Post-Exercise Hypotension: Central Sites and Mechanisms

描述（申请人摘要）：高血压患者的单次运动 受试者可导致交感神经活动的长期减少， 导致运动后低血压（PEH）， 压力PEH需要一个完整的压力反射系统;但是，系统的增益 在调节交感神经活动中的作用降低。尽管潜在 治疗的好处是赞赏，机制，其中锻炼， 高血压受试者导致高血压的持续降低 通过减少中枢交感神经输出，同时 交感神经输出的压力反射控制的降低的增益是未知的。目标 这一建议的目的是解决这些机制。我们的数据表明，PEH和 减少的增益是由运动引起的中枢神经系统的变化介导的。 压力反射网络，特别是，在孤束核（NTS）， 压力感受器信号首先被处理，并且在交感心血管 延髓头端腹外侧区（RVLM）的神经元，交感神经输出 通路我们提出两个具体假设：1。PEH的基础是 RVLM交感心血管神经元的冲动活动减少， 减少介导的：a）紧张性增加的冲动活动， 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GABAA-RS受体（GABAA-RS）），和B）RVLM GABAA-RS的上调 （增强对RVLM的紧张性GABA抑制性输入的功效） 神经元）。2.减少的压力反射增益起源于NTS（使得对于 给定血压和压力感受器输入的变化， 在NTS神经元输出（因此RVLM中的动态GABA释放）减少。 本研究将通过四个目标，使用NTS的细胞外记录来检验假设 和RVLM神经元活动的中枢压力反射网络在体内; 在含有NTS和RVLM神经元的延髓切片中进行膜片钳 中央网络;和实时RT-PCR从NTS和RVLM微穿孔， 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和目的3-4 将阐述NTS中介导PEH的突触前和突触后机制， 降低的增益。

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.