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: 6112485
• 负责人: MICHAEL J JOYNER
• 金额: $ 19.07万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2000-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112485
• 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 直立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 立位应力引起的神经活动和外周血管反应 患有血管迷走神经性晕厥的反复发作或 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，心肺“过度刺激” 机械感受器引起血管收缩中心的显著抑制， 随后的心动过缓和交感神经的不适当下降 血管收缩活性的外周。 在POTS中，患者表现为 站立时明显心动过速，可能与 直立姿势时外周血管收缩不足。 总 在这两个患者组中研究的假设是， 应激引起交感血管收缩剂流出不足， 外周血管收缩不充分，对正常的 交感神经在立位应激时的流出。 此外，在vasovagal 晕厥时，一个主要的未解决的问题是， 发生在晕厥是交感神经撤回或积极的结果 血管舒张 这些概念将通过解决以下问题来研究 具体目标：具体目标1 -什么是时间和数量 中心静脉压，动脉血压， 小腿顺应性、肌肉交感神经活动、心率和前臂 下肢负压时的血管阻力 复发性血管迷走性晕厥 具体目标2 -时间和 中心静脉压、动脉血 压力，小腿顺应性，肌肉交感神经活动，心率， 下肢负压时前臂血管阻力的变化 有POTS的患者？ 具体目标3 -神经介导的一氧化氮 (NO)释放有助于观察到的显著外周血管舒张 血管迷走神经性晕厥的症状吗 这些具体目标将在 正常人和复发性血管迷走性晕厥或POTS患者 在由下体负压（LBNP）引起的静脉汇集期间。 在静脉汇集期间，动脉血压、中心静脉 压力、前臂血流量、小腿顺应性和肌肉交感神经 活动将被测量。 在一些研究中，局部麻醉阻滞 星状神经节将被用于消除自主神经流出到上部 上肢的 在其他研究中，一氧化氮合酶抑制剂将被用于 注入肱动脉，以评估一氧化氮的贡献 在精神应激和血管迷走神经刺激期间氧化物对外周血管舒张的影响 晕厥。 这些研究的执行将提供机械信息 关于直立时血管阻力的反射调节 人类的不宽容。