Husain S, Andrews N P, Mulcahy D, Panza J A, Quyyumi A A
Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Md 20892-1650, USA.
Circulation. 1998 Mar 3;97(8):716-20. doi: 10.1161/01.cir.97.8.716.
The beneficial effects of aspirin in atherosclerosis are generally attributed to its antiplatelet activities, but its influence on endothelial function remains uncertain. We hypothesized that a cyclooxygenase-dependent constricting factor contributes to the endothelial dysfunction in atherosclerosis and that its action can be reversed by aspirin.
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. Drugs were infused into the femoral artery, and Doppler flow velocity was measured. Acetylcholine-induced but not 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 in 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 versa. The presence of atherosclerosis was an independent determinant of improvement with aspirin. Aspirin had no effect on the responses to either substance P or sodium nitroprusside.
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.
阿司匹林在动脉粥样硬化中的有益作用通常归因于其抗血小板活性，但其对内皮功能的影响仍不确定。我们推测环氧化酶依赖性收缩因子促成了动脉粥样硬化中的内皮功能障碍，且阿司匹林可逆转其作用。
在14例冠状动脉粥样硬化患者和5例有危险因素的患者中，我们在静脉注射阿司匹林前后，用乙酰胆碱和P物质检测股血管内皮功能，用硝普钠检测非内皮依赖性功能。将药物注入股动脉，并测量多普勒流速。动脉粥样硬化患者中，乙酰胆碱诱导的血管舒张降低，但P物质或硝普钠诱导的血管舒张未降低，有危险因素的患者则不然。阿司匹林在基线时无作用，但仅改善了动脉粥样硬化患者中乙酰胆碱介导的血管舒张；在峰值剂量时，乙酰胆碱介导的股血管阻力指数降低了19±5%，P = 0.002。乙酰胆碱的基线反应与阿司匹林改善程度之间存在相关性（r = 0.5，P = 0.05）。因此，对乙酰胆碱反应低下的患者使用阿司匹林后改善更大，反之亦然。动脉粥样硬化的存在是阿司匹林改善效果的独立决定因素。阿司匹林对P物质或硝普钠的反应均无影响。
环氧化酶依赖性、内皮源性血管收缩因子释放调节动脉粥样硬化患者中乙酰胆碱诱导的外周血管舒张。阿司匹林改善内皮功能障碍可能会改善血管舒张、减少血栓形成并抑制动脉粥样硬化进展，为阿司匹林在动脉粥样硬化中的有益作用提供了病理生理学基础。
