CIRCULATORY CONTROL IN CHRONIC HYPOTENSIVE STATES

这些研究将在两个方面定义循环控制的基本机制 慢性直立性高血压的临床综合征。 这些患者 通常严重丧失能力;治疗仅部分有效， 伴随着严重的副作用。 交感神经强直性直立性 低血压（SOH），在临床上与“血管调节性”重叠，或 “神经循环”无力和部分二尖瓣脱垂 和植物神经功能异常性直立性低血压（DOH），包括 特发性体位性低血压（IOH）和多系统 萎缩（MSA），表现出错误的心血管控制。 这些研究将 不仅提供关于这些控制异常的信息，而且 有可能改善治疗。 我们将比较SOH患者和同期研究的对照组，使用 多种技术来研究的贡献的一些方面， 循环控制对这些患者的立位不耐受的影响。 我们 将定义密度，亲和力和α-和 与放射性配体结合的循环血细胞上的β-肾上腺素受体， 特别是检查对生理动作的反应。 我们将 测量前臂血流量、电阻和电容，以研究 血管平滑肌对肾上腺素能和非肾上腺素能的反应 激动剂 电子照相技术将使我们能够精确测量 对压力感受器刺激的外周交感神经流出反应。 最后，我们将严格评估受控期间的血管内容量 钠摄入量与肾素、血管紧张素和心房肌收缩反应 利钠因子和容量控制。 在DOH患者中，我们将利用一些药理学方法， 操纵神经递质水平以增强交感神经流出， 立位耐力 我们将使用乙酰胆碱抑制剂， 升高外周和中枢ACh水平， 交感神经张力增强的显微神经造影和血流动力学研究 应答 加入外周作用的毒蕈碱拮抗剂 增强交感效应。 我们会雇用中央 α 2-肾上腺素受体阻滞剂增强交感神经流出，然后 用单胺氧化酶抑制剂“保护”增加的去甲肾上腺素水平。 一 最后一步将是中枢α 2-阻断与MAO的组合， 胆碱酯酶抑制 我们将使用类似的方法来探讨作用 中枢α 2肾上腺素受体在直立性低血压中的作用 左旋多巴疗法

These studies will define basic mechanisms of circulatory control in two clinical syndromes of chronic orthostatic hypertension. These patients are often severely incapacitated; therapy is only partially effective and is attended by significant side effects. Both sympathotonic orthostatic hypotension (SOH), which overlaps clinically with "vasoregulatory" or "neurocirculatory" asthenia and a portion of the mitral valve prolapse population, and dysautonomic orthostatic hypotension (DOH), including patients with idiopathic orthostatic hypotension (IOH) and multiple system atrophy (MSA), exhibit faulty cardiovascular control. These studies will not only provide information about these abnormalities of control, but also have the potential to improve therapy. We will compare patients with SOH and concomitantly studied controls, using multiple techniques to study the contribution of a number of aspects of circulatory control to the orthostatic intolerance of these patients. We will define the density, affinity and regulation of alpha- and beta-adrenoreceptors on circulating blood cells with radioligand binding, examining in particular responses to physiologic maneuvers. We will measure forearm blood flow, resistance and capacitance to study the responses of vascular smooth muscle to adrenergic and non-adrenergic agonists. Microneurographic techniques will allow us to measure precisely the peripheral sympathetic outflow response to baroreceptor stimulation. Finally, we will critically assess intravascular volume during controlled sodium intake and the responses of renin, angiotension and atrial natriuretic factor to volume manipulation. In patients with DOH, we will utilize a number of pharmacologic methods to manipulate neurotransmitter levels to enhance sympathetic outflow and orthostatic tolerance. We will use acetylcholinestnese inhibition to elevate peripheral and central levels of ACh, defining potential enhancement of sympathetic tone with microneurography and hemodynamic responses. The addition of a peripherally-acting muscarinic antagonist enhance the sympathetic effect. We will employ central alpha2-adrenoreceptor blockade to enhance sympathetic outflow, and then "protect" the increased norepinephrine levels with an MAO inhibitor. A final step will be the combination of central alpha2-blockade with MAO and cholinesterase inhibition. We will use similar methods to explore the role of central alpha2-adrenoreceptors in the orthostatic hypotension produced by levodopa therapy.