Abnormalities in baroreflex function and vascular responsiveness may be intrinsic to the pathophysiology of hypertension. Sodium, in particular, may potentiate hypertension-related abnormalities in baroreflex function and vascular reactivity, thus contributing to a rise in blood pressure in patients with this disorder. Indeed, epidemiologic studies have suggested that the prevalence of hypertension is associated with the degree of salt intake. Accordingly, the objectives of this proposal are to determine whether sodium accentuates abnormalities in baroreflex function, and/or vascular responsiveness to vasoconstrictive stimuli in patients with hypertension. Baroreflex function will be examined in 30 healthy, normotensive human subjects and 30 age- and sex- matched hypertensive individuals during maneuvers which alter the loading conditions of the cardiopulmonary and arterial baroreceptors, such as lower body negative pressure, neck positive and neck negative pressure and phenylephrine and nitroprusside infusions. Baroreflex function will be assessed during these interventions by measuring changes in blood pressure, heart rate, regional vascular resistance, as well as indices of neural-hormonal activity. Each subject will be studied during low (10 mEq/d) and high (200 mEq/d) sodium intake. Since sodium-mediated changes in baroreceptor function may be secondary to a decrease in arterial compliance, these subjects will also undergo evaluation of arterial compliance, utilizing measurements of pulse wave velocity, diastolic blood pressure decay and arterial pulse contour analysis. In order to assess the contribution of sodium to vascular reactivity, forearm vascular responses to intra-arterial norepinephrine, angiotensin II and vasopressin will be measured in 45 normotensive and 45 hypertensive subjects during low and high dietary sodium intake. In order to assess the effect of sodium on the vascular response to endogenous levels of these vasoconstrictors, phentolamine, captopril and V1 vasopressin inhibitor will be administered during lower body negative pressure or neck positive pressure. These studies should provide insight into the pathophysiology of sodium-related increases in blood pressure and yield information pertinent to the prevention and treatment of hypertension.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Modified Research Career Development Award (K04)
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Experimental Cardiovascular Sciences Study Section (ECS)
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Brigham and Women's Hospital
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