银杏苦内酯B对颈动脉窦压力感受性反射和压力感受器活动作用的研究
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摘要
银杏叶提取物(ginkgo biloba extract, GBE)是从银杏中提取的天然化合物,主要包括6%的萜内酯和24%的黄酮。银杏苦内酯B(ginkgolide B)是萜内酯类的一种主要活性物质。大量研究发现银杏苦内酯B为血小板活化因子的天然拮抗剂,并已在较大范围内展现出生物学活性。银杏苦内酯B可通过调节血流量、降低缺血再灌注损伤和抑制血小板凝集等药理作用,对心脑血管产生保护功效。银杏苦内酯B可引起血管舒张,但其作用机制尚不明确。有研究显示银杏苦内酯B可浓度依赖性的抑制L-型钙电流和部分减轻缺血再灌注过程中的钙超载。通过使用全细胞膜片钳技术证明了在心室肌细胞上银杏苦内酯B可浓度依赖性的缩短动作电位时程,主要与增大延迟整流型钾电流有关。由于压力感受器活动和反射在维持血压稳定方面起重要作用,而银杏苦内酯B对它们的影响至今无报道。因此本课题对以上两部分进行了研究:
1银杏苦内酯B对麻醉大鼠颈动脉窦压力感受性反射的作用
目的:旨在观察银杏苦内酯B对麻醉大鼠颈动脉窦压力感受性反射的作用。
方法:采用本实验室自行设计的实验程序,隔离灌流30只麻醉雄性大鼠的颈动脉窦区,同时记录动脉血压的变化,并绘制压力感受性反射的功能曲线。
结果:(1)银杏苦内酯B (ginkgolide B 0.1, 1, 10μmol/L)可以剂量依赖性的抑制大鼠颈动脉窦压力感受性反射,引起压力感受性反射的功能曲线向右上方移动,曲线斜率明显减小,血压反射性下降的幅度减小。曲线最大斜率(peak slop, PS)由对照时的0.46±0.01分别降至0.37±0.01,0.32±0.01,0.23±0.01。反射性血压下降幅度(reflex decrease, RD)由对照时的(46.50±1.38) mmHg分别降至(40.00±0.89),(34.83±1.94),(28.33±1.50) mmHg。阈压(threshold pressure, TP)由(65.46±1.76) mmHg分别增至(71.66±0.84),(75.18±1.56),(84.56±1.76) mmHg;平衡压(equilibrium pressure, EP)由(93.94±0.82) mmHg分别增至(96.28±1.10),(98.29±0.90),(100.64±1.01) mmHg ;饱和压(saturation pressure, SP)由(186.33±2.73) mmHg分别增至(192.00±2.37),(195.83±2.04),(205.17±2.14) mmHg。(2)预先应用钙通道的开放剂Bay K8644 (500 nmol/L),可以完全取消银杏苦内酯B的抑制作用。(3)预先应用钾通道的阻断剂四乙胺(tetraethylammonium, TEA, 1 mmol/L),银杏苦内酯B的上述作用也被完全取消。
结论:银杏苦内酯B对大鼠颈动脉窦压力感受性反射有抑制作用,此作用与银杏苦内酯B减少颈动脉窦压力感受器神经末梢钙离子内流和增加钾离子外流有关。
2银杏苦内酯B对麻醉大鼠颈动脉窦压力感受器活动的作用
目的:本文旨在观察银杏苦内酯B对大鼠颈动脉窦压力感受器活动的影响。
方法:采用本实验室自行设计的实验程序及记录方法,隔离灌流30只麻醉雄性大鼠颈动脉窦区,记录窦神经放电,并绘制压力感受器活动的机能曲线。
结果:(1)银杏苦内酯B (ginkgolide B 0.1, 1, 10μmol/L)可以剂量依赖性的抑制大鼠颈动脉窦压力感受器的活动,引起压力感受器活动的机能曲线向右下方移动,曲线最大斜率明显减小,窦神经放电的最大积分值显著下降。曲线最大斜率(peak slop, PS)由对照时的(3.08±0.11) %mmHg-1,分别降至(2.52±0.06),(2.22±0.05),(2.00±0.07) %mmHg-1。最大积分值(PIV)由(331.17±3.76) %分别降至(273.67±4.03), (243.67±3.72),(213.67±5.16) %;阈压(threshold pressure, TP)由(44.16±1.50) mmHg分别增至(51.81±1.28),(58.67±3.02),(63.42±1.44) mmHg;饱和压(saturation pressure, SP)由(161.33±2.07) mmHg分别增至(172.33±1.03),(181.33±2.16),(188.17±1.17) mmHg。(2)预先应用钙通道的开放剂Bay K8644 (500 nmol/L),可以完全取消银杏苦内酯B的抑制作用。( 3 )预先应用钾通道的阻断剂四乙胺(tetraethylammonium, TEA, 1 mmol/L),银杏苦内酯B的上述作用也被完全取消。
结论:银杏苦内酯B对大鼠颈动脉窦压力感受器活动有抑制作用,此作用与银杏苦内酯B减少颈动脉窦压力感受器神经末梢钙离子内流和增加钾离子外流有关。
Ginkgo biloba extract (GBE) is a natural compound derived from the Ginkgo biloba and mainly composed of 6% terpene lactones and 24% flavonol glycosides. Ginkgolide B is a major active component of terpene lactones. Numerous studies have showed ginkgolide B, a potent antagonist of platelet-activating factor, exhibits a wide range of biological effects. Ginkgolide B has been used for cardiovascular and cerebrovascular disease by improving blood flow, reducing ischemia-reperfusion injury or inhibiting platelets. Ginkgolide B produces vasorelaxation, but the mechanism of ginkgolide B on vascular smooth muscles function is still essentially unknown. Some other experiments have already demonstrated that ginkgolide B decreases L-type calcium current (ICa,L) in a concentration-dependent manner and partially inhibits calcium overload during ischemia. Ginkgolide B may shorten the action potential duration in a concentration-dependent manner which mainly due to the increase of the delayed rectifier potassium current (Ik) in single ventricular myocytes by using patch-clamp techniques. It is well known that baroreflex is a major way to modulate blood pressure. The effects of ginkgolide B on carotid sinus baroreceptor activity and baroreflex have not been reported yet; the goals of the present research were to observe these effects of ginkgolide B.
