Loss of bone minerals and strength in rats with aldosteronism

Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2023-6. doi: 10.1152/ajpheart.00477.2004.

Abstract

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 alpha1-antiproteinase activity, which is an inverse correlate of oxidative/nitrosative stress; plasma concentrations of ionized Mg2+ and Ca2+; urinary Mg2+ and Ca2+ excretion; and bone mineral composition and strength to flexure stress. Compared with controls, we found reductions in plasma alpha1-antiproteinase activity and ionized Mg2+ and Ca2+ together with persistently elevated urinary Mg2+ and Ca2+ excretion, a progressive loss of bone mineral density and content with reduced Mg2+ and Ca2+ 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Bone Density*
  • Bone and Bones / metabolism
  • Calcium / blood
  • Calcium / metabolism
  • Calcium / urine
  • Hyperaldosteronism / metabolism
  • Hyperaldosteronism / physiopathology*
  • Magnesium / blood
  • Magnesium / metabolism
  • Magnesium / urine
  • Muscle, Skeletal / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • alpha 1-Antitrypsin / metabolism

Substances

  • alpha 1-Antitrypsin
  • Magnesium
  • Calcium