ENDOTHELIAL CONTROL OF LARGE CORONARY ARTERY VASOACTIVI

这项研究旨在阐明血管控制的机制。 这解释了与冠状动脉相关的异常血管活动 疾病。对血管内皮细胞的损伤，高血清胆固醇， 动脉粥样硬化和血流速度的变化是 改变血管的反应性。然而，很少有系统的研究。 研究了导致这种血管活性改变的机制。 此外，以前大多数关于内皮细胞作用的工作 在血管控制中升高的胆固醇水平已经在 隔离的血管或麻醉的动物，因此可能不会 表明了完好无损的清醒动物的控制机制。这 研究提案将系统地评估以下变化的影响 (1)冠脉血流，(2)去除内皮，(3)急性和(4) 慢性膳食升高对血清胆固醇和血浆脂蛋白的影响 清醒犬冠状动脉大直径的控制。 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神经血管收缩和扩张，以及 参与这些机制的受体亚型。我们还将检查 内皮剥离与急、慢性胆固醇的关系 冠脉管壁弹性特性的高程。地区性 将对心肌功能进行评估，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。这项提议的中心假设是，取消 冠状动脉内皮细胞，或血浆胆固醇水平升高， 会降低对自主神经血管扩张剂刺激的反应，同时增强 对自主神经血管收缩刺激的反应。累积效应 这些改变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的。对机制的澄清 负责改变的血管活动将产生基本的知识 大型冠状动脉控制机制，并最终提供了洞察力 冠脉痉挛的发病机制。

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.