摘要
肉鸡肺动脉高压综合征(pulmonary hypertension syndrome,PHS)亦称肉鸡腹水综合征(ascites syndrome,AS),又称“心衰综合征”(heart failure syndrome,HFS)等,是快速生长肉鸡的一种常见非传染性疾病,以明显的腹水和心、肺功能衰竭为特征。全世界养鸡业每年因此病而损失巨大,随着养鸡业的发展,该病的发生有逐渐上升之势。肺动脉压升高是肉鸡肺动脉高压综合征的重要特点并对它的形成起决定性作用。内皮素(endothelin-1,ET-1)是一种由内皮细胞合成和分泌的、具有强烈收缩血管作用和促进细胞增生的血管活性多肽,心钠素(atrial natriuretic peptide,ANP)、血管紧张素Ⅱ(angiotensin Ⅱ,AⅡ)、NO等在心血管系统功能的调节中也起着重要作用。为研究肉鸡PHS的发病机理,本试验主要从ET-1角度出发,从以下几个方面对本试验进行了研究:用高能日粮饲喂较多肉鸡的方法获得PHS肉鸡模型;用放射免疫分析方法比较了不同腹水程度肉鸡在不同日龄时血浆和主要组织中ET-1的含量,同时还用硝酸还原酶法和放射免疫法对NO、NOS、ANP、AⅡ在肉鸡PHS发病过程中的作用加以研究;通过免疫组织化学染色方法和RT-PCR的方法研究了ETA受体及其基因在不同腹水程度和不同日龄肉鸡体内的分布情况及其表达水平;通过短期静脉注射ET-1、内皮素受体拮抗剂BQ123和长期给予ET-1的方法研究了ET-1、BQ123对肉鸡肺动脉压、PHS发病率、主要组织病理变化以及一些生理生化指标的影响;同时利用细胞培养的方法研究了ET-1、BQ123、L-Arg、L-NAME对培养的肉鸡心肌细胞的作用,从而比较全面地从ET-1的角度研究了肉鸡PHS的发病机理。主要试验结果如下:
(1) 用高能日粮饲养肉鸡时从10日龄起有PHS发生,发病率为5.3%-6.7%,与自然情况下的发病率基本相同;右心导管法研究发现2-6周龄时肺动脉高压(PH)组肉鸡的平均肺动脉压(mPAP)极显著(p<0.01)高于正常组肉鸡;腹水心脏指数(ascites heart index,AHI)也极显著(p<0.01)或显著(p<0.05)高于正常组,且随日龄的增长有上升的趋势;PH组肉鸡血浆和主要组织(心、肝、肺、肾)中ET-1在2-5周龄时也显著(p<0.01)或极显著(p<0.05)高于正常组,而在6周龄时则呈现出复杂的变化;血浆ANP、NO、AⅡ在2-5周龄时显著或极显著高于正常组,随日龄的增长有升高的趋势,而在6周龄时则呈现出不规则的变化;几种组织相比,肺脏ET-1的含量最高;mPAP与血浆ET-1相关性显著,与血浆NO没有相关性,血浆ET-1与NO也没有明显的相关性。
(2) 用免疫组织化学染色的方法和RT-PCR的方法对不同腹水程度、不同日龄肉鸡ETAR及其基因在体内定位及其表达变化的情况进行了探讨。免疫组织化学染色
Pulmonary hypertension syndrome (PHS) of broilers is also called ascites syndrome in broiler or heart failure syndrome (HFS) in broiler. The term "ascites" actually refers to the fluid accumulated in the abdominal cavity as a consequence of heart failure. A frequent occurrence of ascites has been a difficult problem detrimental to the poultry industry around the world. Approximately 4% of all broilers die from pulmonary hypertension syndrome, causing a loss estimated at $1 billion annually. General agreement exists regarding the reasonable etiology of ascites irresoluble. Now most of the investigators focused on pulmonary hypertension because they thought it was the center link of this disease. Endothelin-1 (ET-1) is a potent vasoconstrictive peptide that was isolated initially from the conditioned medium of cultured endothelial cells. It is a pathogenic mediator with a number of deleterious effects, including vasoconstriction, fibrosis, vascular hypertrophy, and inflammation. Atrial natriuretic peptide, angiotensin Ⅱ and nitric oxide also takes an important role in cardiovascular system. In order to illuminate the etiopathogenesis of pulmonary hypertension syndrome in broiler from the point of endothelin-1, natural pulmonary hypertension syndrome broiler cases were got through using hyperalimentation dietary to feed a great deal of commercial broiler chickens. Radioimmunoassay was used to detect endothelin-1(ET-1), ANP and AⅡ in plasma, heart, liver, lung and kidney of different degree ascites broilers and normal broilers at different weeks of age. The AHI and mPAP of 3 to 6 weeks were measured as well. At the same time, nitrate reductase method was used to detect the level of nitric oxide (NO) and nitric oxide synthase (NOS) in plasma of different degree ascites broilers at the age of 3,4,5 and 6 weeks. Imunohistochemistry and reverse transcriptase polymerase chain reaction (RT-PCR) method were used to illustrate the distribution and changes of ETA receptor in different degree of ascites in broiler. In order to study the effect of ET-1 and BQ123 on the mean pulmonary arterial pressure (mPAP), morbidity of PHS, pathological change of the main tissues, physiological index and biochemical indicator, different dose of ET-1 and BQ123 were i.v. injected into the broiler. Myocardial cells of broiler were also cultured to illustrate the effection of different doses of ET-1, BQ123, L-Arg and L-NAME on the cultured myocardial cells.(1) Natural pulmonary hypertension syndrome broiler cases were appear from the age of 10 days after hyperalimentation dietary were used to feed a great deal of commercial Arbor Acre broiler chickens, the morbility is about 5.3% or 6.7%. Right heart catheter
was used to determine the mean pulmonary arterial pressure, it was found that, compared with the normal group, the AHI and mPAP of PH group were higher or significantly higher, the tendency of increment with the days delaying was observed. From 3 weeks of age, the level of plasma and tissue ET-1 of the PH group was higher or significantly higher than that of the normal group. At 6 weeks of age, the level of ET-1 in plasma, lung, kidney of PH group decreased slightly, though it was still higher than that of the normal group. The level of ET-l of tissues was higher than that of plasma, and the level of lung ET-1 was higher than that of other organs. The level of NO and NOS of the two groups increased with the days delayed, and the PH group was significantly higher than the normal group. Besides, there was a significant positive correlation between mPAP and ET-1, but no significant correlation was found between mPAP and plasma NO of the two groups. It is concluded that ET-1 and NO took part in the formation and development of pulmonary hypertension syndrome in broilers and played an important role in it.