1 Effects of ginkgolide B on carotid sinus baroreflex in anesthetized male rats
Objective: To study the effects of ginkgolide B on carotid sinus baroreflex (CSB).
Methods: The functional curve of carotid sinus baroreflex was measured by recording the changes of arterial pressure in 30 anesthetized male rats with isolated perfusing carotid sinus.
Results: (1) ginkgolide B (0.1, 1, 10μmol/L) inhibited CSB, which shifted the functional curve of the baroreflex to the right and upward, with a marked decrease in peak slope (PS) and reflex decrease (RD) in blood pressure in a concentration-dependent manner. PS decreased from 0.46±0.01 to 0.37±0.01, 0.32±0.01, 0.23±0.01 respectively. RD decreased from (46.50±1.38) mmHg to (40.00±0.89), (34.83±1.94), (28.33±1.50) mmHg; threshold pressure (TP) increased from (65.46±1.76) mmHg to (71.66±0.84), (75.18±1.56), (84.56±1.76) mmHg; equilibrium pressure (EP) increased from (93.94±0.82) mmHg to (96.28±1.10), (98.29±0.90), (100.64±1.01) mmHg; saturation pressure (SP) increased from (186.33±2.73) mmHg to (192.00±2.37), (195.83±2.04), (205.17±2.14) mmHg respectively. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1μmol/L) on the CSB. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium current, completely abolished the above effects of ginkgolide B (1μmol/L) on CSB.
Conclusion: Ginkgolide B inhibits the CSB in anesthetized male rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve ending.
2 Effects of ginkgolide B on carotid sinus baroreceptor activity in anesthetized male rats
Objective: To study the effects of ginkgolide B on carotid baroreceptor activity (CBA).
Methods: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in 30 anesthetized male rats with perfused isolated carotid sinus.
Results: (1) ginkgolide B (0.1, 1, 10μmol/L) inhibits CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. PS decreased from (3.08±0.11) %mmHg-1 to (2.52±0.06), (2.22±0.05), (2.00±0.07) %mmHg-1, respectively. PIV decreased from (331.17±3.76) % to (273.67±4.03), (243.67±3.72), (213.67±5.16) %, respectively; threshold pressure (TP) increased from (44.16±1.50) mmHg to (51.81±1.28), (58.67±3.02), (63.42±1.44) mmHg; saturation pressure (SP) increased from (161.33±2.07) mmHg to (172.33±1.03), (181.33±2.16), (188.17±1.17) mmHg. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1μmol/L) on CBA. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium current, completely abolished the above effects of ginkgolide B (1μmol/L) on CBA.
Conclusion: Ginkgolide B inhibits CBA in anesthetized male rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve ending.
