appl Physiol, 1991, 70(3): 1228-34
[173] Nakamichi K, Ihara M, Kobayashi M, et al. Different distribution of endothelin receptor subtypes in pulmonary tissues revealed by the novel selective ligands BQ-123 and [Alal,3,11,15]ET-1. Biochem Biophys Res Commun, 1992, 182(1): 144-50
[174] Goldie RG, D'Aprile AC, Self GJ, et al. The distribution and density of receptor subtypes for endothelin-1 in peripheral lung of the rat, guinea-pig and pig. Br J Pharmacol, 1996, 117(4): 729-35
[175] Ryan US.Receptors on pulmonary endothelial cells. Am Rev Respir Dis, 1990,141(3 Pt 2):S 132-6
[176] MacLean MR, McCulloch KM, Baird M. Endothelin ETA- and ETB-receptor-mediated vasoconstriction in rat pulmonary arteries and arterioles. J Cardiovasc Pharmacol, 1994, 23(5): 838-45
[177] Takahashi H, Soma S, Muramatsu M, et al. Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery. Eur Respir J, 2001, 18(1): 5-14
[178] Takahashi H, Soma S, Muramatsu M, et al. Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions. Am J Physiol Lung Cell Mol Physiol, 2001,280(6): L1104-14
[179] Sudjarwo SA, Hori M, Takai M, et at. A novel subtype of endothelin B receptor mediating contraction in swine pulmonary vein. Life Sci, 1993, 53(5): 431-7
[180] 王玉玮．内皮素代谢及其与肺血管病变的关系．医学综述，1995，1(10)：447-449
[181] Guarda E, Katwa LC, Myers PR, et al. Effects of endothelins on collagen tumover in cardiac fibroblasts. Cardiovasc Res, 1993, 27(12): 2130-4
[182] Mallat A, Fouassier L, Preaux AM, et al. Growth inhibitory properties of endothelin-1 in human hepatic myofibroblastic Ito cells. An endothelin B receptor-mediated pathway. J Clin Invest, 1995, 96(1): 42-9
[183] Murlas CG, Gulati A, Singh G, et al. Endothelin-1 stimulates proliferation of normal airway epithelial cells. Biochem Biophys Res Commun, 1995, 212(3): 953-9
[184] Takimoto M, Oda K, Sasaki Y, et al. Endothelin-A receptor-mediated prostanoid secretion via autocrine and deoxyribonucleic acid synthesis via paracrine signaling in human bronchial epithelial cells. Endocrinology. 1996, 137(11): 4542-50
[185] Filep JG, Battistini B, Sirois P. Induction by endothelin-1 of epithelium-dependent relaxation of guinea-pig trachea in Vitro: role for nitric oxide. Br J Pharmacol, 1993, 109(3): 637-44
[186] Michael JR, Markewitz BA. Endothelins and the lung. Am J Respir Crit Care Med, 1996, 154(3 Pt 1): 555-81
[187] Markewitz BA, Kohan DE, Michael JR. Endothelin-1 synthesis, receptors, and signal transduction in alveolar epithelium: evidence for an autocrine role, Am J Physiol, 1995, 268(2 Pt 1): L192-200
[188] Tamaoki J, Kanemura T, Sakai N, et al. Endothelin stimulates ciliary beat frequency and chloride secretion in canine cultured tracheal epithelium. Am J Respir Cell Mol Biol, 1991, 4(5): 426-31
[189] Horgan MJ, Pinheiro JM, Malik AB. Mechanism of endothelin-1-induced pulmonary vasoconstriction. Circ Res, 1991, 69(1): 157-64
[190] Ishikawa T, Yanagisawa M, Kimura S, et al. Positive chronotropic effects of endothelin, a novel endothelium-derived vasoconstrictor peptide. Pflugers Arch, 1988, 413(1): 108-10
[191] Maguire JJ, Davenport AP. ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro. Br J Pharmacol, 1995,115(1):191-7.
[192] Toga H, Ibe BO, Raj JU. In vitro responses of ovine intrapuimonary arteries and veins to endothelin-1. Am J Physiol, 1992, 263(1 Pt 1): L15-21
[193] Zellers TM, McCormick J, Wu Y. Interaction among ET-1, endothelium-derived nitric oxide, and prostacyclin in pulmonary arteries and veins. Am J Physiol, 1994,267(1 Pt 2): H139-47
[194] 郭光伟．内皮素与心肺血管系统．山西临床医药杂志，1997，6(1)：1-3
[195] Hasleton PS, Heath D, Brewer DB. Hypertensive pulmonary vascular disease in states of chronic hypoxia. J Pathol Bacteriol, 1968, 95(2): 431-40.
[196] Heath D, Segel N, Bishop J. Pulmonary veno-occlusive disease. Circulation, 1966, 34(2): 242-8
[197] Rabinovitch M, Bothwell T, Hayakawa BN, et al. Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension. A correlation of light with scanning electron microscopy and transmission electron microscopy. Lab Invest, 1986, 55(6): 632-53
[198] Hung KS, McKenzie JC, Mattioli L, et al. Scanning electron microscopy of pulmonary vascular endothelium in rats with hypoxia-induced hypertension. Acta Anat (Basel), 1986,126(1):13-20
[199] 林春龙，张珍祥，徐永健，等．慢性阻塞性肺病患者内皮素-1 水平与肺血流动力学的关系．中国现代医学杂志，1998，8(1)：17-21
[200] 石云，杜军保，汤秀英，等．慢性缺氧性肺动脉高压大鼠肺血管显微结构研究 实用儿科临床杂志，2002，17(1)：1-4
[201] Dzau VJ, Gibbons GH. Endothelium and growth factors in vascular remodeling of hypertension. Hypertension, 1991, 18(5 Suppl): Ⅲ115-21
[202] Barer GR, Cai YN, Russell PC, et al. Reactivity and site of vasomotion in pulmonary vessels of chronically hypoxic rats: relation to structural changes. Am Rev Respir Dis, 1989, 140(5): 1483-5
[203] 陈光喜，王小龙，黄克和．肉鸡腹水综合征的临床病理学研究．中国兽医杂志，1996，22(12)：10-11
[204] 高洪．高原地区肉鸡腹水症病理形态学观察．中国兽医科技，1996，26(11)：35-36
[205] 何诚，贾君镇，高娃，等．肉鸡腹水症发病机理研究：低温处理后肉鸡肺脏超微结构的病理学变化．电子显微学报，2002，21(2)：192-195
[206] 王世英，张登荣，张登岭，等．肉鸡腹水症心肝肺显微和超微结构研究．中国兽医学报，1997，17(3)：292-293
[207] Yoshibayashi M, Nishioka K, Nakao K, et al. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation. Circulation, 1991, 84(6): 2280-5
[208] Chen W, Cheng D. Effects of endothelin receptor antagonist on the hypoxic pulmonary hypertension. Hua Xi Yi Ke Da Xue Xue Bao, 2000, 31(3): 370-2, 386
[209] Yang X, Chen W, Li F. The change and distribution of endothelin-1 in lung of hypoxic pulmonary hypertension rat. Hua Xi Yi Ke Da Xue Xue Bao, 2000,31(1):30-3
[210] 王秋月，李尔然，赵桂喜．老年肺心病患者血浆内皮素-1与肺血流动力学的关系．中国老年学杂志，1998，18：55-56
[211] Stelzner TJ, O'Brien RF, Yanagisawa M, et al. Increased lung endothelin-1 production in rats with idiopathic pulmonary hypertension. Am J Physiol, 1992, 262(5 Pt 1): L614-20
[212] Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med, 1993,328(24): 1732-9
[213] Allen SW, Chatfield BA, Koppenhafer SA, et al. Circulating immunoreactive endothelin-1 in children with pulmonary hypertension. Association with acute hypoxic pulmonary vasoreactivity. Am Rev Respir Dis, 1993,148(2): 519-22
[214] Kourembanas S, Marsden PA, McQuillan LP, et al. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J Clin Invest, 1991, 88(3): 1054-7
[215] Elton TS, Oparil S, Taylor GR. Normobaric hypoxia stimulates endothelin-1 gene expression in the rat. Am J Physiol, 1992, 263(6 Pt 2): R1260-4
[216] Li H, Elton TS, Chen YF, et al. Increased endothelin receptor gene expression in hypoxic rat lung. Am J Physiol 1994, 266(5 Pt 1): L553-60
[217] 刘绪万．内皮素与肺动脉高压．国外医学儿科学分册，1995，22(6)：289-292
[218] Goresky CA, Foumier A. Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors. J Appl Physiol, 1996, 81 (4): 1510-5
[219] Wort SJ, Woods M, Warner TD, et al. Endogenously Released Endothelin-1 from Human Pulmonary Artery Smooth Muscle Promotes Cellular Proliferation. Am. J. Respir. Cell Mol. Biol, 2001, 25(1): 104-110
[220] Chen SJ, Chen YF, Opgenorth TJ, et al. The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in Sprague-Dawley rats. J Cardiovasc Pharmacol, 1997, 29(6): 713-25
