De Meyer G R, Bult H, Herman A G
Division of Pharmacology, University of Antwerp (UIA), Wilrijk, Belgium.
J Cardiovasc Pharmacol. 1992;20 Suppl 12:S205-7. doi: 10.1097/00005344-199204002-00058.
During neointima formation, which is an early and essential step in the development of atherosclerosis, endothelium-independent relaxations (nitroglycerin, 3-morpholinosydnonimine) are preserved, whereas muscarinic endothelium-dependent relaxation becomes impaired. The present study was undertaken to determine the selectivity of this impairment. The neointima was induced by positioning a nonocclusive, soft silicone collar around the left carotid artery of rabbits. The contralateral artery served as a control. Seven days later, vascular rings were mounted in organ chambers, contracted with phenylephrine (0.35 microM), and cumulative dose-relaxation curves were made. Intima-bearing vessels were less sensitive to acetylcholine, confirming the original observation. In contrast, the dose-relaxation curves for substance P and for the calcium ionophore A23187 were not altered in the presence of neointima. The curve for ATP was even shifted to the left. These results suggest that the nitric oxide synthase: cyclic GMP system remains intact in intima-bearing vessels and that the diminished endothelium-dependent relaxations are due to a selective alteration of the muscarinic receptors.
在新生内膜形成过程中，这是动脉粥样硬化发展的早期且关键步骤，非内皮依赖性舒张（硝酸甘油、3 - 吗啉代 sydnonimine）得以保留，而毒蕈碱型内皮依赖性舒张则受损。本研究旨在确定这种损伤的选择性。通过在兔左颈动脉周围放置一个非闭塞性软硅胶环诱导新生内膜形成。对侧动脉作为对照。7天后，将血管环安装在器官浴槽中，用去氧肾上腺素（0.35微摩尔）收缩，绘制累积剂量 - 舒张曲线。有内膜的血管对乙酰胆碱的敏感性较低，证实了最初的观察结果。相比之下，在有新生内膜的情况下，P物质和钙离子载体A23187的剂量 - 舒张曲线未改变。ATP的曲线甚至向左移动。这些结果表明，一氧化氮合酶：环鸟苷酸系统在有内膜的血管中保持完整，内皮依赖性舒张减弱是由于毒蕈碱受体的选择性改变。