(2) Immunohistochemical method and reverse transcriptase polymerase chain reaction (RT-PCR) method were used to study the distribution and expression of ETA receptor (ETAR) in different degree of ascites broilers. It was found that the ETAR expressed extensively in the main tissues of the broilers. In heart, it mainly expressed in cardiac muscle cell envelope, cardiac pericardium and vascular smooth muscle. In liver, it mainly distributed in hepatic cell envelope and Kupffer's cells. In lung, it mainly expressed in blood vessel, bronchus secundarius, parabronchus and pulmonary alveoli. In distal convoluted tubule, renal glomeruli, macula densa, medullary loop and vessel of kidney of kidney, it was also has different degree of expression. Compared with the normal group, the expression of ETAR in lung blood vessel and pulmonary alveoli of PH group, light ascites group and heavy ascites group is higher or significant higher. But with the development of the degree of ascites, the expression of ETAR was decreased, and the expression of ETAR in the PH group is the highest. With the development of the degree of ascetes, the expression of ETAR of the heart was decreased or significant decreased, but it was still higher than the normal group. The expression of ETAR of myocardium of right ventricle was significant higher than of myocardium of left ventricle. In liver, the expression of ETAR in liver cells was higher than that of the normal group and the heavy ascites group. Compared with the normal group, the expression of ETAR in hepatic blood vessel was obviously decreased. In kidney, the expression of ETAR in nephric tubule, glomeruli of kidney and macula densa also showed complicated changes with the development of the degree of ascites. The primers of broiler endothelin type A receptor
gene was used to RT-PCR. The heart cDNA was obtained from the normal group broiler of 16, 30 days old and heavy ascites broiler of 30 days old. The results showed that the expression of EDNRA mRNA of the normal 16days old broilers was obviously lower than that of the 30days old broilers. The expression of EDNRA mRNA of the heavy ascites broiler was obviously lower than that of the normal group of broilers.(3) When different degree of ascites group compared each other, the mean pulmonary arterial pressure, ascites heart index (AHI), right ventricle and body weight ratio (TV/BW), the level of plasma ET-1, plasma ANP and plasma NO were all significantly or every significantly increased with the development of ascites degree. Plasma and tissue endothelin-1 (ET-1), atrial natriuretic polypeptide (ANP), mPAP, AHI and NO of the normal, light and heavy ascites broiler groups were measure. It was found that AHI and mPAP of the light ascites group were higher or significantly higher than that of the normal group, and the heavy ascites group was higher or significantly higher than that of the light ascites group. The trend of increment with the days delaying was observed too. The change tendency of plasma and lung inducible nitric oxide synthase (iNOS), constitutive nitric oxide synthase (cNOS) level was complex. Compared with the normal and light ascites group, the level of plasma iNOS in heavy ascites group were higher or significantly higher. The trend of increment of iNOS with the day delaying was complex, it was decreased at first and then increased. The level of cNOS in heavy ascites was lower or significant lower than the normal and light ascites group. It showed complex change as broilers growing. Radioimmunoassay was used to detect tissue ET-1 and ANP of broilers in different degree ascites group of 5 weeks old broilers. It found that the content of ANP and ET-1 is significantly or very significantly increased with the development of the ascites. The level of the ET-1 and ANP in lung and heart is the highest than in other tissues, and the level of ANP in tissues was higher than that of plasma. Besides, there were significant positive correlation between mPAP and AHI, between plasma ANP, ET-1 and AHI, mPAP. There were significant positive correlation among plasma mPAP, AHI and cardiac ET-1 at 5 weeks of age, but no significant correlation was found between plasma NO and plasma ET-1, plasma ANP, cardiac ET-1.(4) Twenty eight days old broilers were randomly divided into several groups with 8 replicates each, infused intravenously with different dose of ET-1 and BQ123. The control group was injected 0.86% NaCl. The mean pulmonary arterial pressure (mPAP) was measured, and plasma A I , ANP, ET-1 at different time after the broilers were injected different dose of ET-1 and BQ123. The mPAP decreased from time 0 to 5 min and then
began to increase from time 5 to 30 min when the broilers were injected with ET-1 24, 120, 240ng/kg BW. The effective dose of ET-1 was 240ng/kg BW to make mPAP increase. BQ123 can decrease mPAP of the broilers with dose dependent and it also can counteract the increasing effect of blood pressure after injected ET-1, but it can't counteract the decreasing effect of blood pressure at the beginning of the injection. In other experiment, 170 broilers were divided into 3 groups: a control group (group C, 50 broilers), group A and B (60 broilers each) that intravenously injected with 240ng/kg BW and 360ng/kg BW ET-1, respectively. The PHS morbidity of group A was higher than that of group C but lower than group B. The right/total ventricular weight ratio (RV/TV) and mPAP were higher in group A and B than in group C. There was the same tendency of the values of packed cell volume (PCV) and plasma nitric oxide (NO) when compared group A, B with group C. The tissue slice of broilers showed that pathology changes appeared in the main tissues after ET-1 was injected into the broiler with long-term.(5) Enzyme digestion was used to cultivate myocardial cell of broilers. In this experiment, methyl thiazolyl tetrazolium (MTT) and 3H-TdR, 3H-Pro, 3H-Leu were used to study the effect of ET-1 and BQ123 on the broiler myocardial cell. In the present study, it indicated that when the concentration of ET-1 exceeded 10"8mol/L, ET-1 was obviously promoted the growth and hypertrophy of the myocardial cells. If the ET-1 concentration was higher, the growth promotion effect on the myocardial cells was better. When the concentration of BQ123 exceeded 10"8mol/L, it can completely counteract the promotion effect of ET-1 on myocardial cells of broilers, and the inhibitory action was obvious if the concentration of BQ123 was higher. Fluorescent labeling was used to study the effect of ET-1, BQ123, L-Arg and L-NAME on the change of [Ca2+]i in myocardial cells. ET-1 could promote [Ca2+]i of myocardial cells inflowing and BQ123 could counteract this effect soundly, but BQ123 could not counteract the transient increase effect of ET-1.
