Sympathetic - Osmotic Interactions in Humans

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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.