CARDIOVASCULAR ADAPTATIONS TO RENOVASCULAR HYPERTENSION

描述（申请人的摘要）：高血压患者的治疗有限 对运动的耐受性，但这种限制的机制尚不清楚。 对长期接受仪器测量的狗的研究表明，α1-肾上腺素能 收缩肌张力与共存的代谢和内皮介导的竞争 运动时冠状动脉血管舒张。 数据还 表明患有以下疾病的狗的冠状动脉收缩音被夸大 肾血管性高血压。 目标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。 总体假设为 测试表明，肾血管性高血压会改变神经、旁分泌和 冠状循环的自分泌控制系统通过恶化 血管收缩剂输入和血管舒张剂影响的减弱。 这些 改变会导致血管收缩反射对血管的影响过大 冠状血管和增加冠状动脉血流量的能力降低。 我们 认为肾血管性高血压导致两者之间的不平衡 血管收缩剂和扩张剂机制并导致减少 心肌工作效率和心肌易感性增加 灌注不足和缺血，尤其是在运动期间。 长远目标 是为了证明冠脉血流调节是以下因素的结果 神经激素和内皮控制机制之间的相互作用，但是 在病理生理条件下，这些控制之间的平衡 机制发生改变，血管收缩占主导地位。 结果 这些实验应该解决有关改变的基本问题 交感神经系统和内皮功能及其机制 这些系统会因肾血管性高血压而改变。 这些研究 应阐明不同医学疗法的机制原理 治疗高血压患者。 以下假设同时使用 体内意识仪器狗和体外分离冠状血管模型 将得到解决。 1) 肾血管性高血压增加冠状动脉 休息时和运动时血管收缩，使心肌， 特别是心内膜，相对于氧气而言变得灌注不足 需求。 2）肾血管性高血压引起冠状血管的变化 功能是由于血管神经体液控制的适应 机制。

DESCRIPTION (Applicant's abstract): Hypertensive patients have a limited tolerance to exercise, but the mechanisms for this limitation are not known. Studies in chronically instrumented dogs indicate that an alpha1-adrenergic constrictor tone competes with coexisting metabolic and endothelial mediated vasodilation in the coronary vasculature during exercise. Data also indicate that a coronary constrictor tone is exaggerated in dogs with renovascular hypertension. The goal is to determine the adrenergic and neurohumoral mechanisms responsible for the greater coronary vascular resistance after renovascular hypertension. The overall hypothesis to be tested is that renovascular hypertension alters the neural, paracrine and autocrine control systems of the coronary circulation through exacerbation 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. We propose that renovascular hypertension causes an imbalance between vasoconstrictor and dilator mechanisms and results in a reduction in myocardial work efficiency and 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 neurohormonal and endothelial control mechanisms, but under pathophysiological conditions, the balance between these control mechanisms is altered such that vasoconstriction dominates. 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. These studies should clarify the mechanistic rationale for different medical therapies to treat patients with hypertension. The following hypotheses using both in vivo conscious instrumented dog and in vitro isolated coronary vessel models will be addressed. 1) Renovascular hypertension increases coronary vasoconstriction at rest and during exercise such that the myocardium, specifically the endocardium, becomes hypoperfused relative to oxygen demand. 2) Renovascular hypertension induced changes in coronary vascular function are due to adaptations in the vascular neural-humoral control mechanisms.