引文
1.方芳,张放,刘景生.胞浆内信息传递及第二信使.见:刘景生主编.细胞信息与调控.北京:北京医科大学、中国协和医科大学联合出版社,1998,183-190
2.王世英,张登荣,张登岭.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
3.王红宁.禽呼吸系统疾病.北京:中国农业出版社,2002,318-325
4.王良兴.低氧高二氧化碳对肺动脉内皮素-1基因表达的影响.中华结核和呼吸杂志,2000,10:591-594
5.王金勇,王小龙,向瑞平.L-精氨酸对肉鸡肺动脉压和腹水综合征发生的影响.南京农业大学学报,2001,24(2):98-101
6.王金勇,王小龙,向瑞平.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
7.王金勇,王小龙,向端平.日粮中添加L-NAME对肉鸡腹水综合征的影响及其机理研究.中国兽医学报,2001,21(6):45-47
8.王庭槐,吴滨,朱小南,潘敬运.内皮素对培养心肌细胞内游离钙浓度的作用.生理学报,1999,51(4):391-396
9.王树林.肉鸡腹水综合征及其防治.辽宁畜牧兽医,2001,(6):16-20
10.冯晓东,蔡英年.ET-1和NO对肺动脉平滑肌细胞DNA合成的作用及缺氧对其调制的研究.中国医学科学院学报,1995,17(3):172-176
11.石岩,何诚,梁礼成。肉鸡腹水症发病机理研究:Ⅳ低温处理对肉鸡心肌肌浆网钙泵活性与Ca~_(2+)摄取的影响.中国农业大学学报
12.石岩,何诚,梁礼成.血管紧张素Ⅱ及内皮素在肉鸡肺动脉高压发病中的作用.中国实验动物学报,2003,11(3):173-176
13.任玉红,崔英英.肉鸡腹水综合症的临床及病理形态学观察.山西农业大学学报,1997,17(3):283-285
14.刘健华,梁礼成,金久善.正常鸡、亚临床腹水鸡和腹水鸡肺外动脉舒张反应性的比较.畜牧兽医学报,2003,34(3):262-267
15.刘健华,梁礼成,金久善.肺组织中的NOS在肉鸡腹水症发生发展中的变化.畜牧兽医学报,2002,33(5):458-462
16.刘健华.肉鸡腹水症肺动脉高压形成机理的研究.[博士学位论文].北京:中国农业大学,2001
17.华泽钊.低温生物学研究的物理化学基础.低温生物学.长沙:湖南科学技术出版社,1997,41-71
18.吉小莉,王峰,温守明.精氨酸及RGD肪类体外血管活性作用评价.现代应用药学,1995,12(5):10-11
19.孙卫东,王小龙,张克春.高钠所致肉鸡肺动脉高压模型的心电图学研究.南京农业大学学报,1998,53(3):23-25
20.汤芹.腹水症的发症机理.国外畜牧科技,1998,4
21.汤健,唐朝枢,杨军.内皮素.北京:北京医科大学中国协和医科大学联合出版社, 1994.163-164,224
22.汤键,唐朝枢.循环系统的内分泌功能.北京医科大学中国协和医科大学联合出版社,1989(第1版),93-10
23.祁国奇.心钠素与肺动脉高压.国外医学呼吸系统分册.1994,14(4):183-184
24.纪求尚,王树春,朱式娟.肺动脉高压对心衰病人血浆内皮素水平的影响.山东医药,1995,2:15-16
25.齐永华,王文魁.肉鸡腹水综合征研究进展.动物医学进展,2003,24(3):54-57
26.齐法莲,徐军,杨道理.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):246-249
27.何诚,赵德明,梁礼成.低温高能日粮对肉鸡肺动脉和腹水症的影响.畜牧兽医学报,2000,31(1):35-41
28.何诚,贾君镇,高娃.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
29.何诚,梁礼成,赵德明.肉鸡肺动脉高压综合征发病机理研究:Ⅰ肉鸡和蛋仔鸡左右心室功能的比较研究.畜牧兽医学报,2002,33(6):573-575
30.何诚,梁礼成,赵德明.血栓素和前列环素在肉鸡肺动脉压中的作用.动物医学进展,2001,22(4):110-112
31.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:中国农业大学,2001
32.吴秀萍,田旻,李艳敏.血浆心钠素(ANF)含量与心脏功能相关性的研究.伤残医学杂志,2003,11(3):45-46
33.张宁仔,杜日映.心血管病学-理论与实践.北京:人民军医出版社,1999,33-38
34.张克春,王桂军,王小龙等.饮水高钠诱发的肉鸡腹水综合征的血液流变学特征.中国兽医学报,1998,6:592-595
35.张均田,李锡明,石成璋.用Fura-2/AM测定细胞内游离钙浓度的方法.中国药学杂志,1991,26(11):655-658
36.张洪友,王德利,孙洪军.肉鸡腹水症血液生理生化指标的研究.黑龙江八一农垦大学学报,1999,11(2):62-6
37.李炘.内皮素与肺动脉高压.国外医学心血管分册,1996,23(5):266-268
38.李国红,梁延杰,陆江明,王晓红,杨毅,许海月.大鼠缺氧性肺动脉高压时内皮素和一氧化氮的变化.解放军医学杂志,2001,26(10):752-754
39.李建鑫,崔秀江,何英.肉仔鸡腹水症发生的原因及防治.饲料世界,2002,1:27-28
40.李家奎,郭定宗,吴建光.肺动脉高压肉鸡和腹水肉鸡血清、肝、肺等组织NO含量及某些酶活性的变化.华中农业大学学报,2000,19(5):478-480
41.李晓瑜.日粮酸碱平衡也许与猝死综合征和腹水症有关.国外畜牧科技,1996,23(4):32-35
42.李锦春,王小龙,孙卫东.肉鸡肺动脉高压综合征自然病例肺细小动脉病理改变的图像分析.中国兽医学报,1999,5:479-482
43.李锦春,王小龙,孙卫东.高钠所致肺动脉高压肉鸡毛细小动脉病理改变的图像分析.畜牧兽医学报,2000,31(5):441-447
44.李锦春,王小龙,肉鸡肺动脉高压综合征研究进展.中国兽医杂志,1998.2:44-46
45.杨军,唐朝枢.内皮素的基因表达和释放调节.国外医学内分泌分册,1992,12(2):65
46.杨军.影响离体灌流大鼠主动脉释放内皮素的因素探讨.心肺血管学报,1992,11(2):35-36
47.杨青,张继峰,赵云海.内皮素A受体拮抗剂BQ123降压作用的研究.中国病理生理杂志,1993,9(6):678-681
48.杨钢,席正雄,万渝.应激对大鼠脑血管、心血管、肾上腺血管紧张素含量的变化.生理学报,1993,45(5):505-509
49.杨雷,袁涛.高血压病患者肿瘤坏死因子-α、一氧化氮与内皮素的变化及意义.华中医学杂志,2001,25(1):51
50.杨鹰,乔健,孙茂红,张建军,董世山,武振龙.内皮素-1对蛋鸡股动脉压和肺动脉压的影响.中国农业大学学报,2003,8(1):103-105
51.杨鹰,乔健,陈越.内皮素在肉鸡腹水综合征肺动脉高压中的病理学意义.中国兽医学报,2003,23(6):626-627
52.杨鹰,乔健,武振龙,陈越.内皮素受体拮抗剂BQ123对蛋用鸡肺血流动力学的影响.中国兽医科技,2003,3(5):9-13
53.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
54.杨新良,闫丽娟.肺部内皮素的生理病理学意义.国外医学生理、病理科学与临床分册,1998,3:203-206
55.杨新良,周文波.内皮素在肺部的作用及其研究进展.国外医学呼吸系统分册,1998,2:104-111
56.汪德生,孙磊,任维,等.尾部悬吊大鼠胸主动脉和肺动脉舒张反应性的动态变化.中华航空航天学杂志,2001,12(3):145-149
57.苏玉英.高海拔地区肉鸡腹水症后血液的变化.中国家禽,1996,7:3
58.苏静怡.心血管疾病的病理生理基础和发病机制.北京医科大学、协和医科大学联合出版社,1994,140-150
59.陈建康,邹万忠,由江峰.用半定量RT-PCR检测内皮素及其受体mRNA在不同组织中的表达.肾脏病与透析肾移植杂志,1995,6(4):512-515
60.陈屏,袁文俊.内皮素A受体拮抗剂BQ123抗内皮素的心律失常.铁道医学,1995,23(5):267-268
61.陈鸿军,韩博.环境低温及L-精氨酸对肉鸡腹水综合征的影响.中国家禽,2001,23(18):8-10.
62.高原,孙红梅,宋彩琴.L-精氨酸(L-Arg)和NaHCO_3降低肉鸡综合征病死率的田间试验.中国家禽,2002,24(20):10-12
63.陈霞,黄丽英,曾强.缺氧性肺动脉高压大鼠内皮素的变化.中华医学杂志,1993,7:400-401
64.周谦,李茂琼,蒋明瑞.急性左心功能衰竭患者血浆ET、ANF及血清EDF含量变化.放射免疫学杂志,1998,11(4):235-237
65.周东海,郭定宗,杨世锦.内皮素对肺动脉高压综合征肉鸡的影响.中国农业科学,2004,37(6):912-916
66.周洪,张晨晖,李倩红.内皮素对血管平滑肌细胞中一氧化氮合成酶基因表达的影响.中 国高血压杂志.1994,2(2):75-77
67.治军.肉鸡腹水综合征研究进展.畜牧与兽医,1999,31(1):39-40
68.苒丕鑫,钟南山.生长因子、原癌基因与低氧性肺动脉高压.基础医学与临床.1996,16(1):1-4
69.郑从义.细胞培养物的低温冻存.低温生物学.长沙:湖南科学技术出版社,1997,171-188
70.金咸蓉.花生四烯酸与低氧性肺动脉高压.基础医学与临床,1996,16(1):26-60
71.姚平,潘敬运,詹澄扬,周丽丽.不同浓度ET-1引起心肌细胞[Ca~(2+)]i升高作用的量效关系.暨南大学学报(医学版),1999,20(2):42-46
72.赵刚,张雪平,李冬娜,高捍杰,陈瑞华,贾弘.鸡发育过程肌组织核提抽物结合活性与AChRC亚基基因持续表达的关系.中国生物化学与分子生物学报,2000,16(5):669-673
73.赵慧颖,下川宏明.一氧化氮合酶抑制剂(L-NAME)的药理作用与慢性血管效应.药学学报,1999,34(9):646-651
74.赵慧颖,赵利华,郭新雯.N-硝基L-精氨酸甲酯对大鼠动脉内皮功能及结构的影响.中国循环杂志 1998,13(4):245-247
75.郝唯蔚,杨晔,俞启福.中度急性缺氧对血浆内皮素含量的影响.航天医学与医学工程,1994,7(3):190～191
76.钟小宁,梁国容,何志义.血管内皮生长因子和内皮素在低氧性肺血管重建中的作用.中华内科杂志,2001,40(8):525-529
77.钟启胜,赵铁军.原发性肺动脉高压的研究进展.心血管病学进展,1999,20(4):197-200
78.钟慈声,孙安阳.一氧化氮的生物医学.上海:上海医科大学出版社,1997.6-9
79.唐轶.ET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
80.黄岚,祝善俊,孟素荣.L-精氨酸和NG-甲基-L-精氨酸对血管内皮细胞释放EDRF的影响.第三军医大学学报,1996,18(2):140-142
81.程显升.肺血管疾病学.北京医科大学、中国协和医科大学联合出版社,1993,67-75
82.程德云,陈文彬.内皮素受体拮抗剂预防低氧性肺高压的实验研究.中华内科杂志,1999,38(9):631-632
83.程德云,陈文斌.一氧化氮对肺动脉高压的作用研究进展.中华结核和呼吸杂志,1994,17(3):141-143
84.董世山,乔健,乔惠理.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):325-326
85.董世山,乔健,赵立.鸡肺动脉平滑肌细胞培养及免疫组化鉴定.中国农业大学学报,2002,7(3):99-102
86.董世山,乔健,赵立.鸡心肌细胞培养及免疫组化鉴定.中国兽医杂志,2003,39(2):14-15
87.董世山,乔健,栗绍文.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
88.韩博,王小龙.腹水综合征肉鸡环核苷酸与血管内皮衍生因子动态变化及添加L-精氨酸的预防机理.中国农业科学,2003,36(5):577-582
89.鲁凯伍,侯铁胜,傅强.内皮素受体拮抗剂PD142893对大鼠损伤脊髓血流及功能的影响.Acad J Sec Mil Med Univ,1999,20(8):519-521
90.戴爱国,张珍祥,牛汝楫.大鼠肺内NOS之分布及缺氧对其活性的影响.衡阳医学学院报, 1995, 23(3): 157-161
91. Abassi Z, Karram T, Ellaham S. Implications of the natriuretic peptide system in the pathogenesis of heart failure : diagnostic and therapeutic importance. Pharmacology Therapy. 2004, 102 (3) : 223-241
