Case D B, Wallace J M, Keim H J, Weber M A, Drayer J I, White R P, Sealey J E, Laragh J H
Am J Med. 1976 Nov;61(5):790-6. doi: 10.1016/0002-9343(76)90160-1.
This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 addtional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p less than 0.001) and with the pretreatment plasma renin levels (p less than 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but but converting enzyme inhibitor produced changes of greater amplitude (p less than 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade preduced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 +/- 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was -10.2 +/- 1.2 per cent, p less than 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.
本研究旨在更深入地探讨高血压患者对两种阻断肾素 - 血管紧张素系统药物的血压反应差异。因此，39例坐位患者在相同条件下分别接受了血管紧张素II的八肽竞争性拮抗剂沙拉新和九肽转化酶抑制剂SQ20881，后者可阻断血管紧张素I生成血管紧张素II。该研究的第二个部分涉及在另外10项无肾受试者的研究中给予这些药物。虽然两种药物都产生了最大血压反应，且彼此相关性良好（p<0.001），并与治疗前血浆肾素水平相关（p<0.001），但按肾素亚组分析结果显示存在显著差异。因此，两种药物均降低了高肾素水平患者的舒张压，但转化酶抑制剂产生的变化幅度更大（p<0.05）。相反，沙拉新在低肾素水平患者和无肾患者中始终具有升压作用，而转化酶阻断对这些患者的血压无显著影响。在肾素水平正常的组中，对两种药物反应的另一个显著差异是，沙拉新产生中性或升压反应（平均变化为对照舒张压的+2.0±1.5平均标准误（SEM）%），而转化酶抑制剂始终诱导降压反应（平均变化为-10.2±1.2%，p<0.001）。总体而言，结果表明转化酶抑制剂检测依赖血管紧张素II的血压比部分激动剂沙拉新更敏感。此外，两种药物反应的差异不太可能是由于缓激肽蓄积，因为在低肾素水平患者和无肾患者中未观察到对转化酶抑制剂的降压反应。
