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。在许多疾病状态中都观察到交感神经过度活跃，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，但证据表明压力感受器“重置”和压力感受器神经支配的研究表明，其他因素也参与其中。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起作用；因此，需要前瞻性研究在人类中验证这一假设。本建议的第一个具体目的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会导致肌肉交感神经活动的增加。第二个具体目的是确定在原发性高血压患者中交感神经活动的渗透控制是否不同。假设是血浆渗透压的增加会导致高血压患者交感神经活动比正常成年人增加更多。方案：正常血压和高血压的成年人（男性和女性，少数民族）将被随机分配接受1)60分钟高渗生理盐水（3%）输注（旨在提高血浆渗透压约5%）和2)另一天进行容量/时间控制（0.9%生理盐水）（交叉设计）。在实验过程中，交感神经活动将通过腓骨微神经造影直接记录下来。还将评估交感神经流出的辅助测量（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，这些数据将提供确凿的证据，支持或反驳血浆渗透压参与控制人类交感神经外流的假设。这些数据也将增强我们对原发性高血压病理生理学的理解。与区域计划的目标一致，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-对渗透压有重要贡献，并且大量消耗，这些数据将为调查“盐敏感性高血压”的机制提供基础，这是一个在人口亚群体中特别常见的问题（例如，黑人高血压和老年人）。

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).