92. Agnoletti G, Panzali A. Activation of ANP synthesis during congestive heart failure in rats treated with monocrotaline. American Journal of Physiology, 1995, 268 : H391-H398
93. Akimoto K, Miyata A, Hayakawa K. Plasma and atrial levels of atrial natriuretic peptide (ANP) n pulmonary hypertensive rats. Life Science, 1988, 43 (14): 1 125
94. Andreis P G, Neri G, Tortorella C. Mechanisms transducing the aldosterone secretagogue signal of endothelins in the human adrenal cortex. Peptides, 2002, 23 : 561-566
95. Armstead W M. Influence of endothelin on piglet arterial microcirculation. Am J Physiol, 1989, 257 : 707
96. Artinez D A, Diaz G J Effect of graded levels of dietary nickel and manganese on blood haemoglobin content and pulmonary hypertension in broiler chickens. Avian Pathology, 1996, 25 (3) : 537-549
97. Artinez-lemus L A, Miller W N, Jehrey J S. Echocardiographic study of pulmonary hypertension syndrome in broiler chickens . Avian disease, 2000, 41 (1): 74-78
98. Assanzadeh M, Buyse J, Decuypere E. Relationship between myocardical P-adrenergic receptor characteristics and induce of ascites in broiler chickens. Avian Pathology, 2001, 30 (2) : 169-174
99. Balog J M, Anthony N B, Copper M A. Ascites syndrome and related Pathologies in feed restricted broilers raised in hypobaric chamber. Poultry Science, 2000, 79 (3): 318-323
100. Balog J M, Burton R, Smith H, et al. Effect of a urease inhibitor and ceiling fans on ascites in broilers, 2. Blood variables, ascites score and body and organ weights. Poultry Science, 1994, 73 : 810-816
101. Balog J M, Juff G R, Rath N C. Effect of dietary aspirin on ascites in broilers raised in a hypobaric chamber. Poult Sci, 2000, 79 (8) : 1101-1105
102. Battistini B, Botting R, Wanner T D. Endothelin: A knockout in Landon. Trends Pharmacol Sci, 1996, 16 (7): 217-221
103. Becuypere E, Bvyse J, Burs N. Ascites in broiler chickens: exogenous and endogenous structural and functional casual factors. World's Poultry Science Jounal, 2000, 56 (4) : 367-377
104. Benchekroun M T, Gros-Louis N, Ghassan B. R-type calcium channel involved in endothelin-1-induced contraction of rabbit aorta. J Cardiovasc Pharmacol, 1995, 26 (Suppl.3) : S300-S302
105. Bernard O A M, Jennerr J, Pym R A E. Evalution of serum troponin T, packed cell volume, hemoglobin and red cell count in the determination of susceptibility of broiler chickens to ascites. Philippine Journal of veterinary medicine, 2000, 37 : 31-37
106. Bertenshaw S R, Rogers R S, Stem M K. Phosphorus containing inhibitors of endothelin converting enzymes: effects of the electronic nature of phosphorus on the inhibitor potency. J Med Chem, 1993,36: 173
107. Besse S, Tangw y S, Rion B. Coronary and aorticvaso reactivity protection with endothelin receptor antagonist, bosentan, after ischemia and hypoxia in aged rats. Eur J Pharmacol, 2001, 432 : 167-175
108. Beziey. Interactions between endothelin-1 and atrial natriuretic peptide influence cultured chick cardiac myocyte contractility. Eur J Pharmacol, 1996,311 (2): 241-248
109. Bihovsky R, Levinson BL, Loewi RC. Hydroxamic acid as potent inhibitors of endothelin converting enzyme from human bronchiolar smooth muscle. J Med Chem, 1995,38 :119
110. Biswas N K, Bhowmik, M K, Dalapati, M R ascites syndrome ascites syndrome in broiler chickens : II analysis and interpretation of ascetic fluid. Indian Journal of Animal Research, 1995,296(1): 1-5
111. Bond J M, Julian R J, Sqires E J. Effect of dietary flax oil and hypobaric hypoxia on right vertricular hypertrophy and ascites in broiler chickens. British Poultry science, 1996, 37 (4) : 731-741
112. Bonvalle S T, Zamora M R, Hasunuma K. BQ123, an ETA-receptor antagonist, attenuates hypoxic pulmonary hypertension in rats. Am J Physiol, 1994, 266 : H1327-H1331
113. Bonvallet ST, Oka M, Yano M. BQ-123, an ETA receptor antagonist, attenuates endothelin-1-induced vasoconstriction in rat pulmonary circulation. J Cardiovasc Pharmacol, 1993,22(1):39-43
114. Braquet P, Touvay C, Lagente V, et al. Effect of endothelial-1 on blood pressure and bronchopulmonary system of the guinea pig. J Cardovasc Pharmacol, 1989, 13 (suppl 5) : S143-S1461
115. Brodde O E, Michel M C, Zerkowski H R. Signal transduction mechanisms controlling cardiac contractility and their alterations in chronic heart failure. Cardiovasc Res, 1995, 30 (4) : 570-584
116. Brooker G, Murad F, Cyclic J. Cyclic guanosine (3', 5')-monophosphate, cGMP. Nucleotide Res. 1980, 6 (6): 469-478
117. Cardillo C, Campia U, Bryant M B. Increased activity of endogenous endothelin in patients with type Ⅱ diabetes mellitus. Circulation, 2002, 106(14): 1783-1787
118. Cawthon. D, K. B. Eers, and W. G. Bottje. Electron transport chain defect and Inefficient respiration may both underlie pulmonary hypertension syndrome (Ascites) -associated mitochondria dysfunction in broilers. Poultry Sci. 2001, 80 : 474-484
119. Chakrbarfi A, Chandra S A, therapeutic approach to ascites syndrome in broiler chickens. Indian veterinary journal, 2001, 78 (1): 1056-1057
120. Champion, Hunter Clay, Bivalacqua. Role of arginase in bleomycin-induced pulmonary hypertension in the mouse: influence of gene transfer in vivo. FASEB Journal, 2003,17 (4) : 308
121. Dewile, Buys N, Albers G. The effect of acetylsalicylic acid and cold stress on the susceptibility of broilers to the ascites syndrome. British poultry science, 1996, 37(5): 1003-1013
122. Diaz G. J. and Julian R. J. Lesions in broiler chickens following experimental intoxication with cobalt. Avian Pathology, 1995,24 (1) : 109-120
123. Diaz-Craz, A., C. Nava, R. Villanueva, M. Serret, R. Guinzberg, and E. Pina. 1996. Hepatic and cardiac oxidative stress and other metabolic changes in broilers with the ascots syndrome. Poultry Sci. 15:900-903
124. Dinesman J L, Lowenstein C J, Snyder S H. Molecular mechanisms of nitric oxide regulation. Circulation Research, 1993, 73 (2): 217-222
