gestive heart failure (CHF) is a clinical syndrome with origins rooted in a salt-avid state largely mediated by effector hormones of the circulating renin-angiotensin-aldosterone system. Other participating neurohormones include catecholamines, endothelin-1, and arginine vasopressin. CHF is accompanied by a systemic illness of uncertain causality. Features include the appearance of oxidative/nitrosative stress and a wasting of tissues including bone. Herein we hypothesized that inappropriate (relative to dietary Na ϩ ) elevations in plasma aldosterone (Aldo) contribute to an altered redox state, augmented excretion of divalent cations, and in turn, a loss of bone minerals and strength. In uninephrectomized rats that received chronic Aldo and 1% NaCl treatment for 4 -6 wk, we monitored plasma ␣1-antiproteinase activity, which is an inverse correlate of oxidative/nitrosative stress; plasma concentrations of ionized Mg 2ϩ and Ca 2ϩ ; urinary Mg 2ϩ and Ca 2ϩ excretion; and bone mineral composition and strength to flexure stress. Compared with controls, we found reductions in plasma ␣1-antiproteinase activity and ionized Mg 2ϩ and Ca 2ϩ together with persistently elevated urinary Mg 2ϩ and Ca 2ϩ excretion, a progressive loss of bone mineral density and content with reduced Mg 2ϩ and Ca 2ϩ concentrations, and a reduction in cortical bone strength. Thus the hypermagnesuria and hypercalciuria that accompany chronic Aldo-1% NaCl treatment contribute to the systemic appearance of oxidative/nitrosative stress and a wasting of bone minerals and strength. aldosterone; congestive heart failure; peripheral blood mononuclear cells; antiproteinase; parathyroid hormone CONGESTIVE HEART FAILURE (CHF), a clinical syndrome with characteristic signs and symptoms, arises from circulating renin-angiotensin-aldosterone system activation (38) and is accompanied by a systemic illness that includes oxidative/ nitrosative stress in the heart, systemic organs, circulating immune cells, and blood (10,20,34,37) and a catabolic state with wasting of lean tissue, fat, and bone (2, 3, 22, 32). Aldosteronism in rats, which is defined as inappropriate (relative to dietary Na ϩ ) and chronic elevations in plasma aldosterone (Aldo) comparable to those seen in CHF, ultimately leads to a proinflammatory coronary vascular phenotype with evidence of oxidative/nitrosative stress (e.g., 3-nitrotyrosine labeling) in invading inflammatory cells (36). These vascular lesions are preceded by an immunostimulatory state that involves activated peripheral blood mononuclear cells (PBMCs) and is induced by Ca 2ϩ loading and transduced by reactive oxygen species in these cells (1, 16). Herein we hypothesized that enhanced urinary excretion of Mg 2ϩ and Ca 2ϩ accompanies chronic Aldo with 1% NaCl treatment (Aldost) and leads to yet another component of this illness, namely, bone wasting.
MATERIALS AND METHODSMale 8-wk-old Sprague-Dawley rats (Harlan, IN) were used in this study, which was approved by the institution's Animal Care and Use Committee. Unoperated and untr...