[221] Givertz MM, Colucci WS, LeJemtel TH, et al. Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation, 2000, 101(25): 2922-7
[222] Coe Y, Haleen SJ, Welch KM, et al. The endothelin-A-receptor antagonist PD 180988 (CI-1034) selectively reverses the pulmonary vasoconstrictor response to hypoxia in the lamb. J Cardiovasc Pharmacol, 2000, 36(5 Suppl 1): S331-3
[223] Franco-Cereceda A, Holm P. Selective or nonselective endothelin antagonists in porcine hypoxic pulmonary hypertension? J Cardiovasc Pharmacol, 1998, 31(Suppl 1): S447-52
[224] Montagnani M, Vulpis V, Nazzaro P, et al. Endothelin-1-receptor-mediated responses in resistance vessels of young and adult spontaneously hypertensive rats. J Hypertens, 2000,18(7): 893-900
[225] 郝春荣，熊密，王迪浔，等．低氧诱导因子-1α和内皮素-1基因在大鼠低氧性肺动脉高压中的表达．中华病理学杂志，2002，31(2)：140-142
[226] Zamora MA, Dempsey EC, Walchak SJ, et al. BQ123, an ETA receptor antagonist, inhibits endothelin-1-mediated proliferation of human pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol, 1993, 9(4): 429-33
[227] Soma S, Takahashi H, Muramatsu M, et al. Localization and distribution of endothelin receptor subtypes in pulmonary vasculature of normal and hypoxia-exposed rats. Am J Respir Cell Mol Biol, 1999, 20(4): 620-30
[228] Li H, Elton TS, Chen YF, et al. Increased endothelin receptor gene expression in hypoxic rat lung. Am J Physiol, 1994, 266(5 Pt 1): L553-60
[229] Davie N, Haleen SJ, Upton P, et al. ET_A and ET_B Receptors Modulate the Proliferation of Human Pulmonary Artery Smooth Muscle Cells. Am. J. Respir. Crit. Care Med., 2002, 165(3): 398-405
[230] Ivy DD, Yanagisawa M, Gariepy CE, et al. Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats. Am J Physiol Lung Cell Mol Physiol, 2002,282(4):L703-t2
[231] 贾建锋，杜军保，齐建光．大内皮素-1的生物转化对兔肺动脉收缩反应的影响．中华医学杂志，1999，79(8)：632-634
[232] Hasunuma K, Rodman DM, O'Brien RF, et al. Endothelin 1 causes pulmonary vasodilation in rats. Am J Physiol, 1990, 259(1 Pt 2): H48-54
[233] Nagase T, Fukuchi Y, Matsui H, et al. In vivo effects of endothelin A-and B-receptor antagonists in guinea pigs. Am J Physiol, 1995, 268(5 Pt 1): L846-50
[234] Pons F, Loquet I, Touvay C, et al. Comparison of the bronchopulmonary and pressor activities of endothelin isoforms ET-1, ET-2, and ET-3 and characterization of their binding sites in guinea pig lung. Am Rev Respir Dis, 1991, 143(2): 294-300
[235] Noguchi S, Kashihara Y, Bertrand C. The induction of a biphasic bronchospasm by the ETB agonist, IRL 1620, due to thromboxane A2 generation and endothelin-1 release in guinea-pigs. Br J Pharmacol, 1996, 118(6): 1397-402
[236] Katoh H, Terada H, Iimuro M, et al. Heterogeneity and underlying mechanism for inotropic action ofendothelin-1 in rat ventricular myocytes. Br J Pharmacol, 1998, 123(7): 1343-50
[237] Zamora MR, Stelzner TJ, Webb S, et al. Overexpression ofendothelin-1 and enhanced growth of pulmonary artery smooth muscle cells from fawn-hooded rats. Am J Physiol, 1996, 270(1 Pt 1): L101-9
[238] Hahn AW, Regenass S, Resink TJ, et al. Morphogenic effects of endothelin-1 on vascular smooth muscle cells. J Vase Res, 1993,30(4): 192-201
[239] Mansoor AM, Honda M, Saida K, et al. Endothelin induced collagen remodeling in experimental pulmonary hypertension. Biochem Biophys Res Commun, 1995, 215(3): 981-6
[240] Dawes KE, Peacock AJ, Gray AJ, et al. Characterization of fibroblast mitogens and chemoattractants produced by endothelial cells exposedto hypoxia. Am J Respir Cell Mol Biol, 1994, 10(5): 552-9
[241] Filep JG, Battistini B, Sirois P. Pharmacological modulation of endothelin-induced contraction of guinea-pig isolated airways and thromboxane release. Br J Pharmacol, 1991, 103(3): 1633-40
[242] Kovacs EJ, DiPietro LA. Fibrogenic cytokines and connective tissue production. FASEB J, 1994, 8(11): 854-61
[243] Battistini B, Chailler P, D'Orleans-Juste P, et al. Growth regulatory properties of endothelins. Peptides, 1993, 14(2): 385-99
[244] 乔健，董世山，乔惠理，等．右心导管法直接测定肉仔鸡肺动脉压．中国农业大学学报，1998，3(3)：117-118
[245] 杨小东，陈文彬，陈俊杰．内皮素在低氧性肺动脉高压大鼠肺内表达和水平变化的研究．中华内科杂志，1996，35(11)：734-737
[246] Zoccali C, Leonardis D, Parkongo S, et al. Urinary and plasma endothelin-1 in essential hypertension and in hypertension secondary to renoparenchyma disease. Nephrol Dial Transplant, 1995, 10(8): 1320
[247] 唐轶，崔志澄．内皮素与血管内皮舒张因子的相互调节和作用关系．北京医学，1998，20(1)：35-37
[248] Iscon TC, Vaclav H, Kenneth E, et al. Increased endotheliun-derived NO in hypertensive pulmonary circulation of chronically hypoxic Rats. J Appl Physiol, 1994, 76(2): 933
[249] 汤健，唐朝枢，杨军，等．内皮素．北京医科大学、中国协和医科大学联合出版社，1994，163-164，224
[250] Salvati P, Chierchia S, DhoL, etal. Proarrhythmic activity of intra-coronary endothelin in dogs; sedation to the site of administration and to changes inregional flow. J Cardiovasc Pharmacol, 1991, 17(6): 1007-1014
[251] 汤健，杨青，张继峰．环五肽BQ123对内皮素-1的拮抗效应．北京医科大学学报，1992，24(6)：431-434
[252] Leite-Moreira AF, Bras-Silva C, Pedrosa CA, et al. ET-1 increases distensibility of acutely loaded myocardium: a novel ETA and Na~+/H~+ exchanger-mediated effect. Am J Physiol Heart Circ, 2003, 284(4): H1332-9
[253] Goraca A. Negative chronotropic effect of endothelin-1 (ET-1) in the cardiac pacemaker tissue. J Physiol Pharmacol, 2003, 54(1): 53-63
[254] 姚平，潘敬远，詹澄扬．内皮素对成年离体心室肌细胞内游离浓度的影响及机制．中国病理生理杂志，1995，15(4)：18-22
[255] 程德云，陈文彬，肖欣荣．Cromakalim阻断内皮素-1介导肺动脉高压的研究．华西医科大学学报，1998，29(1)：79-81
[256] Rizzoni D, Porteri E, Piccoli A, et al. The vasoconstriction induced by endothelin-1 is mediated only by ET(A) receptors in mesenteric small resistance arteries of spontaneously hypertensive rats and Wistar Kyoto rats. J Hypertens, 1997, 15(12 Pt 2): 1653-7
[257] Danthuluri NR, Brock TA. Endothelin receptor-coupling mechanisms in vascular smooth muscle: a role for protein kinase C. J Pharmacol Exp Ther, 1990, 254(2): 393-9
[258] Hubel CA, Highsmith RF. Endothelin-induced changes in intracellular pH and Ca2+ in coronary smooth muscle: role of Na(+)-H+ exchange. Biochem J, 1995, 310 (Pt 3): 1013-20
[259] Saito Y, Nakao K, Itoh H, et al. Endothelin in human plasma and culture medium of aortic endothelial cells detection and characterization with radioimmunoassay using monoclonal antibody. Biochem Biophys Res Commun, 1989, 161(1): 320-6
[260] Koshi T, Torii T, Ami K, et al. Inhibition of endothelin (ET)-1-and ET-2-induced vasoconstriction by anti-ET-1 monoclonal antibody. Chem Pharm Bull (Tokyo), 1991, 39(5): 1295-7
[261] White DG, Cannon TR, Garratt H, et al. Endothelin ETA and ETB receptors mediate vascular smooth-muscle contraction. J Cardiovasc Pharmacol, 1993, 22 (Suppl8): S 144～148.
[262] Schuize-Neick I, Li J, Reader JA, et al. The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease. J Thorac Cardiovasc Surg, 2002, 124(3): 435-41.
[263] Bonvallet S. T, Oka M, Yano M, et al. BQ123, an ETA receptor antagonist, attenuates endothelin-1-induced vasoconstriction in rat pulmonary circulation. J Cardiovasc Pharmacol, 1993, 22(1): 39-43.
