Post-Exercise Hypotension: Central Sites and Mechanisms

描述(申请人摘要)：高血压患者的单次运动 受试者会导致交感神经活性的长期下降， 导致运动后低血压(PEH)，可使高血压病患者恢复正常 压力。Peh需要一个完整的压力反射系统；但是，该系统的收益 在调节交感神经活性方面有所降低。尽管潜在的 治疗的好处是被欣赏的，锻炼的机制是 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 交感神经输出的交感神经反射控制的增益降低是未知的。目标是 这项提议的目的是解决这些机制。我们的数据表明PEH和 这种减少的增益是由运动诱导的中枢神经系统的变化所调节的。 压力感受性反射网络，具体地说，在孤束核 压力感受器信号首先被处理，在交感心血管 延髓头端腹外侧区(RVLM)的神经元是交感神经的输出 路径。我们提出了两个具体的假设：1.PEH的基础是一个 RVLM交感心血管神经元冲动活动降低，a 由以下因素调节的减少：a)补充性增加的冲动活动 压力感受性NTS神经元(增加GABA在GABAA的紧张性释放水平 受体(RVLM神经元上的GABAA-R)，以及b)RVLM GABAA-RS的上调 (放大强直的GABA抑制输入到RVLM的效果 神经元)。2.减少的压力反射增益源自NTS(因此，对于 由于血压和压力感受器输入的变化，相应的变化 在NTS中，神经元输出(因此在RVLM中动态释放GABA)减少。 这些假设将由四个AIMS使用NTS的细胞外记录来验证 RVLM神经元在中枢性压力感受性反射网络中的活动性； 延髓切片上含NTS和RVLM神经元的膜片钳效应 中心网络；来自NTS和RVLM微穿孔的实时RT-PCR 自发性高血压大鼠(SHR)。AIMS 1-2将解决GABA机制 RVLM(GABA释放和GABAA-R基因表达)介导PEH和AIMS 3-4 将探讨NTS中突触前和突触后机制在介导PEH和 减少的收益。

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.