PARADOXICAL VASOCONSTRICTION INDUCED BY ACETYLCHOLINE IN ATHEROSCLEROTIC CORONARY-ARTERIES
PARADOXICAL VASOCONSTRICTION INDUCED BY ACETYLCHOLINE IN ATHEROSCLEROTIC CORONARY-ARTERIES
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DOI：
10.1056/nejm198610233151702
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发表时间：
1986-10-23
影响因子：
158.5
通讯作者：
GANZ, P
中科院分区：
文献类型：
--
作者：
LUDMER, PL;SELWYN, AP;GANZ, P
乙酰胆碱被认为通过促进内皮细胞释放血管松弛物质（内皮源性松弛因子）来扩张正常血管。相反，如果实验性地去除内皮，乙酰胆碱会收缩血管。我们检验了毒蕈碱胆碱能血管舒张在冠状动脉粥样硬化中受损的假设。将不同浓度的乙酰胆碱和非内皮依赖性血管扩张剂硝酸甘油输注到8例晚期冠状动脉狭窄（狭窄50%）患者、4例冠状动脉造影正常患者和6例轻度冠状动脉粥样硬化（狭窄20%）患者的左前降支中进行比较。通过定量血管造影评估血管反应。在四条正常冠状动脉的几个节段中，乙酰胆碱引起了从1.94 +-的控制直径的剂量依赖性扩张。0.16毫米至2.16毫米。最大乙酰胆碱剂量为0.15 mm （P < 0.01）。相比之下，所有8条晚期狭窄的动脉都表现出剂量依赖性收缩，从1.05 .+-。0.05 ~ 0.32 .+。0.16 mm时乙酰胆碱浓度最高（P < 0.01），暂时性闭塞5例。6个最小病变的血管中有5个也因乙酰胆碱而收缩。然而，所有血管对硝酸甘油的反应都是扩张。我们得出结论，乙酰胆碱诱导的矛盾血管收缩发生在冠状动脉粥样硬化的早期和晚期。我们的初步研究结果表明，血管对乙酰胆碱的异常反应可能代表了内皮血管舒张功能的缺陷，并且可能在冠状动脉痉挛的发病机制中起重要作用。
Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (> 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (< 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 .+-. 0.16 mm to 2.16 .+-. 0.15 mm with the maximal acetylcholine dose (P < 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 .+-. 0.05 to 0.32 .+-. 0.16 mm at the highest concentration of acetylcholine (P < 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.