Sympathetic - Osmotic Interactions in Humans

描述(由申请人提供)：这项建议的广泛、长期目标是研究人类交感神经系统活动的渗透调节。在许多疾病状态下都观察到交感神经过度活动，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。虽然压力感受器反射弧是控制交感神经外流的重要机制，但有证据表明，压力感受器“重置”和压力感受器去神经研究表明，还有其他因素参与其中。最近的活体动物模型表明，血浆渗透压在控制短期和长期交感神经活动方面发挥了作用；因此，需要在人类身上进行前瞻性研究来检验这一假设。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。第二个具体目标是确定原发性高血压患者对交感神经活动的渗透控制是否有所不同。假设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性的更大增加。方案：血压正常和高血压的成年人(男性和女性，少数)将被随机分配接受1)60分钟的高渗盐水(3%)输注(旨在提高血浆渗透压约5%)和2)在另一天进行容量/时间控制(0.9%生理盐水)(交叉设计)。在治疗过程中，交感神经活动将通过腓骨显微神经摄影术直接记录。交感神经流出的辅助测量也将被评估(血浆去甲肾上腺素浓度和肢体血管阻力)。由于将进行直接的交感神经记录，这些数据将提供确凿的证据，支持或驳斥血浆渗透压参与控制人类交感神经流出的假设。这些数据也将加深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NIH未来的建议。例如，由于无机盐--主要是氯化钠--对渗透压有重要影响，并大量消耗，这些数据将为研究“盐敏感型高血压”的发病机制提供依据，这一问题在人群中特别常见(例如，黑人高血压患者和老年人)。

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).