Endothelin-1 is an endothelium-derived peptide with powerful vasoconstrictor activity. Previous studies in the forearm circulation of normal volunteers have suggested that endogenous endothelin is physiologically important in regulating basal vascular tone. The endothelin system has been implicated in the pathophysiology of heart failure and hypertension. There is increasing evidence that circulating and tissue levels of endothelin are elevated in patients with coronary artery disease suggesting that endothelin may also be involved in the pathophysiology of atherosclerosis. Atherosclerosis is associated with abnormal endothelial and vasomotor function, but it is not known whether the increase in endothelin activity is functionally important in these phenomena. Furthermore, the majority of endothelin released from blood vessels is abluminal, and thus plasma levels are a poor reflection of tissue activity. Recent development of endothelin receptor antagonists has made it possible to investigate endogenous endothelin activity. In this study, we will investigate whether 1) endogenous coronary endothelin activity is increased, 2) it contributes to abnormal metabolic coronary vasodilation, and 3) endothelial dysfunction improves in patients with atherosclerosis or its risk factors after endothelin receptor type A blockade with BQ-123. - Endothelin, endothelial function, atherosclerosis, acetylcholine, BQ123, - Human Subjects
