The overall long-term goal of this project remains to study interactions between autonomic and metabolic mechanisms involved in cardiovascular regulation. In this funding period the focus of this application is to test the hypothesis that sympathetic activation contributes to impaired nitric oxide (NO) function in obesity hypertension. Impaired NO function is present in obesity and is proposed as a primary mechanism contributing to the high prevalence of hypertension in this condition. We have also documented impaired NO-mediated vasodilation in "intact" obese hypertensives, but NO impairment is no longer evident if autonomic influences are removed with ganglionic blockade. We propose, therefore, that sympathetic activation is the primary event in obesity hypertension, leading to secondary impairment of NO function. If our hypothesis is true, then the impaired NO function present in obesity can be restored with acute autonomic withdrawal (Specific Aim 1);conversely, impaired NO function can me mimicked in lean controls by adrenergic stimulation (Specific Aim 2), and;targeting sympathetic activation in the treatment of obesity hypertension will improve NO function and related derangements (Specific Aim 3). Our goal is to improve our understanding of the pathophysiological interaction between nitric oxide and the autonomic nervous system, and to provide the knowledge base that will ultimately impact the treatment of obesity hypertension.

Public Health Relevance

Obesity-associated hypertension is a growing medical problem contributing to greater health care costs. Our proposal will investigate how two important systems involved in blood pressure regulation, the autonomic nervous system and nitric oxide, contribute to obesity hypertension. Our ultimate goal is to apply this knowledge to improve the treatment of obesity hypertension.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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Vanderbilt University Medical Center
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