Antihypertensive activity in rats for SQ 14,225, an orally active inhibitor of angiotensin I-converting enzyme.
Antihypertensive activity in rats for SQ 14,225, an orally active inhibitor of angiotensin I-converting enzyme.
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发表时间：
1978-02
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通讯作者：
R. Laffan;M. E. Goldberg;J. High;T. Schaeffer;M. Waugh;B. Rubin
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作者：
R. Laffan;M. E. Goldberg;J. High;T. Schaeffer;M. Waugh;B. Rubin
SQ 14，225（D-3-巯基-2-甲基丙酰基-L-脯氨酸）显著降低了肾素依赖性肾上腺素结扎和两肾Goldblatt高血压大鼠的血压，但不能降低单肾Goldblatt高血压大鼠的血压。在双肾Goldblatt大鼠中，SQ 14，225（p.o.）是替普罗肽（九肽SQ 20，881（s.c.））的效力的约10倍。SQ 14，225的口服剂量适度降低了Wistar-Kyoto自发性高血压大鼠的血压，但对血压正常的Wistar-Kyoto大鼠没有降低。双侧肾切除术取消了SQ 14，225在自发性高血压大鼠中的抗高血压活性。SQ 14，225和SQ 20，881在双肾肾性高血压大鼠中引起平行的剂量-反应曲线。后处理的自发性高血压大鼠与任何一种药物未能增加有效剂量的其他药物产生的抗高血压作用。结果表明，SQ 14，225主要通过抑制肾素-血管紧张素系统来降低升高的血压，特别是在假定的肾素依赖性高血压模型中。
SQ 14,225 (D-3-mercapto-2-methylpropanoyl-L-proline) markedly lowered the blood pressure of the renin-dependent aortic-ligated and two-kidney Goldblatt hypertensive rat and failed to reduce blood pressure in the one-kidney Goldblatt hypertensive rat. In the two-kidney Goldblatt rat, SQ 14,225 (p.o.) was about 10 times as potent as teprotide, the nonapeptide SQ 20,881 (s.c.). Oral doses of SQ 14,225 moderately reduced the blood pressure of the Wistar-Kyoto spontaneously hypertensive rat but not that of the normotensive Wistar-Kyoto rat. Bilateral nephrectomy abolished the antihypertensive activity of SQ 14,225 in the spontaneously hypertensive rat. SQ 14,225 and SQ 20,881 elicited parallel dose-response curves in the two-kidney renal hypertensive rat. Post-treatment of spontaneously hypertensive rats with either agent failed to augment the antihypertensive effect produced by effective doses of the other agent. The results suggest that SQ 14,225 acts primarily by inhibiting the renin-angiotensin system to reduce elevated blood pressure, especially in presumably renin-dependent models of hypertension.