[264] Münter K, Ehmke H, Kirchengast M. Maintenance of blood pressure in normotensive dogs by endothelin. Am J Physiol Heart Cire Physiol, 1999, 276(3): H1022-H1027
[265] Reinhart GA, Preusser LC, Opgenorth TJ, et al. Endothelin and ETA receptors in long-term arterial pressure homeostasis in conscious nonhuman primates. Am J Physiol Regul Integr Comp Physiol, 2000, 279(5): R1701-R1706
[266] Warner TD, Allcock GH, Vane JR. Reversal of established responses to endothelin-1 in vivo and in vitro by the endothelin receptor antagonists, BQ-123 and PD 145065. Br J Pharmacol, 1994, 112(1): 207-13
[267] Owe-Young R, Schyvens CG, Qasabian RA, et al. Transcriptional down-regulation of the rabbit pulmonary artery endothelin B receptor during phenotypic modulation. Br J Pharmacol, 1999, 126(1): 103-10
[268] Ito H, Hiroe M, Hirata Y, Fujisaki H, et al. Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload. Circulation, 1994, 89(5): 2198-203
[269] Kawai N, Yamamoto T, Yamamoto H, et al. Functional characterization of endothelin receptors on cultured brain capillary endothelial cells of the rat. Neurochem, 1997, 31(4): 597-605
[270] 王金勇，王小龙，向瑞萍，等．环境低温和T_3对肉鸡内皮素、一氧化氮和肺动脉压的影响．中国兽医学报，2002，22(5)：509-511
[271] 何诚．肉鸡腹水症发病机理研究：低温环境对肉鸡心功能、肺动脉高压的影响及其机制探讨：[博士学位论文]．北京：2001：47
[272] Criscione L, Thomann H, Luu TD. Sensitivity and reactivity to endothelin-1 in mesenteric beds and aortic rings of 4-week-old spontaneously hypertensive rats. Clin Exp Hypertens, 1992, 14(3): 453-67
[273] Tomobe Y, Ishikawa T, Yanagisawa M, et al. Mechanisms of altered sensitivity to endothelin-1 between aortic smooth muscles of spontaneously hypertensive and Wistar-Kyoto rats. J Pharmacol Exp Ther, 1991, 257(2):555-61
[274] Clozel M. Endothelin sensitivity and receptor binding in the aorta of spontaneously hypertensive rats. Hypertens, 1989, 7(11): 913-7
[275] Touyz RM, Deng LY, Li JS, et al. Differential effects of vasopressin and endothelin-1 on vascular contractile and calcium responses in pressurized small arteries from spontaneously hypertensive rats. J Hypertens, 1996, 14(8):983-91
[276] Roberts-Thomson P, McRitchie RJ, Chalmers JP. Experimental hypertension produces diverse changes in the regional vascular responses to endothelin-1 in the rabbit and the rat. J Hypertens, 1994, 12(11): 1225-34
[277] Oparil S, Chen SJ, Meng QC, Elton TS, et al. Endothelin-A receptor antagonist prevents acute hypoxia-induced pulmonary hypertension in the rat. Am J Physiol, 1995, 268(1 Pt 1): L95-100
[278] Balyakina EV, Chen D, Lawrence ML, et al. ET-1 receptor gene expression and distribution in L1 and L2 cells from hypertensive sheep pulmonary artery. Am J Physiol Lung Cell Mol Physiol, 2002, 283(1): L42-51
[279] wideman R F Jr, Ismail M,Kirby Y K, et al. Furosemide reduces the incidence of pulmonary hypertension syndrome (ascites) in broilers exposed to cool environmental temperatures. Poult Sci, 1995, 74(2): 314-322
[280] 董世山，乔健，栗少文，等．肺动脉高压与肉鸡腹水综合征发生发展的关系．畜牧兽医学报，2000，31(4)：325-330
[281] MacLean, MR. Endothelin-1: a mediator of pulmonary hypertension? Pulm Pharmacol Ther, 1998, 11(2): 125-132
[282] Janakidevi, K, Fisher MA, Del Vecchio PJ, et al. Endothelin-1 stimulates DNA synthesis and proliferation of pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol, 1992, 263: C1295-C1301
[283] Matsuura A, Yamochi W, Hirata K, et al. Stimulatory interaction between vascular endothelial growth factor and endothelin-1 on each gene expression. Hypertension, 1998, 32(1):89-95
[284] Peifley KA, Winkles JA. Angiotensin Ⅱ and endothelin-1 increase fibroblast growth factor-2 mRNA expression in vascular smooth muscle cells. Biochem Biophys Res Commun, 1998, 242(1): 202-8
[285] 张丽萍，范英群，曾强，等．卡托普利及抗内皮素抗体对自发性高血压大鼠血压的急性作用．解放军医学杂志，1996，21(3)：205-6
[286] 林江凯，王宪荣．内皮素在神经源性肺水肿中的意义．中华实验外科杂志，1996，13(6)：365-6
[2] Gillespie MN, Owasoyo JO, McMurtry IF, et al. Sustained coronary vasoconstriction provoked by a peptidergic substance released from endothelial cells in culture. J Pharmacol Exp Ther, 1986, 236(2): 339-43
[3] O'Brien RF, Robbins RJ, McMurtry IF. Endothelial cells in culture produce a vasoconstrictor substance. J Cell Physiol, 1987, 132(2): 263-70
[4] Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988,332(6163):411-5
[5] Yanagisawa M, Inoue A, Ishikawa T, et al. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc.Natl Acad Sci, U S A 1988, 85(18): 6964-7
[6] Itoh Y, Yanagisawa M, Ohkubo S, et al. Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: identity of human and porcine endothelin. FEBS Lett, 1988, 231(2): 440-4
[7] Tomobe Y, Miyauchi T, Saito A, Yanagisawa M, Kimura S, Goto K, Masaki T. Effects of endothelin on the renal artery from spontaneously hypertensive and Wistar Kyoto rats. Eur J Pharmacol. 1988, 152(3): 373-4
[8] Hirata Y, Yoshimi H, Takata S, et al. Cellular mechanism of action by a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells. Biochem Biophys Res Commun, 1988, 154(3): 868-75
[9] Fukuda Y, Hirata Y, Yoshimi H, et al. Endothelin is a potent secretagogue for atrial natriuretic peptide in cultured rat atrial myocytes. Biochem Biophys Res Commun, 1988,155(1): 167-72
[10] Yanagisawa M, Inoue A, Ishikawa T, et al. Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc Natl Acad Sci, U S A 1988, 85(18): 6964-7
[11] Uchida Y, Ninomiya H, Saotome M, et al. Endothelin, a novel vasoconstrictor peptide, as potentbronchoconstrictor. Eur J Pharmacol, 1988,154(2):227-8
[12] Chander CL, Moore AR, Desa FM, et al. The local modulation of vascular permeability by endothelial cell derived products. J Pharm Pharmacol, 1988, 40(10): 745-6
[13] Wiklund NP, Ohlen A, Cederqvist B. Inhibition of adrenergic neuroeffector transmission by endothelin in the guinea-pig femoral artery. Acta Physiol Scand, 1988, 134(2): 311-2
[14] Auguet M, Delaflotte S, Chabrier PE, et al. Endothelin and Ca~(++) agonist Bay K 8644: different vasoconstrictive properties. Biochem Biophys Res Commun, 1988, 156(1): 186-92
[15] Kloog Y, Ambar I, Sokolovsky M, et al. Sarafotoxin, a novel vasoconstrictor peptide:
phosphoinositide hydrolysis in rat heart and brain. Science, 1988, 242(4876): 268-70
[16] Firth JD, Ratcliffe PJ, Raine AE, et al, Endothelin: an important factor in acute renal failure? Lancet, 1988, 2(8621): 1179-82
[17] Goetz KL, Wang BC, Madwed JB, et al. Cardiovascular, renal, and endocrine responses to intravenous endothelin in conscious dogs. Am J Physiol, 1988, 255(6 Pt 2): R1064-8
[18] Van Renterghem C, Vigne P, Barhanin J, et al. Molecular mechanism of action of the vasoconstrictor peptide endothelin. Biochem Biophys Res Commun, 1988, 157(3): 977-85
[19] Resink TJ, Scott-Burden T, Buhler FR. Endothelin stimulates phospholipase C in cultured vascular smooth muscle cells. Biochem Biophys Res Commun, 1988, 157(3): 1360-8
[20] Brain SD, Tippins JR, Williams TJ. Endothelin induces potent microvascular constriction. Br J Pharmacol, 1988, 95(4): 1005-7
[21] Kimura S, Kasuya Y, Sawamura T, Shinmi O, et al. Structure-activity relationships of endothelin: importance of the C-terminal moiety. Biochem Biophys Res Commun. 1988, 156(3): 1182-6
[22] Kumagaye S, Kuroda H, Nakajima K, et al. Synthesis and disulfide structure determination of porcine endothelin: an endothelium-derived vasoconstricting peptide. Int J Pept Protein Res, 1988, 32(6): 519-26
[23] Nakajima K, Kumagaye S, Nishio H, et al. Synthesis of endothelin-1 analogues, endothelin-3, and sarafotoxin S6b: structure-activity relationships. J Cardiovasc Pharmacol, 1989,13 (Suppl 5):S8-12
[24] Nayler WG, Gu XH, Casley DJ. Sarafotoxin S6c is a relatively weak displacer of specifically bound 125I-endothelin. Biochem Biophys Res Commun, 1989, 161(1): 89-94
[25] Bdolah A, Wollberg Z, Fleminger G, et al. SRTX-d, a new native peptide of the endothelin/sarafotoxin family. FEBS Lett, 1989, 256(1-2): 1-3
[26] Inoue A, Yanagisawa M, Kimura S, et al. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci, U S A 1989,86(8):2863-7
[27] Saida K, Mitsui Y, Ishida N. A novel peptide, vasoactive intestinal contractor, of a new (endothelin) peptide family. Molecular cloning, expression, and biological activity. J Biol Chem, 1989, 264(25): 14613-6
[28] Kishi F, Minami K, Okishima N, Novel 31-amino-acid-length endothelins cause constriction of vascular smooth muscle. Biochem Biophys Res Commun, 1998, 248(2): 387-90
[29] Kido T, Sawamura T, Masaki T. The processingpathway of endothelin-1 production. J Cardiovasc Pharmacol, 1998, 31(Suppl 1): S13-5
[30] Kido T, Sawamura T, Hoshikawa H, et al. Processing of proendothelin-1 at the C-terminus of big endothelin-1 is essential for proteolysis by endothelin-converting enzyme-1 in vivo. Eur J Biochem, 1997, 244(2): 520-6
[31] Bloch KD, Eddy RL, Shows TB, et al. cDNA cloning and chromosomal assignment of the gene encoding endothelin 3. J Bioi Chem, 1989, 264(30): 18156-61
[32] Inoue A, Yanagisawa M, Takuwa Y, et al. The human preproendothelin-1 gene. Complete nucleotide sequence and regulation of expression. J Biol Chem, 1989, 264(25): 14954-9
[33] Yanagisawa M, Inoue A, Takuwa Y, et al. The human preproendothelin-1 gene: possible regulation by endothelial phosphoinositide turnover signaling. J Cardiovasc Pharmacol, 1989, 13 (Suppl 5): S13-7
[34] Chart TS, Lin CX, Chan WY, et al. Mouse preproendothelin-1 gene. cDNA cloning, sequence analysis and determination of sites of expression during embryonic development. Eur J Biochem, 1995, 234(3): 819-26
[35] Denault JB, Claing A, D'Orleans-Juste P, et al. Processing of proendothelin-1 by human furin convertase. FEBS Lett, 1995, 362(3): 276-80
[36] Blals V, Fugere M, Denault JB, Processing of proendothelin-1 by members of the subtilisin-like pro-protein convertase family. FEBS Lett, 2002, 524(1-3): 43-8
[37] Hirata Y, Matsunaga T, Ando K, et al. Presence of endothelin-1-like immunoreactivity in human cerebrospinal fluid. Biochem Biophys Res Commun, 1990, 166(3): 1274-8
[38] Kimura S, Kasuya Y, Sawamura T, et al. Conversion of big endothelin-1 to 21-residue endothelin-1 is essential for expression of full vasoconstrictor activity: structure-activity relationships of big endothelin-1. J Cardiovasc Pharmacol, 1989, 13(Suppl 5): S5-7
[39] Sawamura T, Kimura S, Shinmi O, Characterization of endothelin converting enzyme activities in soluble fraction of bovine cultured endothelial cells. Biochem Biophys Res Commun, 1990, 169(3): 1138-44
[40] Wu-Wong JR, Budzik GP, Devine EM, et al. Characterization of endothelin converting enzyme in rat lung. Biochem Biophys Res Commun, 1990, 171(3): 1291-6
[41] Schweizer A, Valdenaire O, Nelbock P, et al. Human endothelin-converting enzyme (ECE-1): three isoforms with distinct subcellular localizations. Biochem J, 1997, 328 (Pt 3): 871-7
[42] Valdenaire O, Lepailleur-Enouf D. A fourth isoform of endothelin-converting enzyme (ECE-1) is generated from an additional promoter molecular cloning and characterization. Eur J Biochem, 1999, 264(2): 341-9
[43] Muller L, Barret A, Etienne E, et al. Heterodimerization of Endothelin-converting Enzyme-1 Isoforms Regulates the Subcellular Distribution of This Metalloprotease. J Biol Chem, 2003, 278(1): 545-55
[44] Lüscher TF, Barton M. Endothelins and endothelin receptor antagonists: therapeutic considerations for a novel class of cardiovascular drugs. Circulation, 2000, 102(19): 2434-40.
