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盐平衡对贝那普利在正常男性体内的肾脏及血流动力学作用的影响。

Effect of salt balance on the renal and hemodynamic actions of benazepril in normal men.

作者信息

Noormohamed F H, Fuller G N, Lant A F

机构信息

Department of Clinical Pharmacology and Therapeutics, Charing Cross and Westminster Medical School, Westminster Hospital, London, U.K.

出版信息

J Clin Pharmacol. 1989 Oct;29(10):928-37. doi: 10.1002/j.1552-4604.1989.tb03257.x.

Abstract

Renal and hemodynamic effects of diet alone and of single oral doses of the nonsulphydryl angiotensin converting enzyme (ACE) inhibitor, benazepril (10 mg), were investigated in eight healthy volunteers under stable conditions of high salt intake (300 mmol NaCl/day) and low salt intake (10 mmol NaCl/day), in a double blind, placebo controlled study. There were no changes in blood pressure between the two dietary extremes either during the run-in period or once sodium balance had been achieved. Mean renal plasma flow was higher, by approximately 10% and renal vascular resistance lower by 15%, on high salt diet compared to low salt diet. Glomerular filtration rates were found to be similar irrespective of the state of salt balance. Both plasma urate concentration and plasma renin activity were significantly elevated in the low salt compared to high salt state. Benazepril caused a greater fall in blood pressure in the sodium depleted state. Significant increases in the mean renal plasma flow, in the order of 15-20%, were seen over 6 h postbenazepril when compared with placebo response, regardless of the level of salt intake. Glomerular filtration rate over the same period remained unaltered. Benazepril doubled the urinary excretion of sodium over the first 4 hours after dosing whilst on the low salt diet; the equivalent increase during salt loading was approximately 20%. These results suggest that benazepril may exert direct effects on renal tubular function additional to those achieved through ACE blockade.

摘要

在一项双盲、安慰剂对照研究中,对8名健康志愿者在高盐摄入(300 mmol氯化钠/天)和低盐摄入(10 mmol氯化钠/天)的稳定条件下,单独饮食以及单次口服非巯基血管紧张素转换酶(ACE)抑制剂贝那普利(10 mg)的肾脏和血流动力学效应进行了研究。在导入期或达到钠平衡后,两种极端饮食状态下的血压均无变化。与低盐饮食相比,高盐饮食时平均肾血浆流量约高10%,肾血管阻力低15%。无论盐平衡状态如何,肾小球滤过率均相似。与高盐状态相比,低盐状态下血浆尿酸盐浓度和血浆肾素活性均显著升高。贝那普利在钠缺乏状态下导致更大幅度的血压下降。与安慰剂反应相比,无论盐摄入量如何,服用贝那普利后6小时内平均肾血浆流量显著增加,增幅约为15%-20%。同期肾小球滤过率保持不变。在低盐饮食时,给药后前4小时贝那普利使钠尿排泄量增加一倍;在盐负荷期间,同等增加幅度约为20%。这些结果表明,贝那普利除了通过ACE阻断发挥作用外,可能还对肾小管功能有直接影响。

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