RGD Reference Report - Loss of bone minerals and strength in rats with aldosteronism. - Rat Genome Database

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Loss of bone minerals and strength in rats with aldosteronism.

Authors: Chhokar, VS  Sun, Y  Bhattacharya, SK  Ahokas, RA  Myers, LK  Xing, Z  Smith, RA  Gerling, IC  Weber, KT 
Citation: Chhokar VS, etal., Am J Physiol Heart Circ Physiol. 2004 Nov;287(5):H2023-6.
RGD ID: 1643158
Pubmed: (View Article at PubMed) PMID:15475529
DOI: Full-text: DOI:10.1152/ajpheart.00477.2004

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 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.

Annotation

Disease Annotations    

Objects Annotated

Genes (Rattus norvegicus)
Serpina1  (serpin family A member 1)

Genes (Mus musculus)
Serpina1d  (serine (or cysteine) peptidase inhibitor, clade A, member 1D)

Genes (Homo sapiens)
SERPINA1  (serpin family A member 1)


Additional Information