[45] Ehrenreich H, Anderson RW, Fox CH, et al. Endothelins, peptides with potent vasoactive properties, are produced by human macrophages. J Exp Med, 1990, 172(6): 1741-8
[46] Kobayashi Y, Sakamoto Y, Shibasaki M,Human alveolar macrophages synthesize endothelins by thrombin. J Immunol, 1997, 158(11): 5442-7
[47] Nishida M, Springhom JP, Kelly RA, et al. Cell-cell signaling between adult rat ventricular myocytes and cardiac microvascular endothelial cells in heterotypic primary culture. J Clin Invest,
1993, 91(5): 1934-41
[48] De Keulenaer GW, Andries LJ, Sys SU. Endothelin-mediated positive inotropic effect induced by reactive oxygen species in isolated cardiac muscle. Circ Res, 1995, 76(5): 878-84
[49] Hemsen A, Lundberg JM. Presence of endothelin-1 and endothelin-3 in peripheral tissues and central nervous system of the pig. Regul Pept, 1991, 36(1): 71-83
[50] Dean R, Zhuo J, Alcorn D, et al. Cellular distribution of 125I-endothelin-1 binding in rat kidney following in vivo labeling. Am J Physiol, 1994, 267(5 Pt 2): F845-52
[51] Masaki T. Possible role of endothelin in endothelial regulation of vascular tone. Annu Rev Pharmacol Toxicol, 1995, 35:235-55
[52] Hislop AA, Zhao YD, Springall DR, et al. Postnatal changes in endothelin-1 binding in porcine pulmonary vessels and airways. Am J Respir Cell Mol Biol, 1995, 12(5): 557-66
[53] Chakravarthy U, Douglas AJ, Bailie JR, et al. Immunoreactive endothelin distribution in ocular tissues. Invest Ophthalmol Vis Sci, 1994, 35(5): 2448-5
[54] Casasco A, Benazzo M, Casasco M, et al. Occurrence, distribution and possible role of the regulatory peptide endothelin in the nasal mucosa. Cell Tissue Res, 1993, 274(2): 24l-7
[55] Svane D, Larsson B, Alm P, et al. Endothelin-1: immunocytochemistry, localization of binding sites, and contractile effects in human uteroplacental smooth muscle. Am J Obstet Gynecol, 1993, 168(1 Pt l): 233-41
[56] Davenport AP, Nunez DJ, Brown MJ. Binding sites for 125I-labelled endothelin-1 in the kidneys: differential distribution in rat, pig and man demonstrated by using quantitative autoradiography. Clin Sci (Lond), 1989, 77(2): 129-31
[57] Yoshimi H, Hirata Y, Fukuda Y, Regional distribution of immunoreactive endothelin in rats. Peptides, 1989, 10(4): 805-8
[58] Kloog Y, Ambar I, Sokolovsky M, et al. Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain. Science, 1988, 242(4876): 268-70
[59] Pemow J, Hemsen A, Lundberg JM. Tissue specific distribution, clearance and vascular effects of endothelin in the pig. Biochem Biophys Res Commun, 1989, 161 (2): 647-53
[60] Sirvio ML, Metsarinne K, Saijonmaa O, et al. Tissue distribution and half-life of 125I-endothelin in the rat: importance of pulmonary clearance. Biochem Biophys Res Commun, 1990, 167(3): 1191-5
[61] Shiba R, Yanagisawa M, Miyauchi T, et al. Elimination of intravenously injected endothelin-1 from the circulation of the rat. J Cardiovasc Pharmacol, 1989, 13(Suppl 5): S98-101
[62] Anggard E, Galton S, Rae G, et al. The fate of radioiodinated endothelin-1 and endothelin-3 in the rat. J Cardiovasc Pharmacoi, 1989, 13 (Suppl 5): S46-9
[63] Fukuroda T, Fujikawa T, Ozaki S, et al. Clearance of circulating endothelin-1 by ETB receptors in rats. Biochem Biophys Res Commun, 1994, 199(3): 1461-5
[64] Burkhardt M, Barton M, Shaw SG. Receptor- and non-receptor-mediated clearance of big-endothelin and endothelin-1: differential effects of acute and chronic ETA receptor blockade.
J Hypertens, 2000, 18(3): 273-9
[65] Bolger GT, Liard F, Krogsrud R, et al. Tissue specificity of endothelin binding sites. J Cardiovasc Pharmacol, 1990, 16(3): 367-75
[66] Sirvio ML, Saijonmaa O, Metsarinne K, et al. Degradation of endothelin-1 by extracts of rat lung, kidney, and liven Regul Pept, 1995, 55(3): 219-25
[67] Dupuis J, Goresky CA, Foumier A.Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors. J Appl Physiol, 1996, 81 (4): 1510-5
[68] Reinhart GA, Preusser LC, Burke SE, et al. Hypertension induced by blockade of ET_B receptors in conscious nonhuman primates: role of ETA receptors. Am J Physiol Heart Circ Physiol, 2002, 283(4): H1555-H1561.
[69] Koseki C, Imai M, Hiram Y, et al. Autoradiographic distribution in rat tissues of binding sites for endothelin: a neuropeptide? Am J Physiol, 1989, 256(4 Pt 2): R858-66
[70] Power RF, Wharton J, Zhao Y, et al. Autoradiographic localization ofendothelin-1 binding sites in the cardiovascular and respiratory systems.J Cardiovasc Pharmacol, 1989, 13(Suppl 5): S50-6
[71] Arai H, Hod S, Aramori I, et al. Cloning and expression of a cDNA encoding an endothelin receptor. Nature, 1990, 348(6303): 730-2
[72] Ferro CJ, Webb DJ. The clinical potential of endothelin receptor antagonists in cardiovascular medicine. Drugs, 1996,51(1):12-27
[73] Douglas SA, Meek TD, Ohlstein EH. Novel receptor antagonists welcome a new era in endothelin biology. Trends Pharmacol Sci, 1994, 15(9): 313-6
[74] Kame S, Jayawickreme CK, Lerner MR. Cloning and characterization of an endothelin-3 specific receptor (ETC receptor) from Xenopus laevis dermal melanophores. J Biol Chem, 1993, 268(25): 19126-33
[75] Karet FE, Kuc RE, Davenport AP. Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ETA and ETB in human kidney. Kidney Int, 1993, 44(1): 3642
[76] Molenaar P, O'Reilly G, Sharkey A, et al. Characterization and localization of endothelin receptor subtypes in the human atrioventricular conducting system and myocardium. Circ Res, 1993, 72(3): 526-38
[77] Warner TD, Mitchell JA, de Nucci G, et al. Endothelin-1 and endothelin-3 release EDRF from isolated perfused arterial vessels of the rat and rabbit. J Cardiovasc Pharmacol, 1989, 13 (Suppl 5): S85-8
[78] Hirata Y, Emori T, Eguchi S, et al. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J Clin Invest, 1993,91(4): 1367-73
[79] Davenport AP, O'Reilly G, Kuc RE. Endothelin ETA and ETB mRNA and receptors expressed by smooth muscle in the human vasculature: majority of the ETA sub-type. Br J Pharmacol, 1995, 114(6): 1110-6
[80] Clozel M, Gray GA, Breu V, et al. The endothelin ETB receptor mediates both vasodilation and vasoconstriction in vivo. Biochem Biophys Res Commun, 1992, 186(2): 867-73
[81] Teerlink JR, Breu V, Sprecher U, et al. Potent vasoconstriction mediated by endothelin ETB receptors in canine coronary arteries. Circ Res, 1994, 74(1): 105-14
[82] Seo B, Oemar BS, Siebenmann R, et al. Both ETA and ETB receptors mediate contraction to endothelin-1 in human blood vessels. Circulation, 1994, 89(3): 1203-8
[83] Cramer H, Muller-Esterl W, Schroeder C. Subtype-specific endothelin-A and endothelin-B receptor desensitization correlates with differential receptor phosphorylation. J Cardiovasc Pharmacol, 1998, 31(Suppl 1): S203-6
[84] Sanchez R, MacKenzie A, Farhat N, et al. Endothelin B receptor-mediated regulation of endothelin-1 content and release in cultured porcine aorta endothelial cell. J Cardiovasc Pharmacoi, 2002, 39(5): 652-9
[85] Imai T, Hiram Y, Emori T, et al. Induction ofendothelin-1 gene by angiotensin and vasopressin in endothelial cells. Hypertension, 1992, 19(9): 753-757
[86] Lee ME, Bloch KD, Clifford JA, et al. Quertermous T Functional analysis of the endothelin-1 gene promoter. Evidence for an endothelial cell-specific cis-acting sequence.J Biol Chem, 1990, 265(18): 10446-50
[87] Komuro I, Kurihara H, Sugiyama T, et al. Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett, 1988,238(2):249-52
[88] 申景玲，傅松滨，张贵寅．内皮素基因的研究进展．国外医学遗传学分册，2001，24(3)：120
[89] Shichiri M, Adachi S, Sedivy JM, et al. Biphasic Regulation of the Preproendothelin-1 Gene.by c-myc. Endocrinology, 1997, 138(11): 4584-4590
[90] 齐法莲．内皮素及其受体研究与心血管疾病．放射免疫学杂志，2002，15(4)：246-248
[91] Masatsugu K, Itoh H, Chun TH, et al. Shear stress attenuates endothelin and endothelin-converting enzyme expression through oxidative stress. Regul Pept, 2003, 111(1-3):13-9
[92] Wang DL, Wung BS, Peng YC, et al. Mechanical strain increases endothelin-1 gene expression via protein kinase C pathway in human endothelial cells. J Cell Physiol, 1995, 163(2): 400-6
[93] Yakubu MA, Leffler CW. Regulation of ET-1 biosynthesis in cerebral microvascular endothelial cells by vasoactive agents and PKC. Am J Physiol, 1999, 276 (2 Pt 1): C300-5
[94] Uhlmann D, Uhlmann S, Spiegel HU. Endothelin/nitric oxide balance influences hepatic ischemia-reperfusion injury. J Cardiovasc Pharmacol, 2000, 36(5 Suppi 1): S212-4
