Role of Endogenous Bradykinin in Human Coronary Vasomotor Control

Abstract

Background Bradykinin is a potent vasodilator that acts through B 2 kinin receptors to stimulate the release of endothelium-derived nitric oxide, prostacyclin, and hyperpolarizing factor. In this study, we investigated the contribution of endogenous bradykinin to vasomotor control in the human coronary circulation. Methods and Results The selective bradykinin B 2 receptor antagonist HOE 140 was infused into the left main coronary artery (200 μg/min for 15 minutes) in 15 patients without significant coronary stenoses. Epicardial responses were evaluated by quantitative coronary blood flow with a Doppler flow-velocity wire. Flow-dependent dilation (n=10; intracoronary papaverine) and acetylcholine responses (n=5) were assessed before and after HOE 140. After HOE 140, there was a reduction in luminal area in the proximal ( P <.001), mid ( P <.001), and distal ( P <.05) coronary arteries. HOE 140 led to an increase in coronary vascular resistance ( P <.001) and a decrease in coronary blood flow ( P <.001). After bradykinin B 2 receptor blockade, there was a reduction in flow-dependent dilation (23.4±6.9% to 3.9±6.0%, P <.001), the extent of which correlated with the degree of basal vasoconstriction after HOE 140 in the same vessel segment ( P <.05). Acetylcholine responses were unchanged after HOE 140. Conclusions The results of this study demonstrate for the first time a role for endogenous bradykinin in mediating normal vasomotor responses in resistance and epicardial coronary vessels under basal and flow-stimulated conditions in the human coronary circulation.