Post-Exercise Hypotension: Central Sites and Mechanisms

运动后低血压：中枢部位和机制

• 批准号: 6317287
• 负责人: ANN C. BONHAM
• 金额: $ 35.63万
• 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/6317287
• 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）：高血压中的单次运动 受试者会导致交感神经活动的长期降低 导致运动后低血压（PEH），可以使高血标准化 压力。 PEH需要完整的BaroreFlex系统；但是，系统的收益 在调节交感神经活动时。虽然潜力 感谢治疗益处，即锻炼的机制 高血压受试者导致高血压持续降低 通过减少中心同情输出，同时到达 减少交感输出的压力反射控制的增益尚不清楚。目标 该提议的是解决这些机制。我们的数据表明PEH和 减少的增益是通过中央运动引起的变化介导的 BaroreFlex网络，特别是在核Tractus solitarius（NTS）中 压力感受器信号首先处理，并在交感神经性心血管处进行 延髓腹侧髓质（RVLM）中的神经元，交感神经输出 路径。我们提出两个特定的假设：1。 RVLM交感神经性心血管神经元的脉冲活性减少，A 减少介导的介导：a）脉冲活性的补品增加 压力感受器NTS神经元（增加GABA释放的补品水平 RVLM神经元上的受体（GABAA-RS）和b）RVLM GABAA-RS的上调 （扩大补品GABA抑制输入对RVLM的功效 神经元）。 2。降低的BaroreFlex增益起源于NTS（因此 鉴于血压和压力感受器输入的变化，相应的变化 在NTS神经元输出中（因此RVLM中的动态GABA释放）减少了。 假设将通过NTS的细胞外记录来通过四个目标进行测试 在体内中央巴罗洛弗网络中的RVLM神经元活动； 在含有NTS和RVLM神经元的髓样切片中贴片夹具 中央网络；以及来自NTS和RVLM Micropunches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并瞄准3-4 将解决NTS中介导PEH的NT和突触后机制 减少增益。