[95] Tabuchi Y, Nakamaru M, Rakugi H, et al. Effects of endothelin on neuroeffector junction in mesenteric arteries of hypertensive rats. Hypertension, 1990, 15(6 Pt 2): 739-43
[96] Horio T, Kohno M, Yokokawa K, Effect of hypoxia on plasma immunoreactive endothelin-1 concentration in anesthetized rats. Metabolism, 1991, 40(10): 999-1001
[97] Masaki T, Yanagisawa M, Inoue A, et al. Study on the endothelin gene and its expression. Jpn Circ J, 1990, 54(9): 1221-5
[98] Boulanger C, Luscher TF. Release of endothelin from the porcine aorta. Inhibition by endothelium-derived nitric oxide. J Clin Invest, 1990, 85(2): 587-90
[99] Lepailleur-Enouf D, Valdenaire O, Philippe M, et al. Thrombin induces endothelin expression in arterial smooth muscle cells. Am J Physiol Heart Circ Physiol, 2000, 278(5): H1606-12
[100] 韩正康．家畜生理学(第三版)．中国农业出版社，北京，1996：13
[101] Yoshizumi M, Kurihara H, Morita T, et al. Interleukin 1 increases the production ofendothelin-1 by cultured endothelial cells. Biochem Biophys Res Commun, 1990, 166(1): 324-9
[102] Kurihara H, Yoshizumi M, Sugiyama T, et al. Transforming growth factor-beta stimulates the expression of endothelin mRNA by vascular endothelial cells. Biochem Biophys Res Commun, 1989, 159(3): 1435-40
[103] Aramori I, Nakanishi S. Coupling of two endothelin receptor subtypes to differing signal transduction in transfected Chinese ham ster ovary cells. J Biol Chem, 1992, 267(18): 1246-8
[104] Haynes WG, Waugh CJ, Duckrell MC, et al. Modulators of calcium channels: their effects on endothelin-1 binding to cardiac membranes. J Cardiovasc Pharmacol, 1993, 22(suppl): S 154
[105] Inui T, Ninomiya H, Sasaki Y, et al. Selective activation of excitation-contraction coupling pathways by ETA and ETB receptors in guinea-pig tracheal smooth muscle. British Journal of Pharmacology, 1999, 126(4): 893-902
[106] Gong QY, Yang ZC, Cai H, et al. Effects of endothelin on porcine coronary arterial strips. Zhongguo Yao Li Xue Bao, 1989,10(6): 511-5
[107] Endoh M, Fujita S, Yang HT, et al. Endothelin: receptor subtypes, signal transduction, regulation of Ca~(2+) transients and contractility in rabbit ventricular myocardium. Life Sci, 1998, 62(17-18): 1485-9
[108] Woo SH, Lee CO. Effects ofendothelin-1 on Ca~(2+) signaling in guinea-pig ventricular myocytes: role of protein kinase C. J Mol Cell Cardiol, 1999, 31(3): 631-43
[109] Takenaka T, Epstein M, Forster H, Attenuation of endothelin effects by a chloride channel inhibitor, indanyloxyacetic acid. Am J Physiol, 1992, 262(5 Pt 2): F799-806
[110] Spatz M, Kawai N, Bembry J, et al. Human brain capillary endothelium: modulation of K+ effiux and K+, Ca~(2+) uptake by endothelin. Neurochem Res, 1998, 23(8): 1125-32
[111] Fujitani Y, Ueda H, Okada T, et al. A selective agonist of endothelin type B receptor, IRL 1620, stimulates cyclic GMP increase via nitric oxide formation in rat aorta. J Pharmacol Exp Ther, 1993, 267(2): 683-9
[112] Resink TJ. Inducible endothelin mRNA expression and peptide secretion in cultured human vascular smooth muscle cells. Biochem Biophys REs Commun, 1990, 168:1303～1310
[113] Saito S, Hirata Y, Imai T, et al. Autocrine regulation of the endothelin-1 gene in rat endothelial cells. J Cardiovasc Pharmacol, 1995, 26(Suppl 3): S84-7
[114] Oriji GK, Keiser HR. Protein Kinase C mediates angiotensin 11-induced contractions and the release of Endothelin and prostacyclin in rat aortic rings. Prostaglandins Leukotrienes Essential Fatty Acids, 1997, 57(2): 135
[115] Sharma AC, Motev. SJ, farias S. Sepsis alters myocardial and plasma concentrations of endotheline and nitric oxide in rats. J Mol Cell Cardiol, 1997, 29:1469
[116] Pittet JF, Morel DR, Hemsen A. Elevated plasma endothelin-1 concentrations areas sociated with the severity of illness in patients with sepsis. Ann Surg, 1991, 213:261
[117] Sakurai T, Morimoto H, Kasuya Y, et al. Level of ETB receptor mRNA is down-regulated by endothelins through decreasing the intracellular stability of mRNA molecules. Biochem Biophys Res Commun, 1992, 186(1): 342-7
[118] Roubert P, Gillard V, Plas P, et al. Down-regulation of endothelin binding sites in rat vascular smooth muscle cells. Am J Hypertens, 1990, 3(4): 310-2
[119] Miasiro N, Paiva AC. Homologous desensitization of the effects of endothelin on rabbit aorta rings and on cultured rat aorta smooth muscle cells. Eur J Pharmacol, 1990, 179(1-2): 151-8
[120] Nayler WG, Ou RC, Gu XH, et al. Effect of amlodipine pretreatment on ischaemia-reperfusion-induced increase in cardiac endothelin-1 binding site density. J Cardiovasc Pharmacol, 1992, 20(3): 416-20
[121] Clozel M. Down-regulation of endothelin receptor by autocrine production of endothelin-1. Am J Physiol. 1993, 265(4): C188～C192
[122] de Nucci G, Thomas R, D'Orleans-Juste P, et al. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyelin and endothelium-derived relaxing factor. Proc Natl Acad Sci, U S A 1988,85(24):9797-800
[123] Hinojosa-Laborde C, Lange DL. Endothelin regulation of adrenal function. Clin Exp Pharmacol Physiol, 1999, 26(12): 995-9
[124] Minkes RK, MacMillan LA, Bellan JA, et al. Analysis of regional responses to endothelin in hindquarters vascular bed of cats. Am J Physiol, 1989, 256(2 Pt 2): H598-602
[125] Minkes RK, Higuera TR, Rogers GF, et al. Cardiovascular responses to vasoactive intestinal contractor, a novel endothelin-like peptide. Am J Physiol, 1990, 259(4 Pt 2): H1152-60
[126] Piacentini L, Gray M, Honbo NY, et al. Endothelin-1 stimulates cardiac fibroblast proliferation through activation of protein kinase C. J Mol Cell Cardiol, 2000, 32(4): 565-76
[127] Rosen B, Barg J, Zimlichman R. The effects of angiotensin Ⅱ, endothelin-1, and protein kinase C inhibitor on DNA synthesis and intracellular calcium mobilization in vascular smooth muscle cells from young normotensive and spontaneously hypertensive rats. Am J Hypertens, 1999, 12(12 Pt 1-2): 1243-51
[128] Hafizi S, Allen SP, Goodwin AT, et al. Endothelin-1 stimulates proliferation of human coronary smooth muscle cells via the ET(A) receptor and is co-mitogenic with growth factors. Atherosclerosis, 1999, 146(2): 351-9
[129] Iwasaki H, Eguchi S, Marumo F, et al. Endothelin-1 stimulates DNA synthesis of vascular smooth-muscle cells through transactivation of epidermal growth factor receptor. J Cardiovasc Pharmacol, 1998, 31 (Suppl 1): S182-4
[130] Ouchi Y, Kim S, Souza AC, et al. Central effect of endothelin on blood pressure in conscious rats. Am J Physiol, 1989, 256(6 Pt 2): H1747-51
[131] Shichiri M, Hirata Y, Kanno K, et al. Effect of endothelin-1 on release of arginine-vasopressin
from perifused rat hypothalamus. Biochem Biophys Res Commun, 1989, 163(3): 1332-7
[132] Zhang M, Olsson Y. Reactions of astrocytes and microglial cells around hematogenous metastases of the human brain. Expression of endothelin-like immunoreactivity in reactive astrocytes and activation ofmicroglial cells. J Neurol Sci, 1995, 134(1-2): 26-32
[133] Takagi M, Tsukada H, Matsuoka H, Inhibitory effect of endothelin on renin release in vitro. Am J Physiol, 1989, 257(6 Pt 1): E833-8
[134] Munter K, Hackenthal E. The effects ofendothelin on renovascular resistance and renin release. J Hypertens Suppl, 1989, 7(6): S276-7
[135] Matsumura Y, Nakase K, Ikegawa R, et al. The endothelium-derived vasoconstrictor peptide endothelin inhibits renin release in vitro. Life Sci, 1989, 44(2): 149-57
[136] Cozza EN, Gomez-Sanchez CE, Foecking MF, et al. Endothelin binding to cultured calf adrenal zona glomerulosa cells and stimulation of aldosterone secretion. J Clin Invest, 1989, 84(3): 1032-5
[137] Gellai M, DeWolf R, Pullen M, et al. Distribution and functional role of renal ET receptor subtypes in normotensive and hypertensive rats. Kidney Int, 1994, 46(5): 1287-94
[138] Polak K, Luksch A, Frank B, Regulation of human retinal blood flow by endothelin-1. Exp Eye Res, 2003, 76(5): 633-640
[139] Kawamura H, Oku H, Li Q, et al. Endothelin-induced changes in the physiology of retinal pericytes. Invest Ophthalmol Vis Sci, 2002, 43(3): 882-8
[140] Dashwood MR, Timm M, Kaski JC. Regional variations in ETA/ETB binding sites in human coronary vasculature. J Cardiovasc Pharmacol, 1995, 26(Suppl 3): S351-4
[141] Yamazaki T, Komuro I, Kudoh S, et al. Endothelin-1 is involved in mechanical stress-induced cardiomyocyte hypertrophy. J Biol Chem, 1996, 271(6): 3221-8