1银杏苦内酯B对麻醉大鼠颈动脉窦压力感受性反射的作用
目的:旨在观察银杏苦内酯B对麻醉大鼠颈动脉窦压力感受性反射的作用。
方法:采用本实验室自行设计的实验程序,隔离灌流30只麻醉雄性大鼠的颈动脉窦区,同时记录动脉血压的变化,并绘制压力感受性反射的功能曲线。
结果:(1)银杏苦内酯B (ginkgolide B 0.1, 1, 10μmol/L)可以剂量依赖性的抑制大鼠颈动脉窦压力感受性反射,引起压力感受性反射的功能曲线向右上方移动,曲线斜率明显减小,血压反射性下降的幅度减小。曲线最大斜率(peak slop, PS)由对照时的0.46±0.01分别降至0.37±0.01,0.32±0.01,0.23±0.01。反射性血压下降幅度(reflex decrease, RD)由对照时的(46.50±1.38) mmHg分别降至(40.00±0.89),(34.83±1.94),(28.33±1.50) mmHg。阈压(threshold pressure, TP)由(65.46±1.76) mmHg分别增至(71.66±0.84),(75.18±1.56),(84.56±1.76) mmHg;平衡压(equilibrium pressure, EP)由(93.94±0.82) mmHg分别增至(96.28±1.10),(98.29±0.90),(100.64±1.01) mmHg ;饱和压(saturation pressure, SP)由(186.33±2.73) mmHg分别增至(192.00±2.37),(195.83±2.04),(205.17±2.14) mmHg。(2)预先应用钙通道的开放剂Bay K8644 (500 nmol/L),可以完全取消银杏苦内酯B的抑制作用。(3)预先应用钾通道的阻断剂四乙胺(tetraethylammonium, TEA, 1 mmol/L),银杏苦内酯B的上述作用也被完全取消。
结论:银杏苦内酯B对大鼠颈动脉窦压力感受性反射有抑制作用,此作用与银杏苦内酯B减少颈动脉窦压力感受器神经末梢钙离子内流和增加钾离子外流有关。
2银杏苦内酯B对麻醉大鼠颈动脉窦压力感受器活动的作用
目的:本文旨在观察银杏苦内酯B对大鼠颈动脉窦压力感受器活动的影响。
方法:采用本实验室自行设计的实验程序及记录方法,隔离灌流30只麻醉雄性大鼠颈动脉窦区,记录窦神经放电,并绘制压力感受器活动的机能曲线。
结果:(1)银杏苦内酯B (ginkgolide B 0.1, 1, 10μmol/L)可以剂量依赖性的抑制大鼠颈动脉窦压力感受器的活动,引起压力感受器活动的机能曲线向右下方移动,曲线最大斜率明显减小,窦神经放电的最大积分值显著下降。曲线最大斜率(peak slop, PS)由对照时的(3.08±0.11) %mmHg-1,分别降至(2.52±0.06),(2.22±0.05),(2.00±0.07) %mmHg-1。最大积分值(PIV)由(331.17±3.76) %分别降至(273.67±4.03), (243.67±3.72),(213.67±5.16) %;阈压(threshold pressure, TP)由(44.16±1.50) mmHg分别增至(51.81±1.28),(58.67±3.02),(63.42±1.44) mmHg;饱和压(saturation pressure, SP)由(161.33±2.07) mmHg分别增至(172.33±1.03),(181.33±2.16),(188.17±1.17) mmHg。(2)预先应用钙通道的开放剂Bay K8644 (500 nmol/L),可以完全取消银杏苦内酯B的抑制作用。( 3 )预先应用钾通道的阻断剂四乙胺(tetraethylammonium, TEA, 1 mmol/L),银杏苦内酯B的上述作用也被完全取消。
结论:银杏苦内酯B对大鼠颈动脉窦压力感受器活动有抑制作用,此作用与银杏苦内酯B减少颈动脉窦压力感受器神经末梢钙离子内流和增加钾离子外流有关。
Ginkgo biloba extract (GBE) is a natural compound derived from the Ginkgo biloba and mainly composed of 6% terpene lactones and 24% flavonol glycosides. Ginkgolide B is a major active component of terpene lactones. Numerous studies have showed ginkgolide B, a potent antagonist of platelet-activating factor, exhibits a wide range of biological effects. Ginkgolide B has been used for cardiovascular and cerebrovascular disease by improving blood flow, reducing ischemia-reperfusion injury or inhibiting platelets. Ginkgolide B produces vasorelaxation, but the mechanism of ginkgolide B on vascular smooth muscles function is still essentially unknown. Some other experiments have already demonstrated that ginkgolide B decreases L-type calcium current (ICa,L) in a concentration-dependent manner and partially inhibits calcium overload during ischemia. Ginkgolide B may shorten the action potential duration in a concentration-dependent manner which mainly due to the increase of the delayed rectifier potassium current (Ik) in single ventricular myocytes by using patch-clamp techniques. It is well known that baroreflex is a major way to modulate blood pressure. The effects of ginkgolide B on carotid sinus baroreceptor activity and baroreflex have not been reported yet; the goals of the present research were to observe these effects of ginkgolide B.
1 Effects of ginkgolide B on carotid sinus baroreflex in anesthetized male rats
Objective: To study the effects of ginkgolide B on carotid sinus baroreflex (CSB).
Methods: The functional curve of carotid sinus baroreflex was measured by recording the changes of arterial pressure in 30 anesthetized male rats with isolated perfusing carotid sinus.
Results: (1) ginkgolide B (0.1, 1, 10μmol/L) inhibited CSB, which shifted the functional curve of the baroreflex to the right and upward, with a marked decrease in peak slope (PS) and reflex decrease (RD) in blood pressure in a concentration-dependent manner. PS decreased from 0.46±0.01 to 0.37±0.01, 0.32±0.01, 0.23±0.01 respectively. RD decreased from (46.50±1.38) mmHg to (40.00±0.89), (34.83±1.94), (28.33±1.50) mmHg; threshold pressure (TP) increased from (65.46±1.76) mmHg to (71.66±0.84), (75.18±1.56), (84.56±1.76) mmHg; equilibrium pressure (EP) increased from (93.94±0.82) mmHg to (96.28±1.10), (98.29±0.90), (100.64±1.01) mmHg; saturation pressure (SP) increased from (186.33±2.73) mmHg to (192.00±2.37), (195.83±2.04), (205.17±2.14) mmHg respectively. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1μmol/L) on the CSB. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium current, completely abolished the above effects of ginkgolide B (1μmol/L) on CSB.
Conclusion: Ginkgolide B inhibits the CSB in anesthetized male rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve ending.
2 Effects of ginkgolide B on carotid sinus baroreceptor activity in anesthetized male rats
Objective: To study the effects of ginkgolide B on carotid baroreceptor activity (CBA).