125. Doust J A, Glasziou P P, Pietrzak E. A systematic review of the diagnostic accuracy of natriuretic peptides for heart failure. Archives of Internal Medicine, 2004, 164 (18) : 1978-1984
126. Duru F, Barton M, Thomas F. Endothelin and cardiac arrhythmias : doendothelin antagonists have a therapeutic potential as aniarrhythmic drugs Cardiovasc Res, 2001,49 : 272-280
127. Earle W R, Sanford K K, Evans V J. Influence of inoculum size on proliferation in tissue cultures. J Nat Cancer Inst. 1951, 12 : 133-153
128. Enedike H J. Role of endothelins and nitric oxide in hepatic reperfusion in jury in the rat. Hepatolohy, 1998,27 (3) : 755-764
129. Enkvetchadul B. Pulmonary arteriole hypertrophy in broiler with pulmonary hypertension syndrome. Poultry Science, 1995, 74 : 1 676-1 682
130. Fagan KA, Morrissey B, Fouty B W. Upregulation of nitric oxide synthase in mice with severe hypoxia-induced pulmonary hypertension. Respiratory Research, 2001,2 (5): 306-313
131. Fink CA, Moskal M, Firoozia F. Design and synthesis of potent thiol-based inhibitors of endothelin converting enzyme-1. Bioorg Med Chem Lett, 2000, 10(17): 2037-2039
132. Fontana F, Bernardi P, Tartuferi L. Mechanisms of hypertension in patients with chronic obstructive pulmonary disease and acute respiratory failure. Am J Med, 2000, 109 (8) : 621-627
133. Forman M F, Wideman R F. Renal responses of normal and preascitic broilers to systemic hypotension induced by unilateral pulmonary artery occlusion. Poultry Science, 1999, 78 (12) : 1 773-1 785
134. Forman M F, Widman R F. Measurements of pulmonary arterial pressure in anesthetized male broilers at two to seven weeks of age. Poultry Science, 2000, 79 (11): 1645-1649
135. Furukawa T, Ito H, Nitta J. Endothelin-1 enhances calcium entry through T-type calcium channels in cultured neonatal rat ventricular myocytes. Circ Res, 1992, 71 : 1242-1253
136. Geng A L, Guo Y M, Yang Y. Reduction of ascites mortality in broilers by coenzyme Q10. Poultry Science, 2004, 83 : 1587-1593
137. Giaid A, Saleh D. Reduced expression of endothelial nitric oxide synthase in the lungs of patients with pulmonary hypertension. The New England Journal of Medicine, 1995, 333 (4) : 214-221
138. Giannessi D, Del Ry S, Vitale R L. The role of endothelins and their receptors in heart failure. Pharmacol Res, 2001, 43 (2): 111-126
139. Gorenflo M, Bettendorf M, Ulmer H E. Oxygen-mediated pulmonary vasodilation and plasma levels of endothelin-1, atrial natriuretic peptides and cyclic GMP in patients with left-to-right shunt and pulmonary hypertension. Zeitschrift fur Kardiologie, 2000, 89 (2): 100-108
140. Grohe C, Nouskas J, Vetter H. Effects of nisoldipine on endothe lin-1 and angiotensin 11 -induced immediate/early gene expression and protein synt hesis in adultrat ventricular cardiomyocytes. J Cardiovasc Pharmacol. 1994, 24 (1): 13-16
141. Hasenfuss G, Just H. Myocardial phenotype changes in heart failure: cellular and subcellular adaptations and their functional significance. Br Heart J 1994;72 (supplement) : S10-17
142. Haynea W G, Web D J. The endothelin family of peptides: local horbiones with diverse role in health and disease. Clinical Science, 1993, 84 (5) : 485-500
143. Hernaders Renata, Ferro Jesus, Parecido Gonzales. Resistance to ascites syndrome, homoeothermic competence and levels of HSP70 in the heart and lung of broilers. 2002, 31 (3supplement) : 1442-1450
144. Herve Kempf, Charlotte Linares, Pierre Corvol and Jean-Marie Gasc. Pharmacological inactivation of the endothelin type A receptor in the early chick embryo: a model of mispatterning of the branchial arch derivatives. Development, 1998, 125, 4931-4941
145. Hill C S, Treisman R. Transcriptional regulation by extracellular signals: Mechamisms and specialty. Cell, 1995,80: 199
146. Hirata Y, Fukuda Y, Yoshimi H. Specific receptor for endothelin in cultured rat cardiocytes. Biochem Biophys Res Commun, 1989, 160 : 1438-1444
147. Hirata Y, Yoshimi M, Takata S. Cellular mechanism of action by a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells. Biochem Biophys Res Commun, 1988, 154:868-875
148. Hirata Y. Binding and receptor down-regulation of a novel vasoconstrictor endo thelin in cultured rat vascular smooth muscle cells. FEBS lett, 1988,293 : 13
149. Homma S, Maclcan M R, Mcculloch K M. Endotheline ETA and ETB reeeptor-mediated vasoconfriction in that pulmonary arteies and arterioles. J Candiocase Phamnacol, 1994, 23 : 838
150. Honing M L, Hijmering M L, Ballard D E. Selective ET (A) receptor antagonism with ABT-627 attenuates arenal effects of endothelin in humans. J Am Soc Nephrol, 2000, 11 (8) : 1498-1504
151. Huchzertmeye F W, De Ruych A M C. Pulmonary hypertension syndrome associated with ascites in broilers. Vet Rec, 1986, 119: 94
152. Igari H, Tatsumi K, Sugito K. Role of EDRF in pulmonary circulation during sustained hypoxia. Journal of Cardiovascular Pharmacology, 1998, 31 (2): 299-305
153. Inguimbert N, Poras H, Teffo F. N-[2- (indan-1-yl) -3-mercapto-propionyl] amino acids as highly potent inhibitors of the three vasopeptidases (NEP, ACE, ECE) : invitro and invivo activities. Bioorg Med Chem Lett, 2002, 12(15): 2001-2005
154. Inoue A, Yanagisawa M, Kimura S. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA, 1989,86:2863
155. Iqbal M D, D Cawthon, R. F. Wdeman, Jr, and W. G. Bottje. Lung mitochondria dysfunction in pulmonary hypertension syndrome I. Site-specific defects in the electron transport chain. Poultry Sci, 2001,80:485-495
156. Iscon T C, Vaclav H, Kenneth E. Increased endotheliun-derived NO in hypertensive pulmonary circulation of chronically hypoxic rats. J Appl Physiol, 1994, 76 ( 2) : 933
157. Ishikawa T, Yangisnwa M. positive inotropic action of novel uasocon8trictor peptide endothelin on quinea pig atria. Am J physiol, 1988, 255 : 970.
