ENDOTHELIAL CONTROL OF LARGE ILIAC ARTERY VASOACTIVITY

本研究旨在阐明血管控制的机制 导致了冠状动脉的异常血管活性 疾病 损伤血管内皮细胞，高血清胆固醇， 动脉粥样硬化和血流速度的变化是 改变血管反应性。 然而，很少有研究系统地 研究了这种血管活性改变的机制。 此外，大多数关于内皮细胞作用的先前工作 和胆固醇水平升高的血管控制已经进行了， 隔离的血管或麻醉的动物，因此， 这表明了完整的有意识的动物的控制机制。 这 研究建议将系统地评估变化的影响， (1)冠状动脉血流量，（2）去除内皮，（3）急性和（4） 血清胆固醇和血浆脂蛋白的慢性饮食升高 控制清醒犬冠状动脉直径增大。 将特别注意这些干预措施对以下方面的影响： 肾上腺素能和胆碱能自主血管收缩和血管舒张，以及 参与这些机制的受体亚型。 我们亦会研究 内皮去除和急性或慢性胆固醇的影响 冠状动脉血管壁的弹性特性升高。 区域 将评估心肌功能，以确定可能的 心肌代谢需求改变对大冠状动脉的影响 口径的 这一建议的核心假设是， 冠状动脉内皮细胞，或升高的血浆胆固醇水平， 将减少对自主血管扩张刺激的反应，同时增强 对自主血管收缩刺激的反应。 的累积影响 这些变化可能解释了更大程度的血管收缩 在血管痉挛发作期间观察到。 澄清机制 导致血管活性改变的原因将产生基础知识 大冠状动脉控制机制，并最终提供见解 冠状动脉痉挛的发病机制

This research is designed to elucidate the mechanisms of vascular control that account for the abnormal vasoactivity associated with coronary artery disease. Damage to vascular endothelial cells, high serum cholesterol, atherosclerosis, and changes in blood flow velocity, are factors which alter vascular reactivity. However, few studies have systematically studied the mechanisms responsible for this altered vasoactivity. Furthermore, most previous work concerning the role of endothelial cells and elevated cholesterol levels in vascular control has been conducted in isolated vessels or anesthetized animals and, therefore, may not be indicative of control mechanisms in the intact, conscious animal. This research proposal will systematically evaluate the effects of changes in (1) coronary blood flow, (2) removal of endothelium, (3) acute and (4) chronic dietary elevation of serum cholesterol and plasma lipoproteins on the control of large coronary artery diameter in the conscious dog. Specific attention will be paid to the effects of these interventions on adrenergic and cholinergic autonomic vasoconstriction and vasodilation, and the receptor subtypes involved in these mechanisms. We will also examine the effects of endothelium removal and acute or chronic cholesterol elevation on the elastic properties of the coronary vessel wall. Regional myocardial function will be assessed in order to determine the possible effects of altered myocardial metabolic demand on large coronary artery caliber. The central hypothesis of this proposal is that removal of coronary artery endothelial cells, or elevated plasma cholesterol levels, will reduce the response to autonomic vasodilator stimuli, while enhancing the response to autonomic vasoconstrictor stimuli. The cumulative effects of these alterations may account for the greater degree of vasoconstriction observed during episodes of vasospasm. Clarification of the mechanisms responsible for the altered vasoactivity will yield fundamental knowledge of large coronary artery control mechanisms, and ultimately provide insight into the pathogenesis of coronary artery spasm.