Abnormal flow-mediated epicardial vasomotion in human coronary arteries isimproved by angiotensin-converting enzyme inhibition - A potential role ofbradykinin

OBJECTIVES. This study nas performed to determine whether angiotensin conve rting enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation in patients with atherosclerosis or its risk factors and wheth er this is mediated by enhanced bradykinin activity. BACKGROUND. Abnormal coronary vasomotion due to endothelial dysfunction con tributes to myocardial ischemia in patients with atherosclerosis, and its r eversal may have an antiischemic action. Previous studies have shown that A CE inhibition improves coronary endothelial responses to acetylcholine, but whether this is accompanied by improved responses to shear stress remains unknown. METHODS. In 19 patients with mild atherosclerosis, metabolic vasodilation w as assessed during cardiac pacing. Pacing was repeated during separate intr acoronary infusions of low-dose bradykinin (BK) and enalaprilat. Endotheliu m-dependent and -independent vasodilation was estimated with intracoronary BK and sodium nitroprusside respectively. RESULTS. Enalaprilat did not-alter either resting coronary vascular tone or dilation with sodium nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that constricted abnormally with pacing (-5 +/- 1%) dil ated (3 +/- 2%) with pacing in the presence of enalaprilat (p = 0.002). Sim ilarly, BK at a concentration (62.5 ng/min) that did not alter resting diam eter in the constricting segments also improved the abnormal response to a 6 +/- 1% dilation (p < 0.001). Cardiac pacing-induced reduction in coronary vascular resistance of 27 +/- 4% (p < 0.001) remained unchanged after enal aprilat. CONCLUSIONS. Thus ACE inhibition: A) selectively improved endothelium-depen dent but not-independent dilation, and B) abolished abnormal flow-mediated epicardial vasomotion in patients with endothelial dysfunction, in part; by increasing endogenous BK activity. (C) 1999 by the American College of Car diology.