Methods: The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in 30 anesthetized male rats with perfused isolated carotid sinus.
Results: (1) ginkgolide B (0.1, 1, 10μmol/L) inhibits CBA, which shifted FCCB to the right and downward. There was a marked decrease in peak slope (PS) and peak integral value (PIV) of carotid sinus nerve charge in a concentration-dependent manner. PS decreased from (3.08±0.11) %mmHg-1 to (2.52±0.06), (2.22±0.05), (2.00±0.07) %mmHg-1, respectively. PIV decreased from (331.17±3.76) % to (273.67±4.03), (243.67±3.72), (213.67±5.16) %, respectively; threshold pressure (TP) increased from (44.16±1.50) mmHg to (51.81±1.28), (58.67±3.02), (63.42±1.44) mmHg; saturation pressure (SP) increased from (161.33±2.07) mmHg to (172.33±1.03), (181.33±2.16), (188.17±1.17) mmHg. (2) Pretreatment with Bay K8644 (500 nmol/L), an agonist of L-type calcium channel, completely eliminated the effects of ginkgolide B (1μmol/L) on CBA. (3) Pretreatment with tetraethylammonium (TEA, 1 mmol/L), an inhibitor of potassium current, completely abolished the above effects of ginkgolide B (1μmol/L) on CBA.
Conclusion: Ginkgolide B inhibits CBA in anesthetized male rats, which is mediated by decreased calcium influx and increased potassium efflux in baroreceptor nerve ending.
引文
1 Briskin DP. Medicinal plants and phytomedicines. Linking plant biochemistry and physiology to human health. Plant Physiol, 2000, 124: 507-514
2 Kleijnen J, Knipschild P. Ginkgo biloba. Lancet, 1992, 340: 1136-1139
3 Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev, 2000, 80: 1669-1699
4 Wang SJ, Chen HH. Ginkgolide B, a constituent of Ginkgo biloba, facilitates glutamate exocytosis from rat hippocampal nerve terminals. Eur J Pharmacol, 2005, 514: 141-149
5 Debek W, Chyczewski L, Makarewicz M. Platelet-activating factor receptor-antagonist (BN 52021) stabilizes the oxidative-antioxidative balance and attenuates the morphological changes in the gastrointestinal tract inexperimental hemorrhagic shock. Exp Toxicol Pathol, 1998, 50: 19-25
6 Sneddon AA, McLeod E, Wahle KW, et al. Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: suppression by conjugated linoleic acid. Biochim Biophys Acta, 2006, 1761: 793-801
7 Flores NA, Goulielmos NV, Seghatchian MJ, et al. Myocardial ischaemia induces platelet activation with adverse electrophysiological and arrhythmogenic effects. Cardiovasc Res, 1994, 28: 1662-1671
8 Valli G, Giardina EG. Benefits, adverse effects and drug interactionsof herbal therapies with cardiovascular effects. J Am Coll Cardiol, 2002, 39: 1083-1095
9 Satoh H, Nishida S. Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles. Clin Chim Acta, 2004, 342: 13-22
10 Yang LZ, Zhang Y, Li JX, et al. Effects of BN-52021 on AP and L-type calcium channel in guinea pig’s ventricular myocytes. Chin Pharmaco Bull, 2002, 16: 195-198
11 Zhang ZX, Qi XY, Xu YQ. Effect of ginkgolide B on L-type calcium current and cytosolic [Ca2+] in guinea pig ischemic ventricular myocytes. Acta Physiol Sin, 2003, 55: 24-28
12 Qi XY, Zhang ZX, Xu YQ. Effects of Ginkgolide B on action potential and calcium, potassium current in guinea pig ventricular myocytes. Acta Pharmacol Sin, 2004, 25:203-207
13 Xu JP, Li L, Sun LS. Effects of ginkgolide on cerebral blood flow in dogs. J Chin Integr Med, 2005, 3: 50-53
14 Lopes-Martins R, Catelli M, Araújo C, et al. Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure. Eur J Pharmacol, 1996, 308: 287-294
15 Zhao G, He RR. The facilitating effect of atrial natriuretic peptide on the carotid sinus baroreflex function. Chin J Physiol Sci, 1993, 9: 68-75
16 Yi XL, Fan ZZ, He RR. An automatic system controlled by computer for carotid sinus perfusion. Chin J Appl Physiol, 1993, 9: 156-159
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19 Liu YX, Zhang H, Ma HJ, et al. Cholecystokinin octapeptide inhibits carotid sinus baroreflex in anesthetized rats. Acta Physiol Sin, 2004, 56: 25-30
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21 Matsuda T, Bates JN, Lewis SJ, et al. Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine. Circ Res, 1995, 76: 426-433
22 De Smet PA. Herbal remedies. N Engl J Med, 2002, 347: 2046-2056
23 Robert M, Matthew N. Cardiovascular Physiology. 1th ed. Beijing: Health Science Asia, Elsevier Science, 2002, 189-190
1 Kleijnen J, Knipschild P. Ginkgo biloba. Lancet, 1992, 340: 1136-1139
