CARDIOVASCULAR ADAPTATIONS TO RENOVASCULAR HYPERTENSION

描述（申请人的摘要）：高血压患者具有有限的 运动耐受性，但这种限制的机制尚不清楚。 对长期使用器械的狗的研究表明， 收缩张力与共存的代谢和内皮介导的竞争 运动期间冠状血管系统中的血管舒张。 数据还 表明冠状动脉收缩张力在患有 肾血管性高血压 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。 总的假设是 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通过恶化 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， 冠状动脉血管和增加冠状动脉血流量的能力降低。 我们 提出肾血管性高血压会导致 血管收缩和扩张机制，并导致减少 心肌工作效率和增加心肌敏感性 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， 在病理生理条件下，这些控制之间的平衡 机制被改变，使得血管收缩占主导地位。 的结果 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。 这些研究 应该澄清不同药物治疗的机械原理， 治疗高血压患者。 以下假设使用两个 清醒犬体内和离体冠状动脉模型 将得到解决。 1)肾血管性高血压增加冠状动脉 在休息时和运动期间的血管收缩使得心肌， 特别是内皮细胞，相对于氧气变得低灌注 需求 2)肾血管性高血压引起的冠状动脉病变 功能是由于适应血管神经体液控制 机制等

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.