Harrison D G, Freiman P C, Armstrong M L, Marcus M L, Heistad D D
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
Circ Res. 1987 Nov;61(5 Pt 2):II74-80.
We have previously found that vascular relaxation to acetylcholine and thrombin is markedly impaired in vessels from monkeys with diet-induced atherosclerosis. In the present study, we found that both normal and atherosclerotic vessels relaxed completely to the calcium ionophore A23187, which stimulates release of the endothelium-derived relaxing factor by nonreceptor-mediated mechanisms. Atherosclerotic vessels, however, were less sensitive to this agent. The finding that responses to the calcium ionophore were impaired in atherosclerosis suggests that abnormal endothelium-dependent relaxation in atherosclerotic vessels is not related entirely to alterations of thrombin and muscarinic receptors but may also be due to abnormal endothelium-derived relaxing factor production or transfer from the endothelium to the underlying vascular smooth muscle. Neither normal nor atherosclerotic iliac arteries constricted in response to acetylcholine when studied in the nonpreconstricted state. Constriction to acetylcholine in these vessels was not unmasked by removal of the endothelium. Thus, the smooth muscle of iliac vessels from monkeys contains few functioning muscarinic receptors. Impaired relaxation of atherosclerotic vessels to acetylcholine is not due to enhanced muscarinic-mediated constriction or to production of an endothelium-derived constricting factor. In vivo studies were performed to determine if alpha-adrenergic coronary vascular constriction is enhanced in the presence of atherosclerosis. In anesthetized monkeys, myocardial oxygen consumption was increased by two mechanisms, aortic occlusion and phenylephrine infusion. During both aortic occlusion and phenylephrine infusion, decreases in coronary vascular resistance were similar in control and atherosclerotic monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)
我们先前发现，在饮食诱导的动脉粥样硬化猴子的血管中，对乙酰胆碱和凝血酶的血管舒张作用明显受损。在本研究中，我们发现正常血管和动脉粥样硬化血管对钙离子载体A23187均能完全舒张，该载体通过非受体介导机制刺激内皮源性舒张因子的释放。然而，动脉粥样硬化血管对该药物的敏感性较低。动脉粥样硬化中对钙离子载体反应受损的这一发现表明，动脉粥样硬化血管中异常的内皮依赖性舒张并不完全与凝血酶和毒蕈碱受体的改变有关，也可能是由于内皮源性舒张因子产生异常或从内皮转移至其下的血管平滑肌异常所致。在非预收缩状态下研究时，正常和动脉粥样硬化的髂动脉对乙酰胆碱均无收缩反应。去除内皮并不能使这些血管对乙酰胆碱的收缩反应显现出来。因此，猴子髂血管的平滑肌含有很少起作用的毒蕈碱受体。动脉粥样硬化血管对乙酰胆碱舒张受损并非由于毒蕈碱介导的收缩增强或内皮源性收缩因子的产生。进行了体内研究以确定在存在动脉粥样硬化的情况下α-肾上腺素能冠状动脉血管收缩是否增强。在麻醉的猴子中，通过主动脉闭塞和去氧肾上腺素输注这两种机制增加心肌耗氧量。在主动脉闭塞和去氧肾上腺素输注过程中，对照猴子和动脉粥样硬化猴子的冠状动脉血管阻力降低情况相似。（摘要截短至250字）