158. Ito H, Hirata Y, Adacnis etal. Endothelirrl is an auto crine factor in the myocar dium of cmgio fensin Ⅱ-induced hypertrophy in cultured rat cardio myocytsc. J clin Invest, 1993,92 : 398
159. Ito H, Hirata Y, Hiroe M. Endothelin-1 induces hypertrophy with eerhanced expression of muscle-specific geres in cultured neonatal rat cardio my ocytes. Cir Res, 1991, 69 : 209-215
160. Ito H, Hiroe M, HirataY. Endothelin a receptor antagonist (BQ123) blocks cardiac hypertrophy provoked by pressure overload. Circulation, 1994, 89 : 2198
161. Ito H, Hiroe Y, Adachi S. Endothelin-1 is an autocrine/ paracrine factor in the myocardium of angiotensin II-induced hypertrophy in cultured rat cardiomyocytes. J Clin Invest, 1993, 92 : 398-403
162. Iwasaki T, Mihara S, Shimamura T. Pharmacological characterization of ABSA, anorally active and highly potent endothelin receptor antagonist. J Cardiovasc Pharmacol, 1999, 34 (1) : 139-150
163. Janes R W, Peapus DH, Wallace B A. The crystal structure of human endothelin. Nat Struct Biol, 1994, 1 : 311-319
164. Jeng A Y, de Lombaert S, Beil M E. Design and synthesis of a potent and selective endothelin-converting enzyme inhibitor CGS35066. J Cardiovasc Pharmacol, 2000, 36 (5 Suppl 1): S36-39
165. Jeng A Y, Mulder P, Kwan A L. Nonpeptidic endothelin-converting enzyme inhibitors and their potential therapeutic applications. Can J Physiol Pharmacol, 2002, 80 (5) : 440-449
166. Julian R J. A scite in poultry. Avian Pathology, 1993, 22 : 419-454
167. Julian R J. Aascites in broiler chickens caused by pdeficient diets. A vian D isease, 1986, 30 : 453-459
168. Julian R J. Lung volume of meat-type chickens. Avian Disease, 1989, 33 : 174-176
169. Julian R J. Rapid growth problems: ascites and skeletel deformitiesin broilers. Poultry Science, 1998,77(12): 1773-1780
170. Julian R J. Right Ventricular hypertrophy, right ventricular failure and ascites in broiler chickens caused by amiodarone-induced lung pathology. Avian Pathology, 1989, 18 : 111-174
171. Julian R J. The effects of increased sodium in the drinking water on right ventricular failure and
ascites in broiler chickens. Avian Pathology, 1987, 16 : 61-71
172. Julian R J. The relationship of right ventricular hypertrophy, right ventricular failure, and ascites to weight gain in broiler and roaster chickens. Avian Diseases, 1987, 31 : 130-135
173. Julian R J. Physiological management and environmental triggers of the ascites syndrome. Poultry International July, 1998 (6): 28-33
174. Kanegaya Y, Oda M, Yokomori H. Role of endothelin receptor in endothelin-1-induced morphological changes of hepatic sinusoidal endothelin fenestrae: morphometric evaluation with scanning electron microscopy. Hepatol Res, 2002, 22 : 89-101
175. Kao J P, Harootunian A T, Tsien R Y. Photochemically generated cytosolic calcium pulses and their detection by fluo-3. J Biol Chem, 1989, 264 (14) : 817-819
176. Kimura S. Stmcture-activity relationship of endothelin, impotance of the cterminal moiety. Biochem Biophys Res Commum, 1988, 156 : 1182
177. Komurol, A. Endothelin Stimulate. C-fos and c-mys expession and proliferaction of uascular Smooth muscle. FEBS lett, 1988, 238 : 239
178. Kourembanas S, Marsden P A, McQuillan L P, Faller D V. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. The Journal of Clinical Investigation, 1991,88(3): 1054-1057
179. Kovitz K L, Aleskowirch T D, Sylvester J T, Flavahan N A. Endothelium derived contracting and relaxing factors contribute to hypoxic responses of pulmonary arteries. American Journal of Physiology, 1993, 265 : H1139-H1148
180. Lauer M R, Gunn M D, Clusin W T. Endothelin-1 activates a voltage-dependent Ca~(2+) current by a Gprotein-dependent mechanism in rabbit cardiac myocytes. J Physiol, 1992, 448 : 729-747
181.Lazurova I, Kramer H J. Endothelins-physiology, pathophysiology and importance in arterial hypertension. Vnitr Lek, 2000, 46 (10) : 719-723
182. Lee M E, Temizer D H, Clifford J A. Cloning of the GATA binding protein that regulate send othelinl gene expression in endothelial cells. J Biol Chem, 1991, 266 (24) : 16188-16192
183. Li De Pei, Fan zhen-zhong. Moclulatory effects of endothelin on carotid Bar or ellex in an esthetized rats. Acta physiologica Sinica, 1998, 50 (2) : 169
184. Loffler BM. Endothelin-converting enzyme inhibitors: current status and perspectives. J Cardiovasc Pharmacol, 2000, 35 (4 Suppl 2) : S79-82
185. Luciani N, de Rocquigncy H, Turcaccd S, et al. Highly sensitive and selective fluorescence assay for rapid screening of endothelin-con-verting enzyme inhibitors. Biochem J, 2001, 15(356): 813-819
186. Luger D. Erythropoiesis regulation during the development of ascites syndrome in broiler chickens: a possible role of corticosterone. J Anim Sci, 2003, 81 (3) : 784-90
187. Lunger dror, Shinder Dmitri, Yahav, Shlomo. Hyper-or hypothyroidism: its association with the development of ascites syndrome in fast-growing chickens. General and comparative endocrinology, 2002, 127 (3) : 293-299
188. Luo Zi qiang, Sun xiu hong. Modulation of endothelin-1 on pulmonary surfactant secretion. Acta physioloyica Sinca, 1998, 50 (3) : 333-336
189. Magazine H. Evaluation of endothelin receptor populations using endothelin-1 biotinylated at lysine-9 sidechain. Biochem Biophys Res Commun, 1991, 181 : 1245
190. Markewitz BA, Donald EK, Kohan E. Hypoxia decrease endothelin-1 synthesis by rat lung endothelial cells. Am J Physio, 1995,269 :215
191. Maxwell M H, Robertson G W. World broiler ascites survey 1996. Poultry International, 1997, 4 : 16-30
192. Maxwell M H, Robertson, Buutista. Apreliminary estimate of the heritability of plasma troponin T in broiler chickens. British Poultry Science, 1998, 39 : 16-19
193. Mcquillan L P, Leung G K, Marsden P A. Hypoxia inhibits expression of eNOS via transcriptional and posttranscriptional mechanisms. Amerian Journal of Physiology, 1994, 267 (5 Pt 2):H1921-1927
194. Mehta S, Stewart D J, Langleben D. Short-term pulmonary vasodilation with L-Arginine in pulmonary hypertension. Circulation, 1995, 92 (6): 1539-1545
195. Meluzzi A, Sirri F, Tailarico N. Nitrogen retention and performance of Brown laying hens on diets and erergy. Poultry Science, 2001, 80 (4): 485-495
196. Miyauchi T, Masaki T. Pathophysiology of endothelin in the cardiovascular system. Annu Rev Physiol, 1999,61 : 391-415
197. Miyauchi T, Yorikane R, Sakai S. Contribution of endogenous endothelin-1 to the rogression of cardiopulmonary alterations in rats with monocrotaline-induced pulmonary hypertension. Circle Research, 1993, 73 (7) : 887-897
198. Miyazaki H. Affinity labelling of endothelin recepor and characterization of solubilized endothelin-endothelin-receptor compelx. Eur J Biochem, 1990, 187(1): 125-129
199. Miyazaki H, Kondoh M, Watanabe H. Identification of the endothelin-1 receptor in the chick hear. J Cardiovasc Pharmacol, 1989, 13 (5) : 155-156
200. Moghadam, H. K., I. McMillan, J. R. Chambers, and R. J. Julian. Estimation of genetic parameters for ascites syndrome in broiler chickens. Poultry Sci. 2001, 80 : 844-848
201.Moncada S, Palmer R M. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev, 1991, 43 : 109-142
202. Morenode M Sandino, A. Hernandez. Ntric oxide synthase expression in the endothelium of pulmonary arterioles in normal and pulmonary hypertension chickens subjected to chronic hypobaric hypoxia. Avian Diseases, 2003, 47 : 1291-1293
203. Morris, Claudia R, Kuypers, Frans A. Arginase activity is elevated in patients with sickle cell disease and pulmonary hypertension. Blood, 2002, 100 (11) : 1755
204. Mulder P, Richard V, Derumeaux G. Role of endogenous endothelin in chronic heart failure. Effect of long-term treatment with an endothelin antagonist on survival, hemodynamics, and cardiac modelling. Circulation, 1997, 96 : 1976-1982
205. Neys L, Nouskas J, Luyken J. Induction of immediate-early gene by angiotensin II and endothelin-1 in adult rat cardiomyocytes. J Hypertension. 1993, 11 : 927-934
206. Nucci D G. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of Prostallylin and endotlelium derived relaxing factor. Droc Natt Acad Sci USA, 1988, 85 : 9797
207. Ocampo L, Cortez U, Sumano H, et al. Use of low doses of clenbuerol to reduce incidence of ascites syndrome in broilers. Poult Sci, 1998,77 (9): 1297-1299
208. Odom T W. Effect of vitro hypoxic and normoxic conditions in fast-and slow-growing chicken pulmonary arteries. Poult Sci, 1997, Suppl 76. 33-47
