Post-Exercise Hypotension: Central Sites and Mechanisms

运动后低血压：中枢部位和机制

• 批准号: 6530761
• 负责人: ANN C. BONHAM
• 金额: $ 35.75万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-03-07 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6530761
• 关键词: GABA receptor; baroreflex; brain regulatory center; exercise; gamma aminobutyrate; hypertension; hypotension; laboratory rat; neural transmission; neuroregulation; solitary tract nucleus; spontaneous hypertensive rat; voltage /patch clamp

DESCRIPTION (Applicant's Abstract): Single bouts of exercise in hypertensive subjects can lead to a long-lasting decrease in sympathetic nerve activity that results in a post-exercise hypotension (PEH) which can normalize high blood pressure. PEH requires an intact baroreflex system; but, the gain of the system in regulating sympathetic nerve activity is reduced. Although the potential therapeutic benefits are appreciated, the mechanisms whereby exercise in hypertensive subjects leads to a persistent lowering of high blood pressure through a decreased central sympathetic output and at the same time to a reduced gain of baroreflex control of sympathetic output are unknown. The goal of this proposal is to resolve those mechanisms. Our data suggest that PEH and the reduced gain are mediated by exercise-induced changes in the central baroreflex network, specifically, in the nucleus tractus solitarius (NTS) where baroreceptor signals are first processed and at sympathetic cardiovascular neurons in the rostral ventrolateral medulla (RVLM), the sympathetic output pathway. We pose two Specific Hypotheses: 1. The underpinning of PEH is a decrease in the impulse activity of RVLM sympathetic cardiovascular neurons, a decrease mediated by: a) a tonic increase in the impulse activity of baroreceptor NTS neurons (increasing the tonic level of GABA release at GABAA receptors (GABAA-Rs) on RVLM neurons), and b) an upregulation of RVLM GABAA-RS (amplifying the efficacy of the tonic GABA inhibitory input to the RVLM neurons). 2. The reduced baroreflex gain originates in the NTS (such that for a given change in blood pressure and baroreceptor input, the corresponding change in NTS neuronal output (and hence dynamic GABA release in the RVLM) is reduced. The hypotheses will be tested by four aims using extracellular recording of NTS and RVLM neuronal activity in the central baroreflex network in vivo; patch-clamping in medullary slices containing NTS and RVLM neurons in the central network; and real-time RT-PCR from NTS and RVLM micropunches in spontaneously hypertensive rats (SHR). Aims 1-2 will resolve GABA mechanisms in the RVLM (GABA release and GABAA-R gene expression) mediating PEH and Aims 3-4 will address pre- and postsynaptic mechanisms in the NTS in mediating PEH and the reduced gain.

描述（申请人的摘要）：高血压患者的单次运动 受试者可能会导致交感神经活动长期减少 导致运动后低血压（PEH），使高血压正常化 压力。 PEH 需要完整的压力反射系统；但是，系统的增益 调节交感神经活动的能力降低。虽然有潜力 治疗效果受到赞赏，锻炼的机制 高血压受试者导致高血压持续降低 通过减少中枢交感神经输出，同时 交感神经输出的压力感受反射控制增益减少尚不清楚。目标 该提案的目的是解决这些机制问题。我们的数据表明，PEH 和 增益的减少是由运动引起的中枢变化介导的 压力感受反射网络，特别是在孤束核（NTS）中，其中 压力感受器信号首先被处理并在交感心血管 延髓头侧腹外侧神经元 (RVLM)，交感神经输出 途径。我们提出两个具体假设： 1. PEH 的基础是 RVLM 交感心血管神经元冲动活动减少， 减少由以下因素介导：a）冲动活动的强直增加 压力感受器 NTS 神经元（增加 GABAA 处 GABA 释放的紧张水平） RVLM 神经元上的受体 (GABAA-R))，以及 b) RVLM GABAA-RS 的上调 （增强 RVLM 的强效 GABA 抑制输入的功效 神经元）。 2. 压力反射增益的减少源自 NTS（例如，对于 给定血压和压力感受器输入的变化，相应的变化 NTS 神经元输出（因此 RVLM 中的动态 GABA 释放）减少。 这些假设将通过使用 NTS 细胞外记录的四个目​​标进行检验 以及体内中枢压力反射网络中的 RVLM 神经元活动； 对含有 NTS 和 RVLM 神经元的髓质切片进行膜片钳 中央网络；以及来自 NTS 和 RVLM 微孔的实时 RT-PCR 自发性高血压大鼠（SHR）。目标 1-2 将解决 GABA 机制 RVLM（GABA 释放和 GABAA-R 基因表达）介导 PEH 和目标 3-4 将解决 NTS 中介导 PEH 和突触后机制 减少的增益。