Loss of bone minerals and strength in rats with aldosteronism

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 287; no. 5; pp. H2023 - H2026
• Main Authors: Chhokar, Vikram S, Sun, Yao, Bhattacharya, Syamal K, Ahokas, Robert A, Myers, Linda K, Xing, Zhiqing, Smith, Richard A, Gerling, Ivan C, Weber, Karl T
• Format: Journal Article
• Language: English
• Published: United States 01.11.2004
• Subjects: alpha 1-Antitrypsin - metabolism; Animals; Bone and Bones - metabolism; Bone Density; Calcium - blood; Calcium - metabolism; Calcium - urine; Hyperaldosteronism - metabolism; Hyperaldosteronism - physiopathology; Magnesium - blood; Magnesium - metabolism; Magnesium - urine; Muscle, Skeletal - physiopathology; Rats; Rats, Sprague-Dawley
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00477.2004

Divisions of 1 Cardiovascular Diseases and 2 Endocrinology, Department of Medicine; and Departments of 3 Surgery, 4 Obstetrics and Gynecology, 5 Pediatrics, and 6 Orthopaedic Surgery, University of Tennessee Health Science Center, Memphis, Tennessee 38163 Submitted 25 May 2004 ; accepted in final form 24 June 2004 Congestive 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 + ) 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 2+ and Ca 2+ ; urinary Mg 2+ and Ca 2+ excretion; and bone mineral composition and strength to flexure stress. Compared with controls, we found reductions in plasma 1 -antiproteinase activity and ionized Mg 2+ and Ca 2+ together with persistently elevated urinary Mg 2+ and Ca 2+ excretion, a progressive loss of bone mineral density and content with reduced Mg 2+ and Ca 2+ 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 Address for reprint requests and other correspondence: K. T. Weber, Division of Cardiovascular Diseases, Univ. of Tennessee Health Science Center, 920 Madison Ave., Third Floor, Memphis, TN 38163 (E-mail: KTWeber{at}utmem.edu )