Effects of chronic infusion of renin inhibitor A-64662 in sodium-depleted monkeys.
Effects of chronic infusion of renin inhibitor A-64662 in sodium-depleted monkeys.
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长期输注肾素抑制剂 A-64662 对缺钠猴的影响。
DOI：
10.1161/01.hyp.13.3.262
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Wilkes,BM
中科院分区：
文献类型：
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作者：
Verburg,KM;Kleinert,HD;Kadam,JR;Chekal,MA;Mento,PF;Wilkes,BM
对钠耗尽的食蟹猴静脉注射有效的灵长类选择性肾素抑制剂 A-64662 (n = 8) 或载体 (n = 6) 7 天，以研究对动脉压、钠排泄和肾素-血管紧张素-醛固酮系统的慢性影响。 0.1-mg/kg 静脉注射推注后连续输注 A-64662 0.01 mg/kg/min，给药 1 天后平均动脉压从 89 +/- 3（4 个对照天的平均值）降低至 75 +/- 4 mm Hg（p 小于 0.05）。这种减少与血浆肾素活性 (PRA) 显着抑制相关，从 57.7 +/- 11.1 降至 1.3 +/- 0.6 ng 血管紧张素 I (Ang I)/ml/hr（p 小于 0.05）。在 A-64662 输注第 2-7 天观察到类似的低血压水平（范围 73 +/- 4 至 77 +/- 4 mm Hg），PRA 仍受到抑制，范围为 0.6 +/- 0.4 至 1.9 +/- 1.0 ng Ang I/ml/hr。在 A-64662 输注的第二天和第七天，血浆血管紧张素 II (Ang II) 水平从对照值 66.7 +/- 20.2 分别降低至 12.4 +/- 3.3 和 26.4 +/- 6.5 pg/ml（p 小于 0.05）。相比之下，单独输注载体对平均动脉压、PRA 或血浆 Ang II 浓度没有明显影响。在 A-64662 输注的第二天和第三天，血浆醛固酮较对照组下降（p 小于 0.05），但在整个研究过程中未检测到治疗组之间的差异。在 A-64662 输注过程中，尿钠排泄量保持在控制水平。停止 A-64662 给药导致平均动脉压在 1 天内恢复至输注前水平。这项研究表明，连续输注 A-64662 会导致缺钠猴出现持续低血压。这种效应似乎至少部分与抑制 PRA 和降低血浆 Ang II 水平有关。
The potent and primate-selective renin inhibitor A-64662 (n = 8) or vehicle (n = 6) was administered intravenously for 7 days to sodium-depleted cynomolgus monkeys to investigate the chronic effects on arterial pressure, sodium excretion, and the renin-angiotensin-aldosterone system. A 0.1-mg/kg i.v. bolus followed by a continuous 0.01-mg/kg/min infusion of A-64662 lowered mean arterial pressure from 89 +/- 3 (average of 4 control days) to 75 +/- 4 mm Hg (p less than 0.05) after 1 day of administration. This decrement was associated with marked inhibition of plasma renin activity (PRA) from 57.7 +/- 11.1 to 1.3 +/- 0.6 ng angiotensin I (Ang I)/ml/hr (p less than 0.05). Similar hypotensive levels (range 73 +/- 4 to 77 +/- 4 mm Hg) were observed on days 2-7 of A-64662 infusion and PRA remained suppressed, ranging from 0.6 +/- 0.4 to 1.9 +/- 1.0 ng Ang I/ml/hr. Plasma angiotensin II (Ang II) levels were reduced (p less than 0.05) from the control value of 66.7 +/- 20.2 to 12.4 +/- 3.3 and 26.4 +/- 6.5 pg/ml on the second and seventh days, respectively, of A-64662 infusion. In contrast, infusion of vehicle alone had no discernible effect on mean arterial pressure, PRA, or plasma Ang II concentrations. Plasma aldosterone decreased (p less than 0.05) from control on the second and third days of A-64662 infusion, although differences between the treatment groups were not detected throughout the study. Urinary sodium excretion remained at control levels throughout the infusion of A-64662. Cessation of A-64662 administration resulted in a recovery of mean arterial pressure to preinfusion levels within 1 day. This study indicates that continuous infusion of A-64662 results in a sustained hypotension in sodium-depleted monkeys. This effect appears to be related, at least partially, to inhibition of PRA and lower plasma Ang II levels.