Bossaller C, Habib G B, Yamamoto H, Williams C, Wells S, Henry P D
J Clin Invest. 1987 Jan;79(1):170-4. doi: 10.1172/JCI112779.
The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it.
在从有或没有冠状动脉粥样硬化的心脏移植患者分离出的冠状动脉中，确定了血管舒张对完整内皮的依赖性以及舒张与环磷酸鸟苷（cGMP）积累之间的关系。在非动脉粥样硬化的动脉中，内皮依赖性介质乙酰胆碱产生浓度相关的舒张作用。在动脉粥样硬化的动脉中，乙酰胆碱使内皮依赖性舒张作用消失，P物质和组胺使其部分受到抑制，而离子载体A23187可使其完全保留。在这些动脉中，非内皮依赖性介质硝酸甘油仍然完全有效。动脉粥样硬化条带中环磷酸鸟苷的积累被乙酰胆碱抑制，但A23187和硝酸甘油不会使其减弱。在饮食诱导的动脉粥样硬化兔的主动脉中，同样存在胆碱能舒张功能受损和环磷酸鸟苷积累，而对A23187和硝酸甘油的反应仍然保留。结果表明，动脉粥样硬化动脉中胆碱能反应受损反映的是毒蕈碱缺陷，而非内皮无法释放内皮因子或平滑肌无法对其作出反应。
