Sánchez R A, Marcó E, Gilbert H B, Raffaele P, Brito M, Giménez M, Moledo L I
Drugs. 1985;30 Suppl 1:49-58. doi: 10.2165/00003495-198500301-00008.
The purpose of this study was to evaluate the natriuretic effect and renal haemodynamic changes induced by enalapril in patients with essential hypertension. In a group of 11 patients with mild to moderate hypertension with normal renal function, and on a controlled sodium intake (80 mmol/day), a decrease in systolic and diastolic blood pressure was observed (p less than 0.001) after 16 weeks of enalapril treatment (20 mg/day), without a change in heart rate. An increase in plasma renin activity (p less than 0.05) without changes in serum aldosterone, and a decrease in exchangeable sodium (p less than 0.001) were present at the end of the treatment period. In 10 hypertensive patients also taking a dietary sodium of 80 mmol/day, the renal haemodynamics, humoral changes, and urinary sodium excretion were measured during 4 days of enalapril treatment (20 mg/day). There was an increase in urinary sodium excretion on the 3rd and 4th days of treatment (p less than 0.01). The effective renal plasma flow and fractional sodium excretion increased 72 hours after the beginning of treatment (p less than 0.01); the glomerular filtration rate did not change, and filtration fraction decreased at 72 hours. Mean blood pressure fell 2 hours after the first dose (p less than 0.01), and the maximum drop in intrarenal vascular resistance occurred after 72 hours of treatment (p less than 0.01). Plasma renin activity increased (p less than 0.05) and serum aldosterone decreased (p less than 0.01) 2 hours after the first dose. Thereafter, serum aldosterone increased progressively until it reached values similar to those with placebo at 48 and 72 hours of treatment. Urinary kallikrein fell during the 2nd and 3rd day of treatment (p less than 0.01). It was concluded that the decrease in exchangeable sodium was due to a natriuretic effect of enalapril. This effect presumably results from renal haemodynamic changes due to the reduction of angiotensin II. Other mechanisms, such as the reduction of aldosterone and accumulation of kinins, could be contributory factors.
本研究的目的是评估依那普利对原发性高血压患者的利钠作用及肾血流动力学变化。在一组11例轻度至中度高血压且肾功能正常、钠摄入量控制在80 mmol/天的患者中，接受依那普利（20 mg/天）治疗16周后，收缩压和舒张压均下降（p<0.001），心率无变化。治疗期末，血浆肾素活性升高（p<0.05），血清醛固酮无变化，可交换钠减少（p<0.001）。在另外10例同样摄入80 mmol/天膳食钠的高血压患者中，于依那普利（20 mg/天）治疗的4天内测定肾血流动力学、体液变化及尿钠排泄情况。治疗第3天和第4天尿钠排泄增加（p<0.01）。治疗开始72小时后，有效肾血浆流量和钠排泄分数增加（p<0.01）；肾小球滤过率未变，滤过分数在72小时时下降。首剂后2小时平均血压下降（p<0.01），肾内血管阻力最大降幅出现在治疗72小时后（p<0.01）。首剂后2小时血浆肾素活性升高（p<0.05），血清醛固酮下降（p<0.01）。此后血清醛固酮逐渐升高，至治疗48小时和72小时时达到与安慰剂相似的值。治疗第2天和第3天尿激肽释放酶下降（p<0.01）。得出的结论是，可交换钠减少是依那普利利钠作用的结果。这种作用可能是由于血管紧张素II减少导致肾血流动力学变化所致。其他机制，如醛固酮减少和激肽蓄积，可能也是促成因素。
