Sympathetic - Osmotic Interactions in Humans

人类交感神经-渗透相互作用

• 批准号: 7251171
• 负责人: William B Farquhar
• 金额: $ 23.37万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-02-23 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7251171
• 关键词: Acute; Adult; African American; American; Angiotensin II; Animal Model; Animals; Attention; Blood Pressure; Cardiovascular system; Data; Development; Diet; Dietary Sodium; Elderly; Exhibits; Experimental Animal Model; Extracellular Fluid; Functional disorder; Future; Health; High Blood Pressure; Human; Hypertension; Individual; Influentials; Intake; Kidney Diseases; Laboratories; Lead; Link; Literature; Manuscripts; Measures; Muscle; Nerve; Norepinephrine; Osmolalities; Phenotype; Physiology; Plasma; Population; Prevalence; Purpose; Rate; Regulation; Reporting; Research; Resistance; Sodium; Sodium Chloride; Sympathetic Nervous System; Techniques; Testing; Translating; United States; Week; Woman; Work; base; clinically relevant; insight; intravenous administration; mortality; normotensive; older men; osmoreceptor; peroneal nerve; salt intake; salt sensitive; statistics

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.

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。最近的实验动物数据支持这样的观点，即血浆钠浓度的适度增加激活位于中央的渗透受体，从而触发交感神经兴奋。这种交感神经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。这些假设尚未在人体中进行测试，但它们显然具有临床相关性；血压的盐敏感性在正常血压和高血压成年人中都存在，并与死亡率增加有关。因此，本研究的目的是研究盐敏感和盐抵抗高血压患者交感神经系统活动的渗透调节。第一种假设是，与耐盐个体相比，血浆钠和渗透压的增加会导致肌肉交感神经活动和去甲肾上腺素浓度的增加。第二种假设是，在盐敏感个体中，血管紧张素II水平的不适当升高与交感神经流出量升高有关。为了验证这些假设，受试者（40-60岁的男性和女性）将首先参加为期2周的控制钠饮食试验（1周高钠和1周低钠），他们将被分类为“盐敏感”（动态24小时血压变化大于10毫米汞柱）或“盐抵抗”（血压变化小于5毫米汞柱）。然后，这两组不同的受试者将参加一个急性实验室生理学研究（在饮食试验的1个月内），我们将使用3% NaCl静脉输注30分钟来增加血浆钠浓度和渗透压，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，并提供对血压盐敏感性的机制的见解。高血压在美国是一个主要的健康问题；最近的统计数据显示，有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。这个项目的目的是确定为什么盐会增加某些人的血压。

项目成果

Influence of plasma osmolality on baroreflex control of sympathetic activity.

血浆渗透压对交感神经活动的压力反射控制的影响。

• DOI: 10.1152/ajpheart.01383.2006
• 发表时间: 2007
• 期刊: American journal of physiology. Heart and circulatory physiology
• 作者: Wenner,MeganM;Rose,WilliamC;Delaney,ErinP;Stillabower,MichaelE;Farquhar,WilliamB
• 通讯作者: Farquhar,WilliamB