Evidence favoring a role for sodium intake in the pathogenesis of hypertension has arisen from multiple sources. However, it is also clear that therapeutic approaches based on modification of sodium intake or the use of diuretic therapy are only effective in some patients. Our working hypothesis is that sodium-sensitive hypertension is not a homogeneous group, but includes patients with some forms of secondary hypertension (primary aldosteronism bilateral renal artery stenosis, and chronic renal failure), low-renin essential hypertension, and some patients with normal and high-renin essential hypertension. This proposal addresses four specific questions: First, does the blood pressure increment with sodium loading and blood pressure decrement wih diuretic therapy identify the same patient with """"""""salt-sensitive hypertension""""""""? These are the two major criteria for salt sensitivity. Secondly, is there a more simple and precise screening test for salt-sensitive hypertension? Specifically, we plan to assess the level of a number of potentially salt-sensitive biologic indices in normal and hypertensive subjects, including: the ouabain-like inhibitor of sodium/potassium ATPase, a factor which modifies in vitro vascular reactivity, intracellular sodium and/or calcium content and sodium transport in the red cell, platelet angiotensin II (AII) receptor number, and in vivo vascular (particularly renovascular) and adrenal responsiveness to AII. Thirdly, we will examine the effect of changes in dietary sodium intake (sodium dose-response curve) on the above mentioned indices in normal subjects to determine whether there is a hierachical utilization of these various factors as sodium intake changes; is the activation of each an off-on phenomenon of dose related? Finally, we will determine whether the relationship between the level of sodium intake and any of these biologic variables is different between hypertensives versus normal subjects, old versus young, white versus non-white, and whether salt-sensitive hypertensives have a different pattern than salt-insensitive hypertensives. Successful completion of these studies will provide a more rational and practical basis for identifying patients in whom specific recommendations for therapy can be made, provide insight into the mechanism(s) by which sodium intake induces hypertension in some patients, and delineate the underlying abnormalities in these patients.
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