The concept of """"""""sodium-dependent"""""""" hypertension is based almost entirely on studies in which the dietary intake of sodium (Na+) has been varied by varying the dietary intake of NaC1. The hypertensionogenic effect of dietary Na+ might depend on provision of both Na+ and C1-, not just Na+. If so, """"""""hidden"""""""" sources of dietary Na+, i.e. nonchloride sodium salts such as sodium bicarbonate or ascorbate, may not be as important in the pathogenesis of hypertension as has been widely believed. Comparison of the biologic effects of orally administered NaC1, to those of non-chloride Na+ salts should improve our understanding of the mechanisms of NaC1-dependent hypertenion. In double-blind chronic metabolic balance studies in humans with essential hypertension, we will determine whether supplementing a low NaC1 diet with capsules containing sodium citrate, or a combination of sodium bicarbonate, sodium ascorbate, and sodium phosphate, induces effects on blood pressure (BP) different from those induced by supplementing the same diet with capsules containing an equimolar amount of NaC1. The changes in body weight, extracellular fluid volume, plasma volume, external balances of minerals and electrolytes, and plasma concentrations of renin, aldosterone, catecholamines, parathyroid hormone and calcitriol (1,25-D) will also be determined. In uninephrectomized (UNX) rats given deoxycorticosterone (DOC), we will attempt to determine why provision of a normal amount of dietary Na+ as NaC1 induces hypertension, whereas provision of a greater amount of dietary Na+ as NaHCO3 does not. Specifically, in UNX rats given DOC, we will determine: a) whether provision of a normal amount of dietary Na+ as NaC1 gives rise to greater levels of extracellular fluid volume, cardiac output and or total peripheral resistance than does provision of a greater amount of dietary Na+ as NaHCO3; b) whether a correlation exists between NaC1-induced increases in BP and NaC1-induced increases in 1,25-D (as has been observed in humans with low renin hypertension); c) whether a correlation exists between the antihypertensive effect of supplemental dietary Ca++ and its ability to suppress plasma levels of 1,25-D and whether administration of 1,25-D can exacerbate NaC1-induced hypertension without inducing hypercalcemia, and d) whether oral administration of NaHCO3, which decreases the urinary excretion of calcium (UCaV), induces a lesser increase in 1,25-D than that induced by oral administration of NaC1 and whether supplementing the diet with NaHCO3 can attenuate dietary NaC1-induced increases in UCaV, 1,25-D, and BP.
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