Hodsman G P, Brown J J, Cumming A M, Davies D L, East B W, Lever A F, Morton J J, Murray G D, Robertson J I
Am J Med. 1984 Aug 20;77(2A):52-60. doi: 10.1016/s0002-9343(84)80058-3.
The converting enzyme inhibitor enalapril, in single daily doses of 10 to 40 mg, was given to 20 hypertensive patients with renal artery stenosis. The decrease in blood pressure six hours after the first dose of enalapril was significantly related to the pretreatment plasma concentrations of active renin and angiotensin II, and to the concurrent decrease in angiotensin II. Blood pressure decreased further with continued treatment; the long-term decrease was not significantly related to pretreatment plasma renin or angiotensin II levels. At three months, 24 hours after the last dose of enalapril, blood pressure, plasma angiotensin II, and converting enzyme activity remained low, and active renin and angiotensin I high; six hours after dosing, angiotensin II had, however, decreased further. The increase in active renin during long-term treatment was proportionately greater than the increase in angiotensin I; this probably reflects the diminution in renin substrate that occurs with converting enzyme inhibition. Long-term enalapril treatment increased renin secretion by more than 10-fold, and renal venous and peripheral plasma renin concentration by more than 20-fold; however, the mean renal venous renin ratio was not changed. Enalapril caused a reduction in effective renal plasma flow via the affected kidney but a marked and consistent increase on the contralateral side, where renal vascular resistance decreased. The overall increase in effective renal plasma flow was significantly related to the decrease in angiotensin II. Overall glomerular filtration rate was lowered, and serum creatinine and urea increased. Enalapril alone caused a long-term reduction in exchangeable sodium, with slight but distinct increases in serum potassium. In five patients with bilateral renal artery lesions, enalapril given alone for three months did not cause renal function to deteriorate. Enalapril was well tolerated and provided effective long-term control of hypertension; only two of the 20 patients studied required concomitant diuretic treatment.
将每日单次剂量为10至40毫克的转换酶抑制剂依那普利给予20例患有肾动脉狭窄的高血压患者。首次服用依那普利6小时后血压下降与治疗前活性肾素和血管紧张素II的血浆浓度以及同时出现的血管紧张素II下降显著相关。持续治疗后血压进一步下降；长期下降与治疗前血浆肾素或血管紧张素II水平无显著关系。在三个月时，即最后一剂依那普利服用24小时后，血压、血浆血管紧张素II和转换酶活性仍较低，而活性肾素和血管紧张素I较高；然而，给药6小时后，血管紧张素II进一步下降。长期治疗期间活性肾素的增加幅度大于血管紧张素I的增加幅度；这可能反映了转换酶抑制导致的肾素底物减少。长期依那普利治疗使肾素分泌增加超过10倍，肾静脉和外周血浆肾素浓度增加超过20倍；然而，平均肾静脉肾素比值未改变。依那普利通过患侧肾脏导致有效肾血浆流量减少，但对侧肾脏有显著且持续的增加，对侧肾脏血管阻力下降。有效肾血浆流量的总体增加与血管紧张素II的下降显著相关。总体肾小球滤过率降低，血清肌酐和尿素增加。单独使用依那普利可导致可交换钠长期减少，血清钾略有但明显增加。在5例双侧肾动脉病变患者中，单独给予依那普利三个月未导致肾功能恶化。依那普利耐受性良好，可有效长期控制高血压；在研究的20例患者中，只有2例需要同时使用利尿剂治疗。
