Hornig B, Kohler C, Drexler H
Abteilung Kardiologie, Medizinische Hochschule Hannover, Germany.
Circulation. 1997 Mar 4;95(5):1115-8. doi: 10.1161/01.cir.95.5.1115.
The angiotensin-converting enzyme (ACE) not only generates angiotensin II but is also the main enzyme that destroys bradykinin. It has been hypothesized, therefore, that bradykinin is involved in the vascular effects of ACE inhibitors. However, its contribution has never been demonstrated in humans because of the lack of specific bradykinin receptor antagonists.
High-resolution ultrasound and Doppler were used to measure radial artery diameter and blood flow in 10 healthy volunteers. The vascular effects of the ACE inhibitor quinaprilat, the selective bradykinin B2-receptor antagonist icatibant, and their combination were determined at rest, during reactive hyperemia (with increased flow causing endothelium-mediated, flow-dependent dilation), and during sodium nitroprusside, causing endothelium-independent dilation. Neither icatibant nor quinaprilat affected arterial diameter or blood flow at rest. However, icatibant reduced flow-dependent dilation by 33%, and quinaprilat increased flow-dependent dilation over baseline by 46%. After coinfusion of quinaprilat and icatibant, flow-dependent dilation was reduced to a similar extent as after infusion of icatibant alone.
ACE inhibition enhances flow-dependent, endothelium-mediated dilation in humans by a bradykinin-dependent mechanism. This observation indicates that accumulation of endogenous bradykinin is involved in the vascular effects of ACE inhibitors in humans.
血管紧张素转换酶（ACE）不仅能生成血管紧张素II，还是破坏缓激肽的主要酶。因此，有人推测缓激肽参与了ACE抑制剂的血管效应。然而，由于缺乏特异性缓激肽受体拮抗剂，其作用从未在人体中得到证实。
采用高分辨率超声和多普勒技术测量10名健康志愿者的桡动脉直径和血流量。在静息状态、反应性充血期间（血流量增加导致内皮介导的流量依赖性扩张）以及硝普钠给药期间（导致非内皮依赖性扩张），测定ACE抑制剂喹那普利拉、选择性缓激肽B2受体拮抗剂依替巴肽及其联合用药的血管效应。依替巴肽和喹那普利拉在静息状态下均不影响动脉直径或血流量。然而，依替巴肽使流量依赖性扩张降低了33%，而喹那普利拉使流量依赖性扩张比基线增加了46%。喹那普利拉和依替巴肽联合输注后，流量依赖性扩张降低的程度与单独输注依替巴肽后相似。
ACE抑制通过缓激肽依赖性机制增强人体中流量依赖性、内皮介导的扩张。这一观察结果表明，内源性缓激肽的蓄积参与了ACE抑制剂在人体中的血管效应。
