Sympathetic - Osmotic Interactions in Humans

University Of Delaware, Newark DE

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Abstract

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).