PATIENTS WITH EVIDENCE OF CORONARY ENDOTHELIAL DYSFUNCTION AS ASSESSED BY ACETYLCHOLINE INFUSION DEMONSTRATE MARKED INCREASE IN SENSITIVITY TO CONSTRICTOR EFFECTS OF CATECHOLAMINES

Background. Studies in patients undergoing cardiac catheterization have demonstrated that normal coronary arteries dilate and atherosclerotic arteries constrict in response to exercise and the cold pressor test, but the mechanisms are unknown. These vasomotor response are mirrored by the vasomotor response to the endothelium-dependent agent acetylcholine. Exercise and the cold pressor test are associated with adrenergic stimulation and increased circulating catecholamines. The present study tested the hypothesis that coronary arteries with intact endothelial function are relatively resistant to the constrictor effects of catecholamines, whereas arteries with loss of endothelial function have increased sensitivity to catecholamine-induced constriction. Methods and Results. The vasomotor function of the coronary endothelium was assessed by serial acetylcholine infusions (final concentration, 10(-8) to 10(-6) M) in 30 segments in 15 patients with minimal or no evidence of coronary atherosclerosis. The acetylcholine responses were related to the vasomotor response to intracoronary phenylephrine infusion (final concentration, 10(-9) to 10(-6) M) in the same segments. In the group of 18 segments that constricted to acetylcholine, there was a constrictor response to phenylephrine at an approximately 100-fold lower concentration than the group of 12 segments that did not constrict to acetylcholine. Conclusions. These results suggest that the endothelial dysfunction that characterizes early and late atherosclerosis is associated with a marked increase in sensitivity to the constrictor effects of catecholamines. This finding may explain the constrictor responses of atherosclerotic coronary arteries to exercise and the cold pressor test. In stenotic coronary arteries this mechanism may play a role in the production of myocardial ischemia.