[142] Sakai S, Miyauchi T, Sakurai T, et al. Endogenous endothelin-1 participates in the maintenance of cardiac function in rats with congestive heart failure. Marked increase in endothelin-1 production in the failing heart. Circulation, 1996, 93(6): 1214-22
[143] Bobik A, Grooms A, Millar JA, Growth factor activity of endothelin on vascular smooth muscle. Am J Physiol, 1990, 258(3 Pt 1): C408-15
[144] Timm M, Kaski JC, Dashwood MR. Endothelin-like immunoreactivity in atherosclerotic human coronary arteries. J Cardiovasc Pharmacol, 1995, 26(Suppl 3): S442-4
[145] Kobayashi T, Miyauchi T, Sakai S, et al. Expression of endothelin-1, ETA and ETB receptors, and ECE and distribution of endothelin-1 in failing rat heart. Am J Physiol, 1999, 276(4 Pt 2): H1197-206
[146] Li H, Chen SJ, Chen YF, et al. Enhanced endothelin-1 and endothelin receptor gene expression in chronic hypoxia. J Appl Physiol, 1994, 77(3): 1451-9
[147] Kitsukawa Y, Gu ZF, Hildebrand P, et al. Gastric smooth muscle cells possess two classes of endothelin receptors but only one alters contraction. Am J Physioi, 1994, 266(4 Pt 1): G713-21
[148] Lazaratos S, Kashimura H, Nakahara A, et al, Gastric ulcer induced by submucosal injection of
ET-1: role of potent vasoconstriction and intraluminal acid. Am J Physiol, 1993, 265(3 Pt 1): G491-8
[149] Masuda E, Kawano S, Michida T, et al. Plasma and gastric mucosal endothelin-1 concentrations in patients with peptic ulcer. Dig Dis Sci, 1997, 42(2): 314-8
[150] Khan MA, Dashwood MR, Mumtaz FH, et al. Upregulation of endothelin A receptor sites in the rabbit diabetic kidney: potential relevance to the early pathogenesis of diabetic nephropathy. Nephron, 1999, 83(3): 261-7
[151] Dashwood MR, Timm M, Muddle JR, et al. Regional variations in endothelin-1 and its receptor subtypes in human coronary vasculature: pathophysiologicai implications in coronary disease. Endothelium, 1998, 6(1): 61-70
[152] Xu SW, Denton CP, Dashwood MR, et al. Endothelin-1 regulation of intercellular adhesion molecule-1 expression in normal and sclerodermal fibroblasts. J Cardiovasc Pharmacoi, 1998, 31(Suppl 1): S545-7
[153] Watanabe T, Suzuki N, Shimamoto N, et al. Contribution of endogenous endothelin to the extension of myocardial infarct size in rats. Circ Res, 1991, 69(2):370-7
[154] Watanabe T, Suzuki N, Shimamoto N, et al. Endothelin in myocardial infarction. Nature 1990, 344(62): 114
[155] Saijonmaa O, Ristimaki A, Fyhrquist F. Atrial natriuretic peptide, nitroglycerine, and nitroprusside reduce basal and stimulated endothelin production from cultured endothelial cells. Biochem Biophys Res Commun, 1990, 173(2): 514-20
[156] Urakami A, Todo S, Zhu Y, et al. Attenuation of ischemic liver injury by monoclonal anti-endothelin antibody, AwETN40. J Am Coll Surg, 1997, 185(4): 358-64
[157] Deng LY, Schiffrin EL. Effect of antihypertensive treatment on response to endothelin of resistance arteries of hypertensive rats. J Cardiovasc Pharmacol, 1993,21(5):725-31
[158] McMahon EG, Palomo MA, Brown MA, et at. Effect of phosphoramidon (endothelin converting enzyme inhibitor) and BQ-123 (endothelin receptor subtype A antagonist) on blood pressure in hypertensive rats. Am J Hypertens, 1993, 6(8): 667-73
[159] Matsuura A, Okumura H, Ashizawa N, et al. Big endothelin-1-induced sudden death is inhibited by phosphoramidon in mice. Life Sci, 1992, 50(21): 1631-8
[160] Matsumura Y, Ikegawa R, Suzuki Y, Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: the relationship to endothelin-1 levels in the cerebrospinai fluid. Life Sci, 1991, 49(11): 841-8
[161] Ihara M, Noguchi K, Saeki T, et al. ioiogical profiles of highly potent novel endothelin antagonists selective for the ETA receptor. Life Sci, 1992; 50(4): 247-55
[162] 张建伟．内皮素拮抗剂研究进展．国外医学生理、病理科学与临床分册，1997，17(4)：349-350
[163] Stewart DJ, Levy RD, Cemacek P, et al. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease? Ann Intern Med, 1991, 114(6): 464-9 ; ::
[164] Dupuis J, Stewart DJ, Cernacek P, et al. Human pulmonary circulation is an important site for both clearance and production of endothelin-1. Circulation, 1996, 94(7): 1578-84
[165] Kohno M, Yasunari K, Murakawa K, et al. Plasma immunoreactive endothelin in essential hypertension. Am J Med, 1990, 88(6): 614-8
[166] 冉丕鑫，徐军，陈顺存，等．慢性缺氧对大鼠肺动脉和右心室内皮素与一氧化氮合成酶mRNA表达的影响．中华医学杂志，1995，75(8)：479
[167] 冉丕鑫，徐军，陈顺存，等．慢性缺氧影响肺脏内皮素和一氧化氮成酶mRNA的表达[J]．中国病理生理杂志，1997，13(1)：35
[168] 冉丕鑫，杜志强，陈颜芳，等．内皮素对离体肺动脉及肺动脉平滑肌细胞的作用．中国动脉硬化杂志，2000，8(2)：151-153
[169] Filep JG. Endothelin peptides: biological actions and pathophysiological significance in the lung. Life Sci, 1993; 52(2): 119-33
[170] Homma S, Maclean MR, McCulloch KM, etal. Endotheline ETA-and ETB-receptor mediated vasoconstriction in rat pulmonary arteries and arterioles. J Cardiovasc pharmacol, 1994, 23: 838
[171] Viossat I, Chapelat M, Chabrier PE, Validation of radioimmunoassay of tissue and plasma endothelin-1. Arch Mal Coeur Vaiss, 1990, 83(8): 1263-5
[172] Cassin S, Kristova V, Davis T, et al. Tone-dependent responses to endothelin in the isolated perfused fetal sheep pulmonary circulation in situ. J Appl Physiol, 1991, 70(3): 1228-34
[173] Nakamichi K, Ihara M, Kobayashi M, et al. Different distribution of endothelin receptor subtypes in pulmonary tissues revealed by the novel selective ligands BQ-123 and [Alal,3,11,15]ET-1. Biochem Biophys Res Commun, 1992, 182(1): 144-50
[174] Goldie RG, D'Aprile AC, Self GJ, et al. The distribution and density of receptor subtypes for endothelin-1 in peripheral lung of the rat, guinea-pig and pig. Br J Pharmacol, 1996, 117(4): 729-35
[175] Ryan US.Receptors on pulmonary endothelial cells. Am Rev Respir Dis, 1990,141(3 Pt 2):S 132-6
[176] MacLean MR, McCulloch KM, Baird M. Endothelin ETA- and ETB-receptor-mediated vasoconstriction in rat pulmonary arteries and arterioles. J Cardiovasc Pharmacol, 1994, 23(5): 838-45
[177] Takahashi H, Soma S, Muramatsu M, et al. Discrepant distribution of big endothelin (ET)-1 and ET receptors in the pulmonary artery. Eur Respir J, 2001, 18(1): 5-14
[178] Takahashi H, Soma S, Muramatsu M, et al. Upregulation of ET-1 and its receptors and remodeling in small pulmonary veins under hypoxic conditions. Am J Physiol Lung Cell Mol Physiol, 2001,280(6): L1104-14
[179] Sudjarwo SA, Hori M, Takai M, et at. A novel subtype of endothelin B receptor mediating contraction in swine pulmonary vein. Life Sci, 1993, 53(5): 431-7
[180] 王玉玮．内皮素代谢及其与肺血管病变的关系．医学综述，1995，1(10)：447-449
[181] Guarda E, Katwa LC, Myers PR, et al. Effects of endothelins on collagen tumover in cardiac fibroblasts. Cardiovasc Res, 1993, 27(12): 2130-4
[182] Mallat A, Fouassier L, Preaux AM, et al. Growth inhibitory properties of endothelin-1 in human hepatic myofibroblastic Ito cells. An endothelin B receptor-mediated pathway. J Clin Invest, 1995, 96(1): 42-9
[183] Murlas CG, Gulati A, Singh G, et al. Endothelin-1 stimulates proliferation of normal airway epithelial cells. Biochem Biophys Res Commun, 1995, 212(3): 953-9
[184] Takimoto M, Oda K, Sasaki Y, et al. Endothelin-A receptor-mediated prostanoid secretion via autocrine and deoxyribonucleic acid synthesis via paracrine signaling in human bronchial epithelial cells. Endocrinology. 1996, 137(11): 4542-50
[185] Filep JG, Battistini B, Sirois P. Induction by endothelin-1 of epithelium-dependent relaxation of guinea-pig trachea in Vitro: role for nitric oxide. Br J Pharmacol, 1993, 109(3): 637-44
[186] Michael JR, Markewitz BA. Endothelins and the lung. Am J Respir Crit Care Med, 1996, 154(3 Pt 1): 555-81
[187] Markewitz BA, Kohan DE, Michael JR. Endothelin-1 synthesis, receptors, and signal transduction in alveolar epithelium: evidence for an autocrine role, Am J Physiol, 1995, 268(2 Pt 1): L192-200
[188] Tamaoki J, Kanemura T, Sakai N, et al. Endothelin stimulates ciliary beat frequency and chloride secretion in canine cultured tracheal epithelium. Am J Respir Cell Mol Biol, 1991, 4(5): 426-31
[189] Horgan MJ, Pinheiro JM, Malik AB. Mechanism of endothelin-1-induced pulmonary vasoconstriction. Circ Res, 1991, 69(1): 157-64
[190] Ishikawa T, Yanagisawa M, Kimura S, et al. Positive chronotropic effects of endothelin, a novel endothelium-derived vasoconstrictor peptide. Pflugers Arch, 1988, 413(1): 108-10
[191] Maguire JJ, Davenport AP. ETA receptor-mediated constrictor responses to endothelin peptides in human blood vessels in vitro. Br J Pharmacol, 1995,115(1):191-7.
