We tested the hypothesis that acute coronary artery hypertension may damage vascular endothelium and alter vasomotor responses to humoral agents. We examined effects of intracoronary infusion of the endothelium-dependent agent serotonin and two endothelium-independent agents, angiotensin II and methoxamine, on large coronary artery diameter in the blood perfused dog heart. Responses were examined before and 30 minutes after brief periods of coronary hypertension ( Received March 3, 1987; accepted July 9, 1987 dothelial damage ranged from discrete endothelial lesions in pial arterioles 4 and intestinal arterioles 5 to disruption of cellular junctions and increases in vascular permeability in mesenteric vessels 6 and focal areas of endothelial denudation and platelet adherence in mesenteric arterioles. 7 In the cerebral circulation, acute hypertension not only damaged pial artery endothelium but also abolished dilation to acetylcholine and resulted in constriction of pial arteries to acetylcholine. 8 We have previously examined the role of endothelium on responses of large coronary arteries to vasoconstrictors in the intact circulation.9 Mechanical removal of endothelium selectively augmented constriction of coronary arteries to serotonin. The present studies were undertaken to test the hypothesis that acute hypertension results in altered vasomotor responses in the coronary circulation that persist beyond the duration of hypertension. We postulated that altered vasomotor responses are mediated by impaired endothelial function after hypertension. To test this hypothesis, coronary artery pressure was raised from 80 mm Hg to 200 mm Hg for brief periods. We examined responses of coronary arteries to two endothelium-dependent agents, serotonin and acetylcholine, and to two by guest on