2 Briskin DP. Medicinal plants and phytomedicines. Linking plant biochemistry and physiology to human health. Plant Physiol, 2000, 124: 507-514
3 Wang SJ, Chen HH. Ginkgolide B, a constituent of Ginkgo biloba, facilitates glutamate exocytosis from rat hippocampal nerve terminals. Eur J Pharmacol, 2005, 514: 141-149
4 Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev, 2000, 80: 1669-1699
5 Nishida S, Satoh H. Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract. Clin Chim Acta, 2004, 339:129-133
6 Valli G, Giardina EG. Benefits, adverse effects and drug interactions of herbal therapies with cardiovascular effects. JAm Coll Cardiol, 2002, 39: 1083-1095
7 Satoh H, Nishida S. Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles. Clin Chim Acta, 2004, 342: 13-22
8 Yang LZ, Zhang Y, Li JX, et al. Effects of BN-52021 on AP and L-type calcium channel in guinea pig’s ventricular myocytes. Chin Pharmaco Bull, 2002, 16: 195-198
9 Kim J, Li Q, Fang CX, et al. Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in normal and high-glucose environments. Acta Pharmacol Sin, 2006, 27: 536-542
10 Qi XY, Zhang ZX, Xu YQ. Effects of Ginkgolide B on action potential and calcium, potassium current in guinea pig ventricular myocytes. Acta Pharmacol Sin, 2004, 25: 203-207
11 Xu JP, Li L, Sun LS. Effects of ginkgolide on cerebral blood flow in dogs. J Chin Integr Med, 2005, 3: 50-53
12 Lopes-Martins R, Catelli M, Araújo C, et al. Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure. Eur J Pharmacol, 1996, 308: 287-294
13 Zhao G, He RR. The facilitating effect of atrial natriuretic peptide on the carotid sinus baroreflex function. Chin J Physiol Sci, 1993, 9: 68-75
14 Yi XL, Fan ZZ, He RR. An automatic system controlled by computer for carotid sinus perfusion. Chin J Appl Physiol,1993, 9: 156-159
15 Kraske S, Cunningham JT, Hajduczok G, et al. Mechanosensitive ion channels in putative aortic baroreceptor neurons. Am J Physiol, 1998, 275: 1497-1501
16 Chapleau MW, Abboud FM. Modulation of baroreceptor activity by ionic and paracrine mechanisms: an overview. Braz J Med Biol Res, 1994, 27:1001-1015
17 Xue HM, Wu YM, Xiao L, et al. Effect of resveratrol on baroreceptor activity of carotid sinus in anesthetized male rats. Acta Pharm Sin, 2004, 56: 25-30
18 Schild JH, Clark JW, Hay M, et al. A- and C-type rat nodose sensory neurons: model interpretations of dynamic discharge characteristics. J Neurophysiol, 1994, 71: 2338-2358
19 Matsuda T, Bates JN, Lewis SJ, et al. Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine. Circ Res, 1995, 76: 426-433
20 Robert M, Matthew N. Cardiovascular Physiology. 1th ed. Beijing: Health Science Asia, Elsevier Science, 2002: 190-196
1 Jos Kleijnen, Paul Knipschild. Ginkgo biloba. Lancet, 1992, 340: 1136-1139
2 Xia SH, Fang DC. Pharmacological action and mechanisms of ginkgolide B. Chin Med J, 2007, 120: 922-928
3 Lopes-Martins R, Catelli M, Araújo C, et al. Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure. Eur J Pharmacol, 1996, 308: 287-294
4 Marrache AM, Gobeil F Jr, Bernier SG, et al. Proinflammatory gene induction by platelet-activating factor mediated via its cognate nuclear receptor. J Immunol, 2002, 169: 6474-6481
5 Giuseppe Montrucchio, Giuseppe Alloatti, Giovanni Camussi. Role of platelet-ativating factor in cardiovascular pathophysiology. Physiol Rev, 2000, 80: 287-294
6 Hosford D, Braquet P. Antagonists of Platelet-Activating Factor: Chemistry, Pharmacology and Clinical Applications. Prog Med Chem, 1990, 27: 325-380
7 Dhainaut JF, Tenaillon A, Hemmer M, et al. Confirmatory platelet-activating factor receptor antagonist trial in patients with severe gram-negative bacterial sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. BN 52021 Sepsis Investigator Group. Crit Care Med, 1998, 26: 1963-1971
8 Nishida S, Satoh H. Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract. Clin Chim Acta, 2004, 339: 129-133
9 Satoh H, Nishida S. Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles. Clin Chim Acta, 2004, 342: 13-22
10 Yang Hui, Xu Yongjian, Zhang Zhenxiang. The effect of ginkgo biloba on hypoxic pulmonary hypertension and the role of protein kinase C. Chin J of Tuberc Respir Dis, 2000, 23: 602-605
11 Ji Ningdong, Wei Enhuei, Cheng Qi. Effects of ginkgolides on cell proliferation induced by angiotensinⅡin cultured calf vascular smooth muscle cells. Jiangsu Med J, 2001, 27: 747-748