[192] Toga H, Ibe BO, Raj JU. In vitro responses of ovine intrapuimonary arteries and veins to endothelin-1. Am J Physiol, 1992, 263(1 Pt 1): L15-21
[193] Zellers TM, McCormick J, Wu Y. Interaction among ET-1, endothelium-derived nitric oxide, and prostacyclin in pulmonary arteries and veins. Am J Physiol, 1994,267(1 Pt 2): H139-47
[194] 郭光伟．内皮素与心肺血管系统．山西临床医药杂志，1997，6(1)：1-3
[195] Hasleton PS, Heath D, Brewer DB. Hypertensive pulmonary vascular disease in states of chronic hypoxia. J Pathol Bacteriol, 1968, 95(2): 431-40.
[196] Heath D, Segel N, Bishop J. Pulmonary veno-occlusive disease. Circulation, 1966, 34(2): 242-8
[197] Rabinovitch M, Bothwell T, Hayakawa BN, et al. Pulmonary artery endothelial abnormalities in patients with congenital heart defects and pulmonary hypertension. A correlation of light with scanning electron microscopy and transmission electron microscopy. Lab Invest, 1986, 55(6): 632-53
[198] Hung KS, McKenzie JC, Mattioli L, et al. Scanning electron microscopy of pulmonary vascular endothelium in rats with hypoxia-induced hypertension. Acta Anat (Basel), 1986,126(1):13-20
[199] 林春龙，张珍祥，徐永健，等．慢性阻塞性肺病患者内皮素-1 水平与肺血流动力学的关系．中国现代医学杂志，1998，8(1)：17-21
[200] 石云，杜军保，汤秀英，等．慢性缺氧性肺动脉高压大鼠肺血管显微结构研究 实用儿科临床杂志，2002，17(1)：1-4
[201] Dzau VJ, Gibbons GH. Endothelium and growth factors in vascular remodeling of hypertension. Hypertension, 1991, 18(5 Suppl): Ⅲ115-21
[202] Barer GR, Cai YN, Russell PC, et al. Reactivity and site of vasomotion in pulmonary vessels of chronically hypoxic rats: relation to structural changes. Am Rev Respir Dis, 1989, 140(5): 1483-5
[203] 陈光喜，王小龙，黄克和．肉鸡腹水综合征的临床病理学研究．中国兽医杂志，1996，22(12)：10-11
[204] 高洪．高原地区肉鸡腹水症病理形态学观察．中国兽医科技，1996，26(11)：35-36
[205] 何诚，贾君镇，高娃，等．肉鸡腹水症发病机理研究：低温处理后肉鸡肺脏超微结构的病理学变化．电子显微学报，2002，21(2)：192-195
[206] 王世英，张登荣，张登岭，等．肉鸡腹水症心肝肺显微和超微结构研究．中国兽医学报，1997，17(3)：292-293
[207] Yoshibayashi M, Nishioka K, Nakao K, et al. Plasma endothelin concentrations in patients with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation. Circulation, 1991, 84(6): 2280-5
[208] Chen W, Cheng D. Effects of endothelin receptor antagonist on the hypoxic pulmonary hypertension. Hua Xi Yi Ke Da Xue Xue Bao, 2000, 31(3): 370-2, 386
[209] Yang X, Chen W, Li F. The change and distribution of endothelin-1 in lung of hypoxic pulmonary hypertension rat. Hua Xi Yi Ke Da Xue Xue Bao, 2000,31(1):30-3
[210] 王秋月，李尔然，赵桂喜．老年肺心病患者血浆内皮素-1与肺血流动力学的关系．中国老年学杂志，1998，18：55-56
[211] Stelzner TJ, O'Brien RF, Yanagisawa M, et al. Increased lung endothelin-1 production in rats with idiopathic pulmonary hypertension. Am J Physiol, 1992, 262(5 Pt 1): L614-20
[212] Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med, 1993,328(24): 1732-9
[213] Allen SW, Chatfield BA, Koppenhafer SA, et al. Circulating immunoreactive endothelin-1 in children with pulmonary hypertension. Association with acute hypoxic pulmonary vasoreactivity. Am Rev Respir Dis, 1993,148(2): 519-22
[214] Kourembanas S, Marsden PA, McQuillan LP, et al. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J Clin Invest, 1991, 88(3): 1054-7
[215] Elton TS, Oparil S, Taylor GR. Normobaric hypoxia stimulates endothelin-1 gene expression in the rat. Am J Physiol, 1992, 263(6 Pt 2): R1260-4
[216] Li H, Elton TS, Chen YF, et al. Increased endothelin receptor gene expression in hypoxic rat lung. Am J Physiol 1994, 266(5 Pt 1): L553-60
[217] 刘绪万．内皮素与肺动脉高压．国外医学儿科学分册，1995，22(6)：289-292
[218] Goresky CA, Foumier A. Pulmonary clearance of circulating endothelin-1 in dogs in vivo: exclusive role of ETB receptors. J Appl Physiol, 1996, 81 (4): 1510-5
[219] Wort SJ, Woods M, Warner TD, et al. Endogenously Released Endothelin-1 from Human Pulmonary Artery Smooth Muscle Promotes Cellular Proliferation. Am. J. Respir. Cell Mol. Biol, 2001, 25(1): 104-110
[220] Chen SJ, Chen YF, Opgenorth TJ, et al. The orally active nonpeptide endothelin A-receptor antagonist A-127722 prevents and reverses hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling in Sprague-Dawley rats. J Cardiovasc Pharmacol, 1997, 29(6): 713-25
[221] Givertz MM, Colucci WS, LeJemtel TH, et al. Acute endothelin A receptor blockade causes selective pulmonary vasodilation in patients with chronic heart failure. Circulation, 2000, 101(25): 2922-7
[222] Coe Y, Haleen SJ, Welch KM, et al. The endothelin-A-receptor antagonist PD 180988 (CI-1034) selectively reverses the pulmonary vasoconstrictor response to hypoxia in the lamb. J Cardiovasc Pharmacol, 2000, 36(5 Suppl 1): S331-3
[223] Franco-Cereceda A, Holm P. Selective or nonselective endothelin antagonists in porcine hypoxic pulmonary hypertension? J Cardiovasc Pharmacol, 1998, 31(Suppl 1): S447-52
[224] Montagnani M, Vulpis V, Nazzaro P, et al. Endothelin-1-receptor-mediated responses in resistance vessels of young and adult spontaneously hypertensive rats. J Hypertens, 2000,18(7): 893-900
[225] 郝春荣，熊密，王迪浔，等．低氧诱导因子-1α和内皮素-1基因在大鼠低氧性肺动脉高压中的表达．中华病理学杂志，2002，31(2)：140-142
[226] Zamora MA, Dempsey EC, Walchak SJ, et al. BQ123, an ETA receptor antagonist, inhibits endothelin-1-mediated proliferation of human pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol, 1993, 9(4): 429-33
[227] Soma S, Takahashi H, Muramatsu M, et al. Localization and distribution of endothelin receptor subtypes in pulmonary vasculature of normal and hypoxia-exposed rats. Am J Respir Cell Mol Biol, 1999, 20(4): 620-30
[228] Li H, Elton TS, Chen YF, et al. Increased endothelin receptor gene expression in hypoxic rat lung. Am J Physiol, 1994, 266(5 Pt 1): L553-60
[229] Davie N, Haleen SJ, Upton P, et al. ET_A and ET_B Receptors Modulate the Proliferation of Human Pulmonary Artery Smooth Muscle Cells. Am. J. Respir. Crit. Care Med., 2002, 165(3): 398-405
[230] Ivy DD, Yanagisawa M, Gariepy CE, et al. Exaggerated hypoxic pulmonary hypertension in endothelin B receptor-deficient rats. Am J Physiol Lung Cell Mol Physiol, 2002,282(4):L703-t2
[231] 贾建锋，杜军保，齐建光．大内皮素-1的生物转化对兔肺动脉收缩反应的影响．中华医学杂志，1999，79(8)：632-634
[232] Hasunuma K, Rodman DM, O'Brien RF, et al. Endothelin 1 causes pulmonary vasodilation in rats. Am J Physiol, 1990, 259(1 Pt 2): H48-54
[233] Nagase T, Fukuchi Y, Matsui H, et al. In vivo effects of endothelin A-and B-receptor antagonists in guinea pigs. Am J Physiol, 1995, 268(5 Pt 1): L846-50
[234] Pons F, Loquet I, Touvay C, et al. Comparison of the bronchopulmonary and pressor activities of endothelin isoforms ET-1, ET-2, and ET-3 and characterization of their binding sites in guinea pig lung. Am Rev Respir Dis, 1991, 143(2): 294-300
[235] Noguchi S, Kashihara Y, Bertrand C. The induction of a biphasic bronchospasm by the ETB agonist, IRL 1620, due to thromboxane A2 generation and endothelin-1 release in guinea-pigs. Br J Pharmacol, 1996, 118(6): 1397-402
[236] Katoh H, Terada H, Iimuro M, et al. Heterogeneity and underlying mechanism for inotropic action ofendothelin-1 in rat ventricular myocytes. Br J Pharmacol, 1998, 123(7): 1343-50
[237] Zamora MR, Stelzner TJ, Webb S, et al. Overexpression ofendothelin-1 and enhanced growth of pulmonary artery smooth muscle cells from fawn-hooded rats. Am J Physiol, 1996, 270(1 Pt 1): L101-9
[238] Hahn AW, Regenass S, Resink TJ, et al. Morphogenic effects of endothelin-1 on vascular smooth muscle cells. J Vase Res, 1993,30(4): 192-201
[239] Mansoor AM, Honda M, Saida K, et al. Endothelin induced collagen remodeling in experimental pulmonary hypertension. Biochem Biophys Res Commun, 1995, 215(3): 981-6