209. Odom T W. A scites syndrome: overview and update. Poultry Digest, 1993, (1): 14-22
210. Odom T W. In vitro vasoactivity of avian pulmonary arteries: Physiological implications of endothelium-derived relaxing factor. Poultry Science, 1995, 74 (Suppl) : 37
211. Odom T W. Use of electrocardiograph analysis for investigation of ascites syndrome in bro iler ch ickens. A vian D isease, 1991,35 : 738-744
212. Ohlstein E H, et al, Biosynthesis and modulation of endothelin from bovine pulmonary arterial endothelial cells. Life Sci 1990, 46 (3) : 181
213. Olkowski A A, Classen H L. Progressive bradycardia, a possible factor in the pathogenesis of ascites in fast growing broiler chickens at low altitude. British Poultry Science 1998, 39 : 139-146
214. Oparil S, Chen S J, Meng Q C. Endothlin-A receptor antagonist prevents acute hypoxia-induced pulmonary hypertension in the rat. Am J Physiol, 1995, 268 : L95-L100
215. Owen R L, Wideman B S. Effect of age of exposure and dietary acidification or alkalization on mo rtality due to bro iler pulmonary hypertension syndrome. J App I Poultry Research, 1994, 3 :\ 244-252
216. Pace D M, Aftonomos L, Arthur W M. 1959. Effect of trypsin on growth in several clones of tissue cells. J Natl Cancer Inst. 1959, 28 : 655-667
217. Pace D M, Layon M E. Effect of cell dnsity on growth in hela cell. Growth. 1960, 24 : 355-359
218. Pakdel A, Vanarendonk J A M, Vereijken A L J, Bovenhuis, H. Direct and maternal genetic effect for ascites-related traits in broilers . Poultry science, 2002, 81 (9) : 1273-1279
219. Palmer L A, Semenza G L, Stoler M H. Hypoxia induces type II NOS gene expression in pulmonary artery endothelial cells via HIF-1. Amerian Journal of Physiology, 1998, 274 (2 Pt 1): L212-219
220. Peacock A J. The relationship between rapid growth and pulmonary homodynamic in the fast growing broiler chickens. Am Rev Respir Dis, 1989, 139:15-24
221.Pnicke K, Vogelsang M, Heinroth M, et al. Endothelin receptors in the failing and nonfailing human heart. Circulation, 1998, 97 : 744-751
222. Richard J W, Currie M. Review of ascites in poultry: rncent investigation. Avian Pathology, 1999,28:313-326
223. Rman M F, Wideman R F. Renal responses of normal and preascitis broiler to systemic hypotension induced by unilateral pulmonary artery occlusion poultry science. 1999, 78 (12) : 1773-1785
224. Robert L, Vender M D. Chronic hypoxic pulmonary hypertension, cell biology to pathophysiology. Chest, 1994, 106 (1) : 236-243
225. Roush W B, Wideman R F, Cahaner A. Minimum number of chicken daily growth velocities for artificial neural network detection of PHS. Poultry Science, 2001, 80 (3) : 254-259
226. Rubanyi G M, Polokoff M A. Endothelin: molecular biology, biochemistry, pharmacology, physiology, and pathophysiology. Pharmacol Rev, 1994, 46 : 328-415
227. Ruben Walker. New conceptin ascites physiology. Poultry International, 1994, 19 : 48-51
228. Ruiz-feria A C, Kidd M T, Wideman R F. Plamsa levels ofarginine, ornithine, and urea and growth performance of broilers fed supplemental L-arginine during cool temperature exposure. Poultry Science, 2001, 80 (3): 358-369
229. Sakai S, Miyauchi T, Kobayashi T. Altered expression of isoforms of myosin heavy chain mRNA in the failing rat heart is amelio rated by chronic treatment with an endothelin receptor antagonist. J Cardiovasc Pharmacol, 1998; 31 (Suppl1): S302-S305
230. Sakai S, Miyauchi T, Sakurai T. 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, 3 (6): 1214-1222
231. Sakai S, Miyauchi T, Yamnguchi I. Long-term endothelin receptor antagonist administration improves alteration in expression of various cardiac genes in failing myocardium of rats with heart failure. Circulation, 2000, 101 :2849-2853
232. Schulze-Neick I, Li J, Reader J A. The endothelin antagonist BQ-123 reduces pulmonary vascular resistance after surgical intervention for congenital heart disease. J Thorac Cardiovasc Surg,2002, 124 (3): 435-441
233. Shanna AC, Motev S T, Farias S. Sepsis alters myocardial and plasma concentrations of endotheline and nitric oxide in rats. J Mol Cell Cardiol, 1997, 29 : 1469-1479
234. Shaw M D, Vermeulen M, M urray G D. Efficacy and safety of the endothelin receptor antagonist TAK-044 in treating subarachnoid hemorrhage : a report by the steering committee on behalf of the UK/N etherlands/Eire TAK-044 Subarachnoid Haemor-rhage Study Group. J Neurosurg, 2000, 93 (6) : 992-997
235. Shlosberg A and Bellaiche M. Hematocrit values and mortality from ascites in cold-stressed broilers from parents selected by hematocrit. Poultry Science, 1996, 75 : 1-5
236. Shlosberg A, Bendheim U, Berman E. The effects of poor ventilation, low temperatures, type of feed and sex of bird on the development of ascites in broilers. A vian Patho logy, 1992,21 : 369
237. Silversides. The effect of broiler on physiological parameters associated with the ascites syndrome. Poultry Science, 1997, 76 : 5, 663-667
238. Sogni P, Moreau R, Gomola A. Beneficial hemodynamic effects of bosentan, a mixed ET (A) and\ ET (B) recptor antagonist, in portal hypertensive rats. Hepatology, 1998, 28 (3) : 655-659
239. Spinella F, Rosano L, Di Castro V. Endothelin-1-induced prostaglandin E2-EP2, EP4 signaling regulates vascular endothelial growth factor production and ovarian carcinoma cell invasion. The Journal of Biological Chemistry, 2004,279 (45): 46700-46705
240. Steudel W, ScheDer-Crosbie M, Block K D. Sustained pulmonary hypertension and right ventricular hypertrophy after chronic hypoxia in mice with congenital deficiency of nitric oxide synthase3. Journal of Clinical Investigation. 1998, 101 (11) : 2468-2477
241. Steward D J, Levy R D, Cernacek P. Increased plasma endothelin-1 in pulmonary hypertension marker or mediator of disease. Am Intern Med, 1991, 114: 464-469
242. Swire P W. Ascites in broiler. Vet Rec, 1980, 107: 540
243. Tang C M, Presser F, Morad M. Amiloride selectively blocks the low threshold (T) calcium channel. Science, 1988, 240 : 213-215
244. Tholken R E, Ganten H D. Atrial natriuretic factor: a circulating hormone stimulated by volume loading. Nature, 1985, 314 :264-266
245. Torre-Amione G, Young J B, Durand J. Hemodynamic effects of tezosentan, an intravenous dual endothelin receptor antagonist, in patients with classⅢ to IV congestive heart failure. Circulation, 2001, 103 (7): 937-980
246. Trapani AJ, Beil M E, Bruseo C W. Pharmacological properties of CGS35066, a potent and selective endothelin-converting enzyme inhibitor, in conscious rats. J Cardiovasc Pharmacol, 2000, 36 (5 Suppl 1):S40-43
247. Trapani AJ, Lombaert S, Kuzmich S. Inhibition of big ET-1 induced pressor response by an orally active dual inhibitor of endothelin converting enzyme and neutral endopeptidase, 24. 11. J Cardiovasc Pharmacol, 1995,26 (Suppl 3): S69
248. Tsurumi Y, Fujie K, Nishiksura M. Biological and pharmacological properties of highly selective new endothelin converting enzyme inhibitor WS 79089 B, isolated from streptosporangium roseum NO79089. J Antibiotics, 1995,48 : 169
249. Tsurumi Y, Murohara T, Krasinski K. Reciprocal relation between VEGF and NO in the regulation of endothelial integrity. Nature Medicine, 1997,3 (8): 879-886
250. Umekawa K, Hasegawa H, Tsutsumi Y. Pharmacological characterization of a novel sulfonylureid pyrazole derivative, SM19712, a potent nonpeptidic inhibitor of endothelin converting enzyme. Jpn J Pharmacol, 2000,84 (1) : 7215
251. Undernood D C, Bochnowicz S, Osborn R R. Nonpeptide endothelin receptor antagonists. X. Inhibition of endothelin-1 and hypoxia-induced pulmonary pressor responses in the guinea pig by
the endothelin receptor antagonist, SB-17242. J P harmacol Exp Ther, 1997, 283(3), 1130-1137
252. Vanhooser S L, Beker A, Teeter R G. Broncholilator, oxygen level and temperature effects on ascites incidence in broiler chickens. Poultry Science, 1995, 74: 1586-1590
253. Vaxlav H, Jan H. Role of nitric oxide in the pathogenesis of chronic pulmonary hypertension. Physiological Reviews, 2000, 80(4): 1337-1372
254. Vender R L. Chronic hypoxic pulmonary hypertension. Cell biology to pathophysiology. Chest, 1994, 106(1): 236-243
255. Walter Bottije, Robert F, W ideman J R. Effect of tocopherol on antioxidants, lipid peroxidant, and the incidence of pulmonary hypertension sysndrome in broilers. Poultry Science, 1995, 74: 1356-1369.
