DIETARY SODIUM: ROLE IN NEURAL CARDIOVASCULAR REGULATION

膳食钠：在神经心血管调节中的作用

• 批准号: 3338522
• 负责人: REGIS R VOLLMER
• 金额: $ 8.04万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-08-01 至 1988-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3338522
• 关键词: autonomic nervous system; baroreceptors; blood pressure; dietary mineral; heart rate; hemodynamics; hormone regulation /control mechanism; neurogenic hypertension; nutrition related tag; reflex; renal hypertension; renin angiotensin system

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.

本提案的实验旨在阐明机制 通过饮食钠摄入影响交感神经系统 控制心脏和脉管系统 的总体目标 该提议是为了检验以下假设：肾素血管紧张素系统（RAS）， 通过其对钠摄入的反应，调节外周 交感神经系统的功能，使交感神经系统的影响， 心血管系统上的神经元对钠的水平是适当的 摄入 这些实验所提供的信息具有重要意义。 饮食中钠摄入模式在糖尿病中的作用 高血压疾病的发展。 此外，更好地了解 将获得的适应交感神经系统的 减少钠摄入量的治疗方式。 这些具体目标 实验是为了确定一系列的饮食钠的影响， 摄入量：1）外周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，包括测量组织含量、合成、释放 和摄取，3）心脏和血管平滑肌对 神经递质（和适当的α-和β-受体激动剂）和4） RAS对交感神经功能的调节，以及5）将 钠摄入量对清醒动物的影响。 完成 为了实现这些目标，将使用三种不同水平的实验系统 的复杂性，并且每个都适合提供独特的信息。 有髓的 大鼠制备物将用于测试外周交感神经元 在缺乏紧张性神经流出和操作反射的情况下， 一个 在体外系统，离体灌流肠系膜，将用于研究 神经节后神经元功能和效应器官反应性 在完整的组织中不存在激素和血流动力学变量， 动物 第三种模型，清醒大鼠将用于测试 交感神经系统最完整的运作方式。 两 在模型中，选择清醒大鼠和去髓大鼠是因为 RAS的激活状态与膳食钠摄入量有关。 因此，可以首先在存在的情况下评估交感神经功能，然后 阻断RAS的影响。 体外系统提供了一种 有机会在缺乏功能的情况下首先研究血管功能， RAS，然后以受控的方式通过施用血管紧张素II。