Sympathetic - Osmotic Interactions in Humans

人类交感神经-渗透相互作用

• 批准号: 6701137
• 负责人: William B Farquhar
• 金额: $ 22.65万
• 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 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6701137
• 关键词: blood tests; clinical research; essential hypertension; human subject; microelectrodes; neurophysiology; neuroregulation; norepinephrine; osmotic pressure; patient oriented research; sympathetic nervous system; vascular resistance

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. Sympathetic hyperactivity is observed in many disease states, including most forms of hypertension, yet the mechanisms responsible for this increase have not been clearly identified. While the baroreflex arc is an important mechanism controlling sympathetic outflow, evidence demonstrating that baroreceptors "reset" and baroreceptor dennervation studies suggest that other factors are involved. Recent in vivo animal models suggest a role for plasma osmolality in controlling short- and long-term sympathetic activity; thus, prospective studies are needed to test this hypothesis in humans. The first specific aim of this proposal is to determine if changes in osmolality alter indices of sympathetic activity in healthy, normotensive humans. The hypothesis is that increases in plasma osmolality will lead to increases in muscle sympathetic nerve activity. The second specific aim is to determine if the osmotic control of sympathetic activity differs in those with essential hypertension. The hypothesis is that increases in plasma osmolality will lead to greater increases in sympathetic activity in hypertensive compared to normotensive adults. Protocol: Normotensive and hypertensive adults (men and women, minorities) will be randomly assigned to undergo 1) a 60-minute hypertonic saline (3 percent) infusion (designed to raise plasma osmolality approximately 5 percent) and 2) a volume / time control (0.9 percent saline) performed on another day (cross-over design). Sympathetic activity will be directly recorded via peroneal microneurography during the protocol. Ancillary measures of sympathetic outflow will also be assessed (plasma norepinephrine concentration and limb vascular resistance). Because direct sympathetic recordings will be performed, these data will provide firm evidence that either supports or refutes the hypothesis that plasma osmolality participates in the control of sympathetic outflow in humans. These data will also enhance our understanding of the pathophysiology of essential hypertension. Consistent with the goals of the AREA program, the findings from these initial studies will lead to future NIH proposals. For example, because inorganic salts - mainly sodium chloride - contribute importantly to osmolality and are consumed in large quantities, these data will provide the basis for investigating the mechanisms underlying "salt sensitive hypertension", a problem that is especially common in subgroups of the population (e.g., black hypertensives and older adults).

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。 在许多疾病状态中观察到交感神经功能亢进，包括大多数形式的高血压，但导致这种增加的机制尚未明确确定。 虽然压力反射弧是控制交感神经流出的重要机制，但有证据表明压力感受器“重置”和压力感受器去神经支配研究表明还涉及其他因素。 最近的体内动物模型表明血浆渗透压在控制短期和长期交感神经活动中的作用;因此，需要进行前瞻性研究来验证这一假设。 这项建议的第一个具体目标是确定渗透压的变化是否会改变健康血压正常的人的交感神经活动指数。 假设是血浆渗透压的增加将导致肌肉交感神经活动的增加。 第二个具体目标是确定交感神经活动的渗透压控制是否在原发性高血压患者中有所不同。 该假说认为，与血压正常的成年人相比，血浆渗透压的增加将导致高血压患者交感神经活动的更大增加。 协议：血压正常和高血压成人（男性和女性，少数民族）将被随机分配接受1）60分钟高渗盐水（3%）输注（旨在将血浆渗透压升高约5%）和2）另一天进行的体积/时间对照（0.9%盐水）（交叉设计）。 在方案期间，将通过腓神经显微神经造影术直接记录交感神经活动。 还将评估交感神经流出的辅助测量值（血浆去甲肾上腺素浓度和肢体血管阻力）。 由于将进行直接交感神经记录，因此这些数据将提供有力证据，支持或反驳血浆渗透压摩尔浓度参与控制人体交感神经流出的假设。 这些数据也将加强我们对原发性高血压的病理生理学的理解。 与AREA计划的目标一致，这些初步研究的结果将导致未来的NIH提案。 例如，由于无机盐（主要是氯化钠）对渗透压摩尔浓度有重要贡献，并且大量消耗，因此这些数据将为研究“盐敏感性高血压”的潜在机制提供基础，这是一个在人群亚组中特别常见的问题（例如，黑人高血压患者和老年人）。