ROLE OF BRADYKININ IN MEDIATING VASCULAR EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITORS IN HUMANS

Background The angiotensin-converting enzyme (ACE) not only generates angiotensin Il but is also the main enzyme that destroys bradykinin. I t has been hypothesized, therefore, that bradykinin is involved in the vascular effects of ACE inhibitors. However, its contribution has nev er been demonstrated in humans because of the lack of specific bradyki nin receptor antagonists. Methods and Results High-resolution ultrasou nd and Doppler were used to measure radial artery diameter and blood f low in 10 healthy volunteers. The vascular effects of the ACE inhibito r quinaprilat, the selective bradykinin B-2-receptor antagonist icatib ant, and their combination were determined at rest, during reactive hy peremia (with increased flow causing endothelium-mediated, flow-depend ent dilation), and during sodium nitro-prusside, causing endothelium-i ndependent dilation. Neither icatibant nor quinaprilat affected arteri al diameter or blood flow at rest. However, icatibant reduced flow-dep endent dilation by 33%, and quinaprilat increased flow-dependent dilat ion over baseline by 46%. After coinfusion of quinaprilat and icatiban t, flow-dependent dilation was reduced to a similar extent as after in fusion of icatibant alone. Conclusions ACE inhibition enhances flow-de pendent, endothelium-mediated dilation in humans by a bradykinin-depen dent mechanism. This observation indicates that accumulation of endoge nous bradykinin is involved in the vascular effects of ACE inhibitors in humans.