ADRENERGIC LIMITATION OF CORONARY FLOW DURING EXERCISE

描述（改编自申请人摘要）：高血压患者 对运动的耐受性有限，但这是机械性的原因， 限制并不明确。 来自PI实验室的长期研究 仪器狗表明，在运动过程中， 收缩张力与共存的代谢和内皮介导的竞争 冠状血管系统的血管舒张。 这些研究表明， 在肾血管病变的犬中，冠状动脉收缩张力被夸大 高血压 这项研究的目的是确定肾上腺素能和 负责大冠状血管的神经体液机制 肾血管性高血压后的抵抗力。 一般的假设是 肾血管性高血压改变了神经、旁分泌和 冠状动脉循环的自分泌控制系统 血管收缩剂输入和血管舒张剂影响的衰减。 这些 改变会引起过度的血管收缩反射影响， 冠状血管和降低的增加冠状血流的能力。 的 申请人提出，肾血管性高血压引起的失衡 在血管收缩和扩张机制中， 心肌工作效率和增加的心肌敏感性 低灌注和缺血，特别是在运动期间。 远景目标 是为了证明冠状动脉血流调节是 神经、激素和内皮控制机制之间的相互作用。 然而，这个概念是，在病理生理条件下， 这些控制机制之间的平衡被改变， 血管收缩占主导地位。 申请人表示， 这些实验应该解决关于改变的基本问题 在交感神经系统和内皮功能和机制， 肾血管性高血压改变了这些系统。 申请人 还表明，这些研究应该澄清的机制的理由， 用于治疗高血压患者的不同药物疗法。 的 以下假设将在体内使用有意识的 仪器狗和体外使用离体冠状动脉血管模型。 第一章 肾血管性高血压增加静息时冠状动脉血管收缩， 在运动过程中，心肌，特别是内皮细胞， 与氧气需求量有关的低灌注。 2)肾血管 高血压引起的冠状动脉血管功能的变化是由于 血管神经体液控制机制的适应。

DESCRIPTION (Adapted from the applicant's abstract): Hypertensive patients have a limited tolerance to exercise, but the mechanistic reasons for this limitation are not clear. Studies from the PI's laboratory in chronically instrumented dogs indicate that during exercise an alpha1 - adrenergic constrictor tone competes with coexisting metabolic and endothelial mediated vasodilation in the coronary vasculature. These studies indicate that a coronary constrictor tone is exaggerated in dogs with renovascular hypertension. The goal of this proposal is to determine the adrenergic and neurohumoral mechanisms responsible for the greater coronary vascular resistance after renovascular hypertension. The general hypothesis to be tested is that renovascular hypertension alters the neural, paracrine and autocrine control systems of the coronary circulation through exaggeration of vasoconstrictor inputs and attenuation of vasodilator influences. These alterations would cause exaggerated vasoconstrictor reflex influences on the coronary vessels and a reduced ability to increase coronary blood flow. The applicant proposes that the renovascular hypertension-induced imbalance among vasoconstrictor and dilator mechanisms results in a reduction in myocardial work efficiency and an increased susceptibility to myocardial hypoperfusion and ischemia, especially during exercise. The long-range goal is to demonstrate that coronary blood flow regulation is the result of interactions between neural, hormonal and endothelial control mechanisms. However, the concept is that under pathophysiological conditions, the balance between these control mechanisms is altered such that vasoconstriction dominates. The applicant indicates that the results of these experiments should address fundamental questions regarding alterations in sympathetic nervous system and endothelial function and the mechanisms by which these systems are altered by renovascular hypertension. The applicant also suggests that these studies should clarify the mechanistic rationale for different medical therapies to treat patients with hypertension. The following hypotheses will be tested both in vivo using conscious instrumented dogs and in vitro using isolated coronary vessel models. 1) Renovascular hypertension increases coronary vasoconstriction at rest and during exercise such that the myocardium, specifically the endocardium, becomes hypoperfused in relation to oxygen demand. 2) Renovascular hypertension induced changes in coronary vascular function are due to adaptations in the vascular neural-humoral control mechanisms.