12 Liebgott T, Miollan M, Berchadsky Y, et al. Complementary cardioprotective effects of flavonoid metabolites and terpenoid constituents of Ginkgo biloba extract (EGb 761) during ischemia and reperfusion. Basic Res Cardiol, 2000, 95: 368-377
13 Pietri S, Maurelli E, Drieu K, et al. Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761). J Mol Cell Cardiol, 1997, 29: 33-42
14 Zhang Zhixiong, Qi Xiaoyan, Xu Youqiu. Effect of ginkgolide B on L-type calcium current and cytosolic [Ca2+]i in guinea pig ischemic ventricular myocytes. Acta Physiol Sin, 2003, 55: 24-28
15 Zhang Genbao, Chen Dongyun, Gui Cangqing. Experimental study on protective effect of ginkgolide B on isolated rats' hearts with ischemia-reperfusion. Chin J of Trad Med Sci and Tech, 2005, 12: 92-94
16 Gao Jian, Wang Qiujuan, Tang Yu, et al. Effect of ginkgolides on myocardial ischemic injury induced by isoprenaline. Tradi Chin Drug Res & Clin Pharma, 2004,
15: 151-155
17 Moore JM, Earnest MA, DiSimone AG, et al. A PAF receptor antagonist, BN 52021, attenuates thromboxane release and improves survival in lethal canine endotoxemia. Circ Shock, 1991, 35: 53-59
18 Cheng D, Chen W. Effects of ginkgolide B on isobarichypoxic pulmonary hypertension in rats. Chin Med J, 1996, 109: 881-884
19 Li DZ, Sharma R, Zeng QT. Effects of Ginkgo leaf extract on function of dendritic cells and Th1/Th2 cytokines in patients with unstable angina pectoris. Chin J Integr Med, 2005, 11: 260-263
20 Nemcsik J, Kordás K, Egresits J, et al. Synergistic interaction of endogenous platelet-activating factor and vasopressin in generating angina in rats. Eur J Pharmacol, 2004, 13: 195-202
21 Chopra K, Singh M, Gupta S, et al. Involvement of oxygen free radicals in the action of BN 52021 (PAF antagonist) to limit myocardial infarct size. Methods Find Exp Clin Pharmacol, 1993, 15: 437-445
22 Chakrabarty S, Thomas P, Sheridan DJ. Contribution of platelets and platelet-activating factor (PAF) to the arrhythmogenic, haemodynamic and necrotic effects of acute myocardial ischaemia. Eur Heart J, 1991, 12: 583-589
23 Maruyama M, Farber NE, Vercellotti GM, et al. Evidence for a role of platelet activating factor in the pathogenesis of irreversible but not reversible myocardial injury after reperfusion in dogs. Am Heart J, 1990, 120: 510-520
24 Qi Xiaoyan, Zhang Zhixiong, Cui Qiqi, et al. The effect of ginkgolide B on action potential, L-type calcium current and delayed rectifier potassium current in ischemic guineapig ventricular myocytes. Chin J Appl Physiol, 2004, 20: 24-28
25 Yang LZ, Zhang Y, Li JX, et al. Effects of BN-52021 on AP and L-type calcium channel in guinea pig’s ventricular myocytes. Chin Pharmaco Bull, 2002, 16: 195-198
2 Kleijnen J, Knipschild P. Ginkgo biloba. Lancet, 1992, 340: 1136-1139
3 Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev, 2000, 80: 1669-1699
4 Wang SJ, Chen HH. Ginkgolide B, a constituent of Ginkgo biloba, facilitates glutamate exocytosis from rat hippocampal nerve terminals. Eur J Pharmacol, 2005, 514: 141-149
5 Debek W, Chyczewski L, Makarewicz M. Platelet-activating factor receptor-antagonist (BN 52021) stabilizes the oxidative-antioxidative balance and attenuates the morphological changes in the gastrointestinal tract inexperimental hemorrhagic shock. Exp Toxicol Pathol, 1998, 50: 19-25
6 Sneddon AA, McLeod E, Wahle KW, et al. Cytokine-induced monocyte adhesion to endothelial cells involves platelet-activating factor: suppression by conjugated linoleic acid. Biochim Biophys Acta, 2006, 1761: 793-801
7 Flores NA, Goulielmos NV, Seghatchian MJ, et al. Myocardial ischaemia induces platelet activation with adverse electrophysiological and arrhythmogenic effects. Cardiovasc Res, 1994, 28: 1662-1671
8 Valli G, Giardina EG. Benefits, adverse effects and drug interactionsof herbal therapies with cardiovascular effects. J Am Coll Cardiol, 2002, 39: 1083-1095
9 Satoh H, Nishida S. Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles. Clin Chim Acta, 2004, 342: 13-22
10 Yang LZ, Zhang Y, Li JX, et al. Effects of BN-52021 on AP and L-type calcium channel in guinea pig’s ventricular myocytes. Chin Pharmaco Bull, 2002, 16: 195-198
11 Zhang ZX, Qi XY, Xu YQ. Effect of ginkgolide B on L-type calcium current and cytosolic [Ca2+] in guinea pig ischemic ventricular myocytes. Acta Physiol Sin, 2003, 55: 24-28
12 Qi XY, Zhang ZX, Xu YQ. Effects of Ginkgolide B on action potential and calcium, potassium current in guinea pig ventricular myocytes. Acta Pharmacol Sin, 2004, 25:203-207
13 Xu JP, Li L, Sun LS. Effects of ginkgolide on cerebral blood flow in dogs. J Chin Integr Med, 2005, 3: 50-53
