Mechanisms Underlying Sodium Intake Mediated Vascular Function

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DESCRIPTION (provided by applicant): Dr. Rhonda Bentley-Lewis is an Instructor in Medicine at Harvard Medical School and an Associate Physician in the Division of Endocrinology, Diabetes, and Hypertension at Brigham and Women's Hospital. Dr. Bentley-Lewis' long-term goal is to become an independent clinical investigator with a focus on the hormonal mechanisms that influence cardiovascular disease risk and to understand how race/ethnicity, gender, and genetics influence this risk. Racial differences in cardiovascular disease have been reported, such as a higher prevalence of hypertension, renal disease, and stroke, in blacks as compared to whites. Mechanisms underlying these differences have not yet been elucidated, although the greater prevalence of salt-sensitive hypertension in blacks suggests an alteration in the interaction of dietary sodium, the hormonal systems reponsive to salt intake, and the vasculature in this population. Subsequently, the current research proposal focuses on the role of the renin-angiotensin-aldosterone system as a potential mediator of the racial differences in the effect of sodium intake on vascular function. The specific aims of this proposal are to test the hypotheses that: 1) high dietary sodium will lead to impairment in vascular function in both blacks and whites but to a greater degree among the blacks; 2) the inadequate suppression of renin-angiotensin-aldosterone system (RAAS) in the setting of high dietary sodium is responsible for the greater impairment in endothelial function seen in blacks compared to whites; and 3) the RAAS-mediated differences in vascular function in blacks are secondary to known genetic differences in RAAS genes between blacks and whites. The results of these investigations would enable us: 1) to characterize vascular function by race and gender in sodium balance; 2) to investigate mechanisms underlying the influence of dietary salt manipulation on vascular function; and 3) to provide pilot data on the role of genetics in mediating these effects. The public health impact is great in that we will be able to appropriately counsel our different patient populations with respect to dietary modifications, thereby optimizing health and minimizing cardiovascular disease risk. Moreover, these insights will benefit not only the management of blood pressure in hypertensives, but also the consideration of cardiovascular disease prevention strategies in normotensives across gender and race.