Clozel J P, Fischli W, Ménard J
F. Hoffmann-La Roche Ltd, Basel, Switzerland.
J Hypertens. 1993 Jan;11(1):75-81. doi: 10.1097/00004872-199301000-00011.
To compare the acute hypotensive effects of three different methods of inhibiting the renin-angiotensin system in a primate model of cyclosporin-induced hypertension.
The effects of maximally effective doses of an angiotensin I converting enzyme inhibitor, antihuman renin antibodies or a renin inhibitor (Ro 42-5892) on arterial pressure were evaluated in cyclosporin-treated monkeys.
Squirrel monkeys were made hypertensive by a 4-week treatment with oral cyclosporin (30 mg/kg) and were equipped with a telemetry system in order to measure arterial blood pressure in the conscious state.
Each inhibitor induced a complete suppression of plasma angiotensin II 1 h after administration. The renin antibodies did not decrease blood pressure. Cilazapril decreased blood pressure and Ro 42-5892 was more effective than cilazapril. Moreover, when the renin inhibitor was administered after injection of renin antibodies (rabbit antiserum, 0.4 ml intravenously) or after cilazapril (10 mg/kg orally), it induced a supplementary fall in blood pressure.
These data demonstrate that in this experimental model of hypertension the three different methods of maximal inhibition of the renin-angiotensin system do not lead acutely to the same blood pressure decrease. The results also suggest that renin inhibition might be more effective than angiotensin converting enzyme inhibition in certain forms of hypertension.
在环孢素诱导的高血压灵长类动物模型中，比较三种不同抑制肾素-血管紧张素系统方法的急性降压效果。
在环孢素处理的猴子中评估血管紧张素I转换酶抑制剂、抗人肾素抗体或肾素抑制剂（Ro 42-5892）最大有效剂量对动脉压的影响。
松鼠猴经口服环孢素（30mg/kg）4周处理后制成高血压模型，并配备遥测系统以测量清醒状态下的动脉血压。
给药1小时后，每种抑制剂均能完全抑制血浆血管紧张素II。肾素抗体未降低血压。西拉普利降低了血压，Ro 42-5892比西拉普利更有效。此外，在注射肾素抗体（兔抗血清，静脉注射0.4ml）或西拉普利（口服10mg/kg）后给予肾素抑制剂，可导致血压进一步下降。
这些数据表明，在该高血压实验模型中，三种不同的最大程度抑制肾素-血管紧张素系统的方法不会急性导致相同程度的血压下降。结果还表明，在某些形式的高血压中，肾素抑制可能比血管紧张素转换酶抑制更有效。
