DIETARY SODIUM: ROLE IN NEURAL CARDIOVASCULAR REGULATION

这一提议的实验旨在阐明这一机制(S) 膳食钠摄入对交感神经系统的影响 心脏和血管系统的控制。《公约》的总体目标 建议测试肾素血管紧张素系统(RAS)， 通过其对钠摄入的反应性，调节外周 交感神经系统的功能使交感神经的作用 心血管系统上的神经元与钠的水平相适应 入口处。这些实验提供的信息具有重要的意义 关于饮食钠摄入模式在健康中的作用 高血压病的发展。此外，更好地理解 将获得交感神经系统对 减少钠摄入量的治疗方式。这些措施的具体目标是 实验是为了确定一系列饮食钠的效果 表现为：1)对周围交感神经的血流动力学反应 刺激，2)交感神经元和肾上腺髓质儿茶酚胺 处置，包括测量组织内容物、合成、释放 和摄取，3)心脏和血管平滑肌对 神经递质(以及适当的α和β受体激动剂)和4) RAS对交感神经功能的调制和5)与 膳食钠摄入量对清醒动物的影响。要完成 为了达到这些目标，将使用三个实验系统，每个实验系统的级别各不相同 都很复杂，每个都适合提供独特的信息。精打细算的 大鼠制剂将用于检测外周交感神经元 在没有紧张性神经外流和手术反射的情况下发挥作用。一个 体外系统，分离的灌流肠系膜，将用于研究 大鼠神经节后神经元功能与效应器官反应性 不存在完整的荷尔蒙和血流动力学变量 动物。第三个模型，清醒的大鼠将被用来测试 以最完整的形式运作交感神经系统。二 在模型中，选择清醒大鼠和脊髓大鼠是因为 RAS的激活状态与膳食钠摄入量有关。 因此，可以首先在在场的情况下评估交感神经功能，然后 在封锁了RAS的影响之后。该体外系统提供了一种 在没有功能障碍的情况下首先研究血管功能的机会 RAS，然后通过给予血管紧张素II控制方式。

The experiments of this proposal are designed to elucidate the mechanism(s) through which dietary sodium intake affects sympathetic nervous system control of the heart and vasculature. The overall objective of the proposal is to test the hypothesis that the renin angiotensin system (RAS), through its responsiveness to sodium intake, modulates peripheral sympathetic nervous system function so that the effects of the sympathetic neurons on the cardiovascular system are appropriate to the level of sodium intake. Information to be provided by these experiments has important implications regarding the role of dietary sodium intake patterns in the development of hypertensive disease. In addition, a better understanding will be gained of the adaptations of the sympathetic nervous system to the therapeutic modality of reducing sodium intake. The specific aims of these experiments are to determine the effects of a range of dietary sodium intakes on: 1) hemodynamic responses to peripheral sympathetic neural stimulation, 2) sympathetic neuronal and adrenal medullary catecholamine disposition, to include measurement of tissue content, synthesis, release and uptake, 3) heart and vascular smooth muscle responsiveness to neurotransmitter (and appropriate alpha- and beta-receptor agonists) and 4) modulation of sympathetic function by the RAS and 5) to relate the influences of dietary sodium intake tothe conscious animal. To accomplish these aims, three experimental systems will be used, each varying in level of complexity, and each suited to provide unique information. The pithed rat preparation will be used to test peripheral sympathetic neuronal function in the absence of tonic neural ouflow and operative reflexes. An in vitro system, the isolated perfused mesentery, will be used to study postganglionic neuronal function and effector organ responsiveness in the absence of the hormonal and hemodynamic variables existing in the intact animal. The third model, the conscious rat will be used to test the operation of the sympathetic nervous system in its most complete form. Two of the models, the conscious rat and pithed rat were selected because the state of activation of the RAS is related to the dietary sodium intake. Thus sympathetic function may be assessed first in the presence and then following blockade of RAS influences. The in vitro system provides an opportunity to study vascular function first in the absence of a functional RAS and then in a controlled fashion by administration of angiotensin II.