Aspirin improves endothelial dysfunction in atherosclerosis

Background-The beneficial effects of aspirin in atherosclerosis are generally attributed to its antiplatelet activities, but its influence on endothelial function remains uncertain. Wie hypothesized that a cyclooxygenase-dependent constricting factor contributes to the endothelial dysfunction in atherosclerosis and that its action call be reversed by aspirin. Methods and Results-In 14 patients with coronary atherosclerosis and 5 with risk factors, we tested femoral vascular endothelial function with acetylcholine and substance P and endothelium-independent function with sodium nitroprusside before and after intravenous aspirin. Drug were infused into the femoral artery, and Doppler flow velocity was measured. Acetylcholine-induced but trot substance P-or sodium nitroprusside-induced vasodilation was lower-in patients with atherosclerosis than in those with only risk factors, Aspirin had no baseline effect but improved acetylcholine-mediated vasodilation only ill patients with atherosclerosis; at the peak dose, acetylcholine-mediated femoral vascular resistance index was 19+/-5%, P=.002 lower, There was a correlation between the baseline response to acetylcholine and the magnitude of improvement with aspirin (r=.5, P=.05). Thus, patients with a depressed response to acetylcholine had greater improvement with aspirin, and vice vena. The presence of atherosclerosis was as an independent determinant of improvement with aspirin. Aspirin had Ilo effect art the responses to either substance P or sodium nitroprusside. Conclusions-Cyclooxygenase-dependent, endothelium-derived vasoconstrictor release modulates acetylcholine-induced peripheral vasodilation in patients with atherosclerosis. Improvement of endothelial dysfunction with aspirin may improve vasodilation, reduce thrombosis, and inhibit progression of atherosclerosis and provides a pathophysiological basis for the beneficial effects of aspirin in atherosclerosis.