[240] Dawes KE, Peacock AJ, Gray AJ, et al. Characterization of fibroblast mitogens and chemoattractants produced by endothelial cells exposedto hypoxia. Am J Respir Cell Mol Biol, 1994, 10(5): 552-9
[241] Filep JG, Battistini B, Sirois P. Pharmacological modulation of endothelin-induced contraction of guinea-pig isolated airways and thromboxane release. Br J Pharmacol, 1991, 103(3): 1633-40
[242] Kovacs EJ, DiPietro LA. Fibrogenic cytokines and connective tissue production. FASEB J, 1994, 8(11): 854-61
[243] Battistini B, Chailler P, D'Orleans-Juste P, et al. Growth regulatory properties of endothelins. Peptides, 1993, 14(2): 385-99
[244] 乔健，董世山，乔惠理，等．右心导管法直接测定肉仔鸡肺动脉压．中国农业大学学报，1998，3(3)：117-118
[245] 杨小东，陈文彬，陈俊杰．内皮素在低氧性肺动脉高压大鼠肺内表达和水平变化的研究．中华内科杂志，1996，35(11)：734-737
[246] Zoccali C, Leonardis D, Parkongo S, et al. Urinary and plasma endothelin-1 in essential hypertension and in hypertension secondary to renoparenchyma disease. Nephrol Dial Transplant, 1995, 10(8): 1320
[247] 唐轶，崔志澄．内皮素与血管内皮舒张因子的相互调节和作用关系．北京医学，1998，20(1)：35-37
[248] Iscon TC, Vaclav H, Kenneth E, et al. Increased endotheliun-derived NO in hypertensive pulmonary circulation of chronically hypoxic Rats. J Appl Physiol, 1994, 76(2): 933
[249] 汤健，唐朝枢，杨军，等．内皮素．北京医科大学、中国协和医科大学联合出版社，1994，163-164，224
[250] Salvati P, Chierchia S, DhoL, etal. Proarrhythmic activity of intra-coronary endothelin in dogs; sedation to the site of administration and to changes inregional flow. J Cardiovasc Pharmacol, 1991, 17(6): 1007-1014
[251] 汤健，杨青，张继峰．环五肽BQ123对内皮素-1的拮抗效应．北京医科大学学报，1992，24(6)：431-434
[252] Leite-Moreira AF, Bras-Silva C, Pedrosa CA, et al. ET-1 increases distensibility of acutely loaded myocardium: a novel ETA and Na~+/H~+ exchanger-mediated effect. Am J Physiol Heart Circ, 2003, 284(4): H1332-9
[253] Goraca A. Negative chronotropic effect of endothelin-1 (ET-1) in the cardiac pacemaker tissue. J Physiol Pharmacol, 2003, 54(1): 53-63
[254] 姚平，潘敬远，詹澄扬．内皮素对成年离体心室肌细胞内游离浓度的影响及机制．中国病理生理杂志，1995，15(4)：18-22
[255] 程德云，陈文彬，肖欣荣．Cromakalim阻断内皮素-1介导肺动脉高压的研究．华西医科大学学报，1998，29(1)：79-81
[256] Rizzoni D, Porteri E, Piccoli A, et al. The vasoconstriction induced by endothelin-1 is mediated only by ET(A) receptors in mesenteric small resistance arteries of spontaneously hypertensive rats and Wistar Kyoto rats. J Hypertens, 1997, 15(12 Pt 2): 1653-7
[257] Danthuluri NR, Brock TA. Endothelin receptor-coupling mechanisms in vascular smooth muscle: a role for protein kinase C. J Pharmacol Exp Ther, 1990, 254(2): 393-9
[258] Hubel CA, Highsmith RF. Endothelin-induced changes in intracellular pH and Ca2+ in coronary smooth muscle: role of Na(+)-H+ exchange. Biochem J, 1995, 310 (Pt 3): 1013-20
[259] Saito Y, Nakao K, Itoh H, et al. Endothelin in human plasma and culture medium of aortic endothelial cells detection and characterization with radioimmunoassay using monoclonal antibody. Biochem Biophys Res Commun, 1989, 161(1): 320-6
[260] Koshi T, Torii T, Ami K, et al. Inhibition of endothelin (ET)-1-and ET-2-induced vasoconstriction by anti-ET-1 monoclonal antibody. Chem Pharm Bull (Tokyo), 1991, 39(5): 1295-7
[261] White DG, Cannon TR, Garratt H, et al. Endothelin ETA and ETB receptors mediate vascular smooth-muscle contraction. J Cardiovasc Pharmacol, 1993, 22 (Suppl8): S 144～148.
[262] Schuize-Neick I, Li J, Reader JA, et al. The endothelin antagonist BQ123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease. J Thorac Cardiovasc Surg, 2002, 124(3): 435-41.
[263] Bonvallet S. T, Oka M, Yano M, et al. BQ123, an ETA receptor antagonist, attenuates endothelin-1-induced vasoconstriction in rat pulmonary circulation. J Cardiovasc Pharmacol, 1993, 22(1): 39-43.
[264] Münter K, Ehmke H, Kirchengast M. Maintenance of blood pressure in normotensive dogs by endothelin. Am J Physiol Heart Cire Physiol, 1999, 276(3): H1022-H1027
[265] Reinhart GA, Preusser LC, Opgenorth TJ, et al. Endothelin and ETA receptors in long-term arterial pressure homeostasis in conscious nonhuman primates. Am J Physiol Regul Integr Comp Physiol, 2000, 279(5): R1701-R1706
[266] Warner TD, Allcock GH, Vane JR. Reversal of established responses to endothelin-1 in vivo and in vitro by the endothelin receptor antagonists, BQ-123 and PD 145065. Br J Pharmacol, 1994, 112(1): 207-13
[267] Owe-Young R, Schyvens CG, Qasabian RA, et al. Transcriptional down-regulation of the rabbit pulmonary artery endothelin B receptor during phenotypic modulation. Br J Pharmacol, 1999, 126(1): 103-10
[268] Ito H, Hiroe M, Hirata Y, Fujisaki H, et al. Endothelin ETA receptor antagonist blocks cardiac hypertrophy provoked by hemodynamic overload. Circulation, 1994, 89(5): 2198-203
[269] Kawai N, Yamamoto T, Yamamoto H, et al. Functional characterization of endothelin receptors on cultured brain capillary endothelial cells of the rat. Neurochem, 1997, 31(4): 597-605
[270] 王金勇，王小龙，向瑞萍，等．环境低温和T_3对肉鸡内皮素、一氧化氮和肺动脉压的影响．中国兽医学报，2002，22(5)：509-511
[271] 何诚．肉鸡腹水症发病机理研究：低温环境对肉鸡心功能、肺动脉高压的影响及其机制探讨：[博士学位论文]．北京：2001：47
[272] Criscione L, Thomann H, Luu TD. Sensitivity and reactivity to endothelin-1 in mesenteric beds and aortic rings of 4-week-old spontaneously hypertensive rats. Clin Exp Hypertens, 1992, 14(3): 453-67
[273] Tomobe Y, Ishikawa T, Yanagisawa M, et al. Mechanisms of altered sensitivity to endothelin-1 between aortic smooth muscles of spontaneously hypertensive and Wistar-Kyoto rats. J Pharmacol Exp Ther, 1991, 257(2):555-61
[274] Clozel M. Endothelin sensitivity and receptor binding in the aorta of spontaneously hypertensive rats. Hypertens, 1989, 7(11): 913-7
[275] Touyz RM, Deng LY, Li JS, et al. Differential effects of vasopressin and endothelin-1 on vascular contractile and calcium responses in pressurized small arteries from spontaneously hypertensive rats. J Hypertens, 1996, 14(8):983-91
[276] Roberts-Thomson P, McRitchie RJ, Chalmers JP. Experimental hypertension produces diverse changes in the regional vascular responses to endothelin-1 in the rabbit and the rat. J Hypertens, 1994, 12(11): 1225-34
[277] Oparil S, Chen SJ, Meng QC, Elton TS, et al. Endothelin-A receptor antagonist prevents acute hypoxia-induced pulmonary hypertension in the rat. Am J Physiol, 1995, 268(1 Pt 1): L95-100
[278] Balyakina EV, Chen D, Lawrence ML, et al. ET-1 receptor gene expression and distribution in L1 and L2 cells from hypertensive sheep pulmonary artery. Am J Physiol Lung Cell Mol Physiol, 2002, 283(1): L42-51
[279] wideman R F Jr, Ismail M,Kirby Y K, et al. Furosemide reduces the incidence of pulmonary hypertension syndrome (ascites) in broilers exposed to cool environmental temperatures. Poult Sci, 1995, 74(2): 314-322
[280] 董世山，乔健，栗少文，等．肺动脉高压与肉鸡腹水综合征发生发展的关系．畜牧兽医学报，2000，31(4)：325-330
[281] MacLean, MR. Endothelin-1: a mediator of pulmonary hypertension? Pulm Pharmacol Ther, 1998, 11(2): 125-132
[282] Janakidevi, K, Fisher MA, Del Vecchio PJ, et al. Endothelin-1 stimulates DNA synthesis and proliferation of pulmonary artery smooth muscle cells. Am J Physiol Cell Physiol, 1992, 263: C1295-C1301
[283] Matsuura A, Yamochi W, Hirata K, et al. Stimulatory interaction between vascular endothelial growth factor and endothelin-1 on each gene expression. Hypertension, 1998, 32(1):89-95
[284] Peifley KA, Winkles JA. Angiotensin Ⅱ and endothelin-1 increase fibroblast growth factor-2 mRNA expression in vascular smooth muscle cells. Biochem Biophys Res Commun, 1998, 242(1): 202-8
[285] 张丽萍，范英群，曾强，等．卡托普利及抗内皮素抗体对自发性高血压大鼠血压的急性作用．解放军医学杂志，1996，21(3)：205-6
[286] 林江凯，王宪荣．内皮素在神经源性肺水肿中的意义．中华实验外科杂志，1996，13(6)：365-6