IMPAIRED MUSCARINIC ENDOTHELIUM-DEPENDENT RELAXATION AND CYCLIC GUANOSINE 5'-MONOPHOSPHATE FORMATION IN ATHEROSCLEROTIC HUMAN CORONARY-ARTERY AND RABBIT AORTA

IMPAIRED MUSCARINIC ENDOTHELIUM-DEPENDENT RELAXATION AND CYCLIC GUANOSINE 5'-MONOPHOSPHATE FORMATION IN ATHEROSCLEROTIC HUMAN CORONARY-ARTERY AND RABBIT AORTA
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DOI:
10.1172/jci112779
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发表时间:
1987-01-01
影响因子:
15.9
通讯作者:
HENRY, PD
HENRY, PD
中科院分区:
医学1区
文献类型:
--
作者:
BOSSALLER, C;HABIB, GB;HENRY, PD

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在从有或没有冠状动脉粥样硬化的心脏移植患者分离的冠状动脉中测定了血管舒​​张对完整内皮的依赖性以及舒张和环鸟苷酸积累之间的关系。在非动脉粥样硬化动脉中,内皮依赖性药物乙酰胆碱产生浓度相关的松弛。在动脉粥样硬化动脉中,乙酰胆碱消除了内皮依赖性松弛,P物质和组胺部分抑制了内皮依赖性松弛,而离子载体A23187则完全保留了内皮依赖性松弛。在这些动脉中,内皮依赖性药物硝酸甘油保持完全活性。乙酰胆碱可抑制动脉粥样硬化条带中环 GMP 的积累,但 A23187 和硝酸甘油则不会减弱环 GMP 的积累。在患有饮食引起的动脉粥样硬化的兔子的主动脉中,在对 A23187 和硝酸甘油保留反应的情况下,同样存在胆碱能松弛和环 GMP 积累受损的情况。结果表明,动脉粥样硬化动脉中胆碱能反应受损反映了毒蕈碱缺陷,而不是内皮细胞无法释放内皮因子或平滑肌对其做出反应。
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.