NEURAL REGULATION OF VASCULAR RESISTANCE DURING HUMAN ORTHOSTATIC STRESS

人体直立应激期间血管阻力的神经调节

• 批准号: 6243783
• 负责人: MICHAEL J JOYNER
• 金额: $ 17.76万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243783
• 关键词: autonomic disorder; blood pressure; heart rate; human subject; neuroregulation; nitric oxide; nitric oxide synthase; oxidoreductase inhibitor; peripheral blood vessel; postural hypotension; sympathetic nervous system; syncope; tachycardia; vascular resistance; vasodilators

The long-term objective of this research program is to study the failure of neural mechanisms that regulate vascular resistance during orthostatic intolerance in humans. This proposal will study the muscle sympathetic nerve activity and peripheral vascular responses to orthostatic stress in humans who suffer from either recurrent episodes of vasovagal syncope or postural orthostatic tachycardia syndrome (POTS). The current dogma is that, during vasovagal syncope, "over stimulation" of cardiopulmonary mechanoreceptors causes marked inhibition of the vasomotor center and subsequent bradycardia and an inappropriate fall in sympathetic vasoconstrictor activity to the periphery. In POTS, patients manifest marked tachycardia in response to standing that may be related to inadequate peripheral vasoconstriction in the upright posture. The general hypothesis under study in both these patient groups is that orthostatic stress evokes either inadequate sympathetic vasoconstrictor outflow or inadequate peripheral vasoconstriction in response to a normal rise in sympathetic outflow during orthostatic stress. Additionally, in vasovagal syncope, a major unresolved issue is whether the marked vasodilation that occurs during syncope is the result of sympathetic withdrawal or active vasodilation. These concepts will be studied by addressing the following specific aims: Specific Aim 1 - What are the temporal an quantitative relationships between central venous pressure, arterial blood pressure, calf compliance, muscle sympathetic nerve activity, heart rate, and forearm vascular resistance during lower body negative pressure in patients with recurrent vasovagal syncope? Specific Aim 2 - What are the temporal and quantitative relationships between central venous pressure, arterial blood pressure, calf compliance, muscle sympathetic nerve activity, heart rate, and forearm vascular resistance during lower body negative pressure in patients with POTS? Specific Aim 3 - Does neurally mediated nitric oxide (NO) release contribute to the marked peripheral vasodilation observed during vasovagal syncope in humans? These specific aims will be studied in normal humans and patients with either recurrent vasovagal syncope or POTS during venous pooling caused by lower body negative pressure (LBNP). During the venous pooling, arterial blood pressure, central venous pressure, forearm blood flow, calf compliance, and muscle sympathetic nerve activity will be measured. In some studies, local anesthetic block of the stellate ganglion will be used to eliminate autonomic outflow tot he upper extremity. In other studies, nitric oxide synthase inhibitors will be infused into the brachial artery to evaluate the contribution of nitric oxide to peripheral vasodilation during mental stress and vasovagal syncope. Execution of these studies will provide mechanistic information concerning the reflex regulation of vascular resistance during orthostatic intolerance in humans.

这项研究计划的长期目标是研究 立位时调节血管阻力的神经机制 人类的不宽容。这项建议将研究肌肉交感神经 直立性应激引起的神经活动和外周血管反应 患有反复发作的血管迷走性晕厥或 体位性心动过速综合征(POTS)。目前的教条是 在血管迷走性晕厥期间，对心肺的“过度刺激” 机械感受器导致血管运动中枢显着抑制和 随后的心动过缓和交感神经不适当的下降 血管收缩活动到外周。在POTS中，患者表现出 站立反应出现明显的心动过速可能与 直立位时外周血管收缩不足。这位将军 在这两组患者中研究的假说是直立位 应激引起交感神经血管收缩功能不足或 外周血管收缩功能不足，以应对正常的血压升高 立位应激时交感神经流出。此外，在血管迷走神经中 晕厥，一个重大悬而未决的问题是，是否有明显的血管扩张 发生在晕厥期间是交感神经撤退或活跃的结果 血管扩张。我们将通过解决以下问题来研究这些概念 具体目标：具体目标1-时间和数量是什么 中心静脉压、动脉压、 小腿顺应性、肌交感神经活动、心率和前臂 慢性阻塞性肺疾病患者下体负压时的血管阻力 血管迷走性晕厥复发？具体目标2--什么是暂时的和 中心静脉压与动脉血的定量关系 压力，小腿顺应性，肌肉交感神经活动，心率， 和下半身负压时的前臂血管阻力 拿着罐子的病人？特异性靶点3-DO神经细胞介导的一氧化氮 (NO)释放有助于观察到明显的外周血管扩张 在人类血管迷走性晕厥期间？这些具体目标将在#年研究。 正常人和复发性血管迷走性晕厥或POTS患者 在下体负压(LBNP)引起的静脉输注过程中。 在静脉输注过程中，动脉血压、中心静脉 压力、前臂血流量、小腿顺应性和肌交感神经 活动将被测量。在一些研究中，局麻药阻断了 将使用星状神经节来消除自主性流出到上半部 极端。在其他研究中，一氧化氮合酶抑制剂将是 经臂动脉灌注评价一氧化氮的作用 精神应激和血管迷走神经中的氧化物对外周血管扩张的影响 晕厥。执行这些研究将提供机械性的信息 关于立位时血管阻力的反射调节 人类的不宽容。