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. Methods and 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 alpha(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 alpha(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.