14 Lopes-Martins R, Catelli M, Araújo C, et al. Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure. Eur J Pharmacol, 1996, 308: 287-294
15 Zhao G, He RR. The facilitating effect of atrial natriuretic peptide on the carotid sinus baroreflex function. Chin J Physiol Sci, 1993, 9: 68-75
16 Yi XL, Fan ZZ, He RR. An automatic system controlled by computer for carotid sinus perfusion. Chin J Appl Physiol, 1993, 9: 156-159
17 Kraske S, Cunningham JT, Hajduczok G, et al. Mechanosensitive ion channels in putative aortic baroreceptor neurons. Am J Physiol, 1998, 275: 1497-1501
18 Cunningham JT, Wachtel RE, Abboud FM. Mechanical stimulation of neurites generates an inward current in putative aortic baroreceptor neurons in vitro. Brain Res, 1997, 757: 149-154
19 Liu YX, Zhang H, Ma HJ, et al. Cholecystokinin octapeptide inhibits carotid sinus baroreflex in anesthetized rats. Acta Physiol Sin, 2004, 56: 25-30
20 Schild JH, Clark JW, Hay M, et al. A- and C-type rat nodose sensory neurons: model interpretations of dynamic discharge characteristics. J Neurophysiol, 1994, 71: 2338-2358
21 Matsuda T, Bates JN, Lewis SJ, et al. Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine. Circ Res, 1995, 76: 426-433
22 De Smet PA. Herbal remedies. N Engl J Med, 2002, 347: 2046-2056
23 Robert M, Matthew N. Cardiovascular Physiology. 1th ed. Beijing: Health Science Asia, Elsevier Science, 2002, 189-190
1 Kleijnen J, Knipschild P. Ginkgo biloba. Lancet, 1992, 340: 1136-1139
2 Briskin DP. Medicinal plants and phytomedicines. Linking plant biochemistry and physiology to human health. Plant Physiol, 2000, 124: 507-514
3 Wang SJ, Chen HH. Ginkgolide B, a constituent of Ginkgo biloba, facilitates glutamate exocytosis from rat hippocampal nerve terminals. Eur J Pharmacol, 2005, 514: 141-149
4 Montrucchio G, Alloatti G, Camussi G. Role of platelet-activating factor in cardiovascular pathophysiology. Physiol Rev, 2000, 80: 1669-1699
5 Nishida S, Satoh H. Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract. Clin Chim Acta, 2004, 339:129-133
6 Valli G, Giardina EG. Benefits, adverse effects and drug interactions of herbal therapies with cardiovascular effects. JAm Coll Cardiol, 2002, 39: 1083-1095
7 Satoh H, Nishida S. Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles. Clin Chim Acta, 2004, 342: 13-22
8 Yang LZ, Zhang Y, Li JX, et al. Effects of BN-52021 on AP and L-type calcium channel in guinea pig’s ventricular myocytes. Chin Pharmaco Bull, 2002, 16: 195-198
9 Kim J, Li Q, Fang CX, et al. Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in normal and high-glucose environments. Acta Pharmacol Sin, 2006, 27: 536-542
10 Qi XY, Zhang ZX, Xu YQ. Effects of Ginkgolide B on action potential and calcium, potassium current in guinea pig ventricular myocytes. Acta Pharmacol Sin, 2004, 25: 203-207
11 Xu JP, Li L, Sun LS. Effects of ginkgolide on cerebral blood flow in dogs. J Chin Integr Med, 2005, 3: 50-53
12 Lopes-Martins R, Catelli M, Araújo C, et al. Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure. Eur J Pharmacol, 1996, 308: 287-294
13 Zhao G, He RR. The facilitating effect of atrial natriuretic peptide on the carotid sinus baroreflex function. Chin J Physiol Sci, 1993, 9: 68-75
14 Yi XL, Fan ZZ, He RR. An automatic system controlled by computer for carotid sinus perfusion. Chin J Appl Physiol,1993, 9: 156-159
15 Kraske S, Cunningham JT, Hajduczok G, et al. Mechanosensitive ion channels in putative aortic baroreceptor neurons. Am J Physiol, 1998, 275: 1497-1501
16 Chapleau MW, Abboud FM. Modulation of baroreceptor activity by ionic and paracrine mechanisms: an overview. Braz J Med Biol Res, 1994, 27:1001-1015
17 Xue HM, Wu YM, Xiao L, et al. Effect of resveratrol on baroreceptor activity of carotid sinus in anesthetized male rats. Acta Pharm Sin, 2004, 56: 25-30
18 Schild JH, Clark JW, Hay M, et al. A- and C-type rat nodose sensory neurons: model interpretations of dynamic discharge characteristics. J Neurophysiol, 1994, 71: 2338-2358
19 Matsuda T, Bates JN, Lewis SJ, et al. Modulation of baroreceptor activity by nitric oxide and S-nitrosocysteine. Circ Res, 1995, 76: 426-433
20 Robert M, Matthew N. Cardiovascular Physiology. 1th ed. Beijing: Health Science Asia, Elsevier Science, 2002: 190-196
1 Jos Kleijnen, Paul Knipschild. Ginkgo biloba. Lancet, 1992, 340: 1136-1139
2 Xia SH, Fang DC. Pharmacological action and mechanisms of ginkgolide B. Chin Med J, 2007, 120: 922-928
