Loss of bone minerals and strength in rats with aldosteronism.
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.
Chhokar
Vikram S
VS
Division of Cardiovascular Diseases, Univ. of Tennessee Health Science Center, 920 Madison Ave., Third Floor, Memphis, TN 38163, USA.
Sun
Yao
Y
Bhattacharya
Syamal K
SK
Ahokas
Robert A
RA
Myers
Linda K
LK
Xing
Zhiqing
Z
Smith
Richard A
RA
Gerling
Ivan C
IC
Weber
Karl T
KT
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000378:metabolism / Q000652:urine; D006929:Hyperaldosteronism / Q000378:metabolism / Q000503:physiopathology*; D008274:Magnesium / Q000097:blood / Q000378:metabolism / Q000652:urine; D018482:Muscle, Skeletal / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D000515:alpha 1-Antitrypsin; D008274:Magnesium; D002118:Calcium