MODULATION OF BARORECEPTOR REFLEXES

摘要：这是一份延长优异奖的申请。 一 我们实验室的主要目标在此期间的赠款一直使用 显微神经造影术，以促进对调节反射因素的理解 控制人类的肌肉交感神经活动（MSNA）。 几 本研究提出了新的概念：1）持续刺激 动脉压力感受器的抑制期延长 MSNA在人类; 2）主动脉和心房压力感受器有助于 对人类MSNA的调节很重要; 3）源于 腿部的肌肉传入产生了不同的MSNA反应， 源自手臂肌肉传入的冲动; 4）β肾上腺素能 机制促进精神压力期间MSNA反应的增加; 5)内源性阿片类物质调节MSN的心肺压力反射控制; 耐力运动训练使肌肉元反射脱敏 肌肉酸中毒 现在计划进行研究，将这项工作扩展到五个原始国家中的每一个。 调查领域。 首先我们计划确定这种现象 动脉压力感受器对MSNA的长期抑制作用减弱 在高血压人群中，如果通过给予 纳洛酮 其次，我们计划确定心房压力感受器反射是否 心肌肥大患者的MSNA控制受损， 特别是心房疾病。 第三，我们计划系统地研究 在手臂和腿部运动期间同时记录手臂和腿部MSNA 和运动后循环停止，以测试新的概念， 源于腿部肌肉的传入冲动与手臂肌肉触发 基本上不同的自主调整模式，包括MSNA 应答 第四，我们要判断计划是否出现急性期的现象， 调节MSNA对精神应激反应的β-1受体拮抗剂 在长期口服β受体 拮抗剂，如果这种现象是拮抗剂特有的， 很容易穿过血脑屏障 我们还计划确定， 用纳洛酮阻断内源性阿片类药物可增强MSNA对 精神压力 第五，计划进行研究以确定双臂是否 耐力运动训练减弱了MSNA对手臂循环的反应。 这些研究将采用相同的一般实验方法， 和方法在原来的应用程序应进一步推进我们的 了解调节人类MSNA的因素。

ABSTRACT: This is an application for extension of a MERIT Award. A major goal of our laboratory during this grant period has been to use microneurography to advance understanding of factors that modulate reflex control of muscle sympathetic nerve activity (MSNA) in humans. Several new concepts have emerged from this research: 1) sustained stimulation of arterial baroreceptors is followed by an extended period of inhibition of MSNA in humans; 2) aortic and atrial baroreceptors contribute importantly to regulation of MSNA in humans; 3) impulses originating in muscle afferents in the leg produced different MSNA responses than impulses originating in muscle afferents in the arm; 4) beta adrenergic mechanisms facilitate increases in MSNA responses during mental stress; 5) endogenous opioids modulate cardiopulmonary baroreflex control of MSN; and 6) endurance exercise training desensitizes the muscle metaboreflex to muscle acidosis. Studies are now planned to extend this work in each of the five original areas of investigation. First, we plan to determine if the phenomenon of prolonged inhibition of MSNA by arterial baroreceptors is attenuated in hypertensive humans and if it is prevented by administration of naloxone. Second, we plan to determine if atrial cardiac baroreflex control of MSNA is impaired in patients with cardiac hypertrophy and specifically atrial disease. Third, we plan systematic studies of simultaneous recordings of arm and leg MSNA during arm and leg exercise and post-exercise circulatory arrest to test the novel concept that afferent impulses originating in leg muscles versus arm muscles trigger substantially different patterns of autonomic adjustments including MSNA responses. Fourth, we plan to determine if the phenomenon of acute beta-1 receptor antagonists modulating MSNA responses to mental stress is also observed with chronic oral administration of beta receptor antagonists and if this phenomenon is specific for antagonists which readily cross the blood brain barrier. We also plan to determine if endogenous opioid blockade with naloxone augments MSNA responses to mental stress. Fifth, studies are planned to determine if two arm endurance exercise training blunts the MSNA responses to arm cycling. These studies which will employ the same general experimental approaches and methods in the original application should further advance our understanding of the factors which modulate MSNA in humans.