256. Wang J X, Morgan J P. Endothelin reverses the effect of acidosis on the intracellular Ca~(2+) transient and contractility in ferret myocardium. Circ Res, 1992, 71: 631-639
257. Wang J, Wang X, Xiang R, Sun W. Effect of L-NAME on pulmonary arterial pressure, plasma nitric oxide and pulmonary hypertension syndrome morbidity in broilers. British Poultry Science, 2002, 43(4): 615-620
258. Wang J. Y. and Hacker R. R. Effects of diaoxinxuekang on ascites in broilers. Poultry Science, 1993, 72: 1467-1472
259. Wang J M, Shi Y D, Lian Z J. Influence of shearing stress to the expression of endothelin by vascular endothelial cellsl 生物化学与生物物理学报, 1999, 31(3): 298-302
260. Wang Y, Toyoda O. Involvement of endothelin-1 in hypoxic pulmonary vasoconstriction in the lamb. Journal of Physiology, 1995, 482(2): 421-434
261. Watanabe H, Miyazaki H, Kondoh M. Two distinct types of endothelin receptors are present on chick cardiac membranes. Biochemical and Biophysical Research Communications, 1989, 161(3): 1252-1259
262. Watson S, Arikinstall S. The G-proetin linked receptor factsbook: Tachykinins. London: Academic Press, 1994. 266-267
263. Webb D J. Endothelin: from molecule to man. Br J Pharmacol, 1997, 44: 9
264. Wei C M, Lerman A, Rodeheffer R J. Endothelin in human congestive heart failure. Circulation, 1994, 89: 1580-1586
265. Weidong S, Xiaolong W, Jinyong W. Pulmonary arterial pressure and electrocardiograms in broiler chickens infused intravenously with L-NAME, an inhibitor of nitric oxide synthase, or sodium nitroprusside (SNP), a nitric oxide donor. British Poultry Science, 2002, 43(2); 306-12
266. White D G, Cannon T R, Garratt H. Endothelin ETA and ETB receptors mediate vascular smooth muscle contraction. J Cardiovasc Pharmacol, 1993, 22(8): 144-148
267. Wideman R F, French H. Ascites resistance of progeny from broiler breeders selected for two generations using chronic unilateral pulmonary artery occlusion. Poultry science, 2000, 79(3): 396-401
268. Wideman R F, Erf G F, Chapman M E. Intravenous endotoxin triggers pulmonary vasoconstriction and pulmonary hypertension in broiler chickens. Poultry Science, 2001, 80: 647-655
269. Wideman R F, Fedde M R, Tackert C D. Cardio-pulmonary function in preascitic (hypoxemic) or normal broilers inhaling ambient air or 100% oxygen. Poultry Science, 2000, 79(3): 415-425
270. Wideman R F, Ismail M, Kirby Y K. Furosemide reduces the incidence of pulmonary hypertension syndrome (ascites) in broilers exposed to cool environmental temperatures. British Poultry Science, 1994, 35: 663-667
271. Wideman R F, Ismail M, Kiirb Y K. Furosemide reduces the incidence of pulmonary hypertension syndrome in bro ilers exposed to cool environmental temperature. Poultry Science, 1995,74:314-322
272. Wideman R F, Kirby Y K. Cardio-pulmonary function during acute unilateral occlusion of the pulmonary artery in broilers fed diets containing normal or high levels of arginine-HCL. Poultry Science, 1996,75 : 1587-1602
273. Wideman R F, Tackett C D. Cardio-pulmonary function in broilers reared at warm or cool temperatures : Effect of acute inhalation of 100% oxygen. Poultry Science, 2000, 79 : 257-264
274. Wideman R F. Electrocardiographic evaluation of broilers during the onset of pulmonary hypertension initiated by unilateral pulmonary artery occlusion. Poultry Science, 1996, 75 : 407-416
275. Wideman R F. Intravenous endothelin triggers pulmonary vasoconstriction and pulmonary hypertension in broiler chickens. Poultry Science, 2001, 80 : 647-655
276. Wideman R F. Measurements of pulmonary arterial pressure in anesthetized male bro ilers at two to seven week s of age. Poultry Science, 2000, 78 : 1645-1649
277. Wideman R F Jr, Kirby YK, Ismail M. Supplemental L-arginine attenuates pulmonary hypertension syndrome (ascites) in broilers. Poultry Science, 1995, 74 (2) : 323-330
278. Wideman R F, Howard French. Broiler survivors of chromic unilateral pulmonary artery occlusion produce progeny resistant to pulmonary hypertension syndrome induced by cool temperatures. Poultry Science, 1999, 78 (3) 404-411
279. Wideman R F, Yvonne Kochera Kirba. A pulmonary artery model for induces pulmonary hypertension syndrome in broilers. Poultry Science, 1995, (5): 805-812
280. Wideman RF. Gardio-pulmonary homodynamics and ascites in broiler chickens. Avian and Poultry Bidogy Reviews, 2000, 11(1) : 21-43
281. Wideman R F. Supplemental L-Argentine attenuates pulmonary hypertension syndrome tension syndrome in broiler. Poultry Science, 1995, 75 : 407
282. Wilson J. B. , Julian R. J. , Barker I. K., Lesions of right heart failure and ascites in broiler chickens. Avian Dis.,1988, 32, 246-261
283. Wu Bin, Wang Jing hua, Pan Jin yan. The role of G protein, protein Kinasecand Na~+-H~+ exchanger in endothelin-1-Induced cardiomy o cyte hypertrophic responses. Acta physvologica Sinica, 1991, 50 (1) : 87
284. Wu C, Decker E R, GeorgeW. Nonpeptide endothelin antagonists in clinical development. Drugs of Today, 2001, 37 (7) : 441-453
285. Xiang R P, Sun W D, Zhang K C. Sodium chloride-induced acute and chronic pulmonary hypertension syndrome in broiler chickens. Poultry Science, 2004, 83 (5): 732-736
286. Yamaguchi R, Tottori J, Vchida K. Importance of Escherichia coli infection in ascites in broiler chickens broiler chickensshown by experimental production. Avian disease, 2000, 44 (3) : 545-548
287. Yanagisawa M, Kurihara H, Kimura S. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature, 1988,332 (6163): 411-415
288. Yanagisawa M, Masakit. Edothelin, a novel endothelium derived peptide. Bioochem Pharmacol, 1989,38:1877
289. Yokokawa K, Kohno M, Murakawa K. Acute effects of endothelin on renal hemodynamics and blood pressure in anesthetezed rats. Am J Hypertens, 1989,2 (9): 715-717
290. Zamora M A, Dempsey E C, Walchak S J. BQ-123, 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) : 429-433
291. Zhang Zhao. Effects of endothelin on the electrical activity of sino-atrial pacemaker cells of Rubbit Acta Physiologica sinica, 1996, 48 (1) : 53
292. Zheng Hui-zhen. An Guo-shum, Nie Si-huai. Inhibition of signal transduction pathways of endothelin-1 induced proliferation of vascular smooth muscle cells by nitric oxide. Acta physiologica sinica, 1998, 50 (4): 339
293.Zoccali C, Leonardis D, Parkongo S. Urinary and plasma endothelin-1 in essential hypertension and in hypertion secondary to renoparenchyma disease. Nephrol Dial Transplant, 1995, 10(8): 1320