Sympathetic - Osmotic Interactions in Humans

描述（由申请人提供）：本提案的广泛、长期目标是研究人类交感神经系统活动的渗透调节。实验动物的最新数据支持这样的观点，即血浆钠浓度的适度增加激活了位于中枢的β受体，从而触发交感神经兴奋。这种交感兴奋可能是血压盐敏感性的机制之一。此外，不适当的高血管紧张素II水平可能促进这种交感神经激活。这些假设尚未在人类中进行过测试，但它们显然与临床相关;血压的盐敏感性发生在血压正常和高血压的成年人中，并与死亡率增加有关。因此，本研究的目的是检查盐敏感性和盐抵抗性高血压人的交感神经系统活动的渗透调节。第一个假设是，与耐盐个体相比，血浆钠和渗透压的增加将导致盐敏感个体的肌肉交感神经活性和去甲肾上腺素浓度的更大增加。第二个假设是血管紧张素II水平的不适当升高与盐敏感个体交感神经流出升高有关。为了检验这些假设，受试者（40-60岁的男性和女性）将首先参加为期2周的受控钠饮食试验（1周高钠和1周低钠），其中他们将被分类为“盐敏感”（动态24小时血压变化大于10 mmHg）或“耐盐”（血压变化小于5 mmHg）。然后，这两组不同的受试者将参加一项基于实验室的急性生理学研究（饮食试验的1个月内），我们将使用3% NaCl静脉输注30分钟增加血浆钠浓度和渗透压摩尔浓度，同时记录腓神经的交感神经活动、血浆去甲肾上腺素浓度和血管紧张素II浓度。这些研究将把最近在实验动物模型中的发现转化为人类，并深入了解血压盐敏感性的机制。高血压是美国的一个主要健康问题;最近的统计数据表明，6500万美国人患有高血压。在一些人中，但不是所有人，饮食中的盐会导致血压升高。该项目的目的是确定为什么盐会增加某些人的血压。

DESCRIPTION (provided by applicant): The broad, long-term objective of this proposal is to investigate the osmotic regulation of sympathetic nervous system activity in humans. Recent data in experimental animals supports the view that modest increases in plasma sodium concentration activate centrally located osmoreceptors which trigger sympathoexcitation. This sympathoexcitation may be one of the mechanisms underlying salt sensitivity of blood pressure. Furthermore, inappropriately high angiotensin II levels may facilitate this sympathetic activation. These hypotheses have not been tested in humans, yet they are clearly clinically relevant; salt sensitivity of blood pressure occurs in both normotensive and hypertensive adults, and is associated with increased mortality. Therefore, the purpose of this study is to examine the osmotic regulation of sympathetic nervous system activity in salt sensitive and salt resistant hypertensive humans. The first hypothesis is that increases in plasma sodium and osmolality will lead to greater increases in muscle sympathetic nerve activity and norepinephrine concentration in salt sensitive compared to salt resistant individuals. The second hypothesis is that inappropriately elevated levels of angiotensin II will be associated with elevated sympathetic outflow in salt sensitive individuals. To test these hypotheses, subjects (40-60 year old men and women) will first participate in a 2-week controlled sodium diet trial (1 week high and 1 week low sodium) where they will be classified as "salt sensitive" (greater than a 10 mmHg change in ambulatory 24hr blood pressure) or "salt resistant" (less than a 5 mmHg change in blood pressure). These two distinct groups of subjects will then participate in an acute laboratory-based physiology study (within 1 month of the dietary trial) where we will increase plasma sodium concentration and osmolality using a 3% NaCl intravenous infusion for 30-minutes while recording sympathetic activity from the peroneal nerve, plasma norepinephrine concentration, and angiotensin II concentration. These studies will translate recent findings in experimental animal models to humans, and provide insight into the mechanisms underlying salt sensitivity of blood pressure. High blood pressure is a major health problem in the United States; recent statistics suggest that 65 million Americans have high blood pressure. In some, but not all individuals, dietary salt causes blood pressure to increase. The purpose of this project is to determine why salt increases blood pressures in some individuals.