3 Lopes-Martins R, Catelli M, Araújo C, et al. Pharmacological evidence of a role for platelet activating factor as a modulator of vasomotor tone and blood pressure. Eur J Pharmacol, 1996, 308: 287-294
4 Marrache AM, Gobeil F Jr, Bernier SG, et al. Proinflammatory gene induction by platelet-activating factor mediated via its cognate nuclear receptor. J Immunol, 2002, 169: 6474-6481
5 Giuseppe Montrucchio, Giuseppe Alloatti, Giovanni Camussi. Role of platelet-ativating factor in cardiovascular pathophysiology. Physiol Rev, 2000, 80: 287-294
6 Hosford D, Braquet P. Antagonists of Platelet-Activating Factor: Chemistry, Pharmacology and Clinical Applications. Prog Med Chem, 1990, 27: 325-380
7 Dhainaut JF, Tenaillon A, Hemmer M, et al. Confirmatory platelet-activating factor receptor antagonist trial in patients with severe gram-negative bacterial sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. BN 52021 Sepsis Investigator Group. Crit Care Med, 1998, 26: 1963-1971
8 Nishida S, Satoh H. Comparative vasodilating actions among terpenoids and flavonoids contained in Ginkgo biloba extract. Clin Chim Acta, 2004, 339: 129-133
9 Satoh H, Nishida S. Electropharmacological actions of Ginkgo biloba extract on vascular smooth and heart muscles. Clin Chim Acta, 2004, 342: 13-22
10 Yang Hui, Xu Yongjian, Zhang Zhenxiang. The effect of ginkgo biloba on hypoxic pulmonary hypertension and the role of protein kinase C. Chin J of Tuberc Respir Dis, 2000, 23: 602-605
11 Ji Ningdong, Wei Enhuei, Cheng Qi. Effects of ginkgolides on cell proliferation induced by angiotensinⅡin cultured calf vascular smooth muscle cells. Jiangsu Med J, 2001, 27: 747-748
12 Liebgott T, Miollan M, Berchadsky Y, et al. Complementary cardioprotective effects of flavonoid metabolites and terpenoid constituents of Ginkgo biloba extract (EGb 761) during ischemia and reperfusion. Basic Res Cardiol, 2000, 95: 368-377
13 Pietri S, Maurelli E, Drieu K, et al. Cardioprotective and anti-oxidant effects of the terpenoid constituents of Ginkgo biloba extract (EGb 761). J Mol Cell Cardiol, 1997, 29: 33-42
14 Zhang Zhixiong, Qi Xiaoyan, Xu Youqiu. Effect of ginkgolide B on L-type calcium current and cytosolic [Ca2+]i in guinea pig ischemic ventricular myocytes. Acta Physiol Sin, 2003, 55: 24-28
15 Zhang Genbao, Chen Dongyun, Gui Cangqing. Experimental study on protective effect of ginkgolide B on isolated rats' hearts with ischemia-reperfusion. Chin J of Trad Med Sci and Tech, 2005, 12: 92-94
16 Gao Jian, Wang Qiujuan, Tang Yu, et al. Effect of ginkgolides on myocardial ischemic injury induced by isoprenaline. Tradi Chin Drug Res & Clin Pharma, 2004,
15: 151-155
17 Moore JM, Earnest MA, DiSimone AG, et al. A PAF receptor antagonist, BN 52021, attenuates thromboxane release and improves survival in lethal canine endotoxemia. Circ Shock, 1991, 35: 53-59
18 Cheng D, Chen W. Effects of ginkgolide B on isobarichypoxic pulmonary hypertension in rats. Chin Med J, 1996, 109: 881-884
19 Li DZ, Sharma R, Zeng QT. Effects of Ginkgo leaf extract on function of dendritic cells and Th1/Th2 cytokines in patients with unstable angina pectoris. Chin J Integr Med, 2005, 11: 260-263
20 Nemcsik J, Kordás K, Egresits J, et al. Synergistic interaction of endogenous platelet-activating factor and vasopressin in generating angina in rats. Eur J Pharmacol, 2004, 13: 195-202
21 Chopra K, Singh M, Gupta S, et al. Involvement of oxygen free radicals in the action of BN 52021 (PAF antagonist) to limit myocardial infarct size. Methods Find Exp Clin Pharmacol, 1993, 15: 437-445
22 Chakrabarty S, Thomas P, Sheridan DJ. Contribution of platelets and platelet-activating factor (PAF) to the arrhythmogenic, haemodynamic and necrotic effects of acute myocardial ischaemia. Eur Heart J, 1991, 12: 583-589
23 Maruyama M, Farber NE, Vercellotti GM, et al. Evidence for a role of platelet activating factor in the pathogenesis of irreversible but not reversible myocardial injury after reperfusion in dogs. Am Heart J, 1990, 120: 510-520
24 Qi Xiaoyan, Zhang Zhixiong, Cui Qiqi, et al. The effect of ginkgolide B on action potential, L-type calcium current and delayed rectifier potassium current in ischemic guineapig ventricular myocytes. Chin J Appl Physiol, 2004, 20: 24-28
25 Yang LZ, Zhang Y, Li JX, et al. Effects of BN-52021 on AP and L-type calcium channel in guinea pig’s ventricular myocytes. Chin Pharmaco Bull, 2002, 16: 195-198