Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans

OBJECTIVES The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors. BACKGROUND Although acetylcholine (ACH) is used as a probe for testing vasc ular function in vivo, endogenous bradykinin (BK) regulates resting and flo w-mediated epicardial tone. METHODS In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracor onary ACH (30 mug/min) and BK (62.5 ng/min and 4 mug/min), and endothelium independent function with sodium nitroprusside. Metabolic vasodilation was assessed during cardiac pacing (n = 19). Correlation with serum angiotensin -converting enzyme (ACE) levels and the ACE insertion/deletion genotype was performed. RESULTS There was progressive impairment in AGH-mediated microvascular dila tion with increasing numbers of risk factors (p = 0.025, analysis of varian ce). By contrast, BK- and sodium nitroprusside-mediated microvascular dilat ion was similar in all groups. Similarly, there was no correlation between epicardial coronary responses to ACH and BK; segments that constricted or d ilated with ACH had similar dilator responses with BK. Bradykinin, but not ACH-mediated vasomotion, was depressed in epicardial segments that constric ted with pacing. Finally, epicardial BK responses were depressed in patient s with high ACE levels and in those with the ACE DD genotype. CONCLUSIONS Endothelial dysfunction in atherosclerosis appears to be recept or-specific, involving the muscarinic receptor with relative sparing of the kinin receptor pathways. Abnormal reactivity of epicardial coronary arteri es during physiologic stress is better represented by BK and not by ACH res ponses. Bradykinin activity and, hence, physiologic coronary vasomotion app ears to be influenced by serum ACE levels and the ACE insertion/deletion ge notype. (C) 2000 by the American College of Cardiology.