BQ-123是一种选择性内皮素A受体拮抗剂，可降低不同高血压大鼠模型的血压。

BQ-123, a selective endothelin subtype A-receptor antagonist, lowers blood pressure in different rat models of hypertension.

作者信息

Douglas S A, Gellai M, Ezekiel M, Ohlstein E H

机构信息

Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.

出版信息

J Hypertens. 1994 May;12(5):561-7.

PMID:7930556

Abstract

OBJECTIVE

To investigate the role of endothelin-1 in the pathogenesis of hypertension directly by using the selective endothelin subtype A-receptor antagonist BQ-123.

METHODS

The antihypertensive and hemodynamic effects of sustained BQ-123 administration were examined in conscious, unrestrained spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) rats and renin hypertensive rats.

RESULTS

Sustained infusions of BQ-123 (0.16-164 nmol/kg per min, intravenously, for 6 h) produced dose-dependent reductions in mean arterial pressure in SHR, the maximal reduction being obtained with a dose of 16 nmol/kg per min. This reversible response was evident up to 14 h after the cessation of antagonist infusion. The antihypertensive response to a maximal dose of BQ-123 was associated with bradycardia, but only a minimal reduction in cardiac output (since the stroke volume was elevated) in the SHR. Therefore, the antihypertensive effect of BQ-123 resulted from a decrease in total peripheral resistance. In contrast, in WKY rats the infusion of the high dose (164 nmol/kg per min, intravenously for 6 h) produced a small but significant reduction in mean arterial pressure. BQ-123 did not alter the pressor response or tachycardia observed in pithed SHR following stimulation of the thoracolumbar sympathetic outflow. BQ-123 was also antihypertensive in renin hypertensive rats, lowering the blood pressure to an extent similar to that observed in SHR.

CONCLUSION

The data presented indicate a role for endothelin in the pathophysiology of hypertension.

摘要

目的

通过使用选择性内皮素 A 型受体拮抗剂 BQ - 123 直接研究内皮素 - 1 在高血压发病机制中的作用。

方法

在清醒、未束缚的自发性高血压大鼠（SHR）、正常血压的 Wistar - Kyoto（WKY）大鼠和肾素性高血压大鼠中检测持续给予 BQ - 123 的降压和血流动力学效应。

结果

持续输注 BQ - 123（0.16 - 164 nmol/kg 每分钟，静脉注射，持续 6 小时）使 SHR 的平均动脉压呈剂量依赖性降低，最大降幅在剂量为 16 nmol/kg 每分钟时获得。这种可逆反应在拮抗剂输注停止后长达 14 小时仍很明显。对最大剂量 BQ - 123 的降压反应与心动过缓相关，但在 SHR 中心输出量仅略有降低（因为每搏输出量升高）。因此，BQ - 123 的降压作用源于总外周阻力的降低。相比之下，在 WKY 大鼠中输注高剂量（164 nmol/kg 每分钟，静脉注射 6 小时）使平均动脉压有小幅但显著的降低。BQ - 123 并未改变刺激胸腰段交感神经传出纤维后在去脑 SHR 中观察到的升压反应或心动过速。BQ - 123 在肾素性高血压大鼠中也具有降压作用，将血压降低到与 SHR 中观察到的程度相似。