Hyperparathyroidism and the calcium paradox of aldosteronism.
BACKGROUND
Aldosteronism may account for oxi/nitrosative stress, a proinflammatory phenotype, and wasting in congestive heart failure. We hypothesized that aldosterone/1% NaCl treatment (ALDOST) in rats enhances Ca2+ and Mg2+ excretion and leads to systemic effects, including bone loss.


RESULTS
At 1, 2, 4, and 6 weeks of ALDOST, we monitored Ca2+ and Mg2+ excretion, ionized [Ca2+]o and [Mg2+]o, parathyroid hormone and 1-antiproteinase activity in plasma, bone mineral density, bone strength, Ca2+ and Mg2+ content in peripheral blood mononuclear cells (PBMCs) and ventricular tissue, and lymphocyte H2O2 production. A separate group received spironolactone (Spiro), an aldosterone receptor antagonist. Age- and gender-matched unoperated and untreated rats served as controls. ALDOST induced a marked (P<0.05) and persistent rise in urinary and fecal Ca2+ and Mg2+ excretion, a progressive reduction (P<0.05) in [Ca2+]o and [Mg2+]o, and an elevation in parathyroid hormone (P<0.05) with a fall (P<0.05) in bone mineral density and strength. An early, sustained increase (P<0.05) in PBMC Ca2+ and Mg2+ was found, together with an increase (P<0.05) in tissue Ca2+. Plasma 1-antiproteinase activity was reduced (P<0.05), whereas lymphocyte H2O2 production was increased (P<0.05) at all time points. Spiro cotreatment attenuated (P<0.05) urinary and fecal Ca2+ and Mg2+ excretion, prevented the fall in [Ca2+]o and [Mg2+]o, rescued bone mineral density and strength, and prevented Ca2+ overloading of PBMCs and cardiomyocytes.


CONCLUSIONS
In aldosteronism, Ca2+ and Mg2+ losses lead to a fall in [Ca2+]o and [Mg2+]o with secondary hyperparathyroidism and bone resorption. Ca2+ overloading of PBMCs and cardiac tissue leads to oxi/nitrosative stress and a proinflammatory phenotype.
Chhokar
Vikram S
VS
Division of Cardiovascular Diseases, University of Tennessee Health Science Center, 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
D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000209:etiology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D006929:Hyperaldosteronism / Q000150:complications* / Q000378:metabolism*; D006961:Hyperparathyroidism / Q000209:etiology*; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008274:Magnesium / Q000032:analysis / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000008:administration & dosage / Q000494:pharmacology
D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D000450:Aldosterone; D008274:Magnesium; D002118:Calcium