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 Ca 2+ and Mg 2+ excretion and leads to systemic effects, including bone loss. Methods and Results— At 1, 2, 4, and 6 weeks of ALDOST, we monitored Ca 2+ and Mg 2+ excretion, ionized [Ca 2+ ] o and [Mg 2+ ] o , parathyroid hormone and α 1 -antiproteinase activity in plasma, bone mineral density, bone strength, Ca 2+ and Mg 2+ content in peripheral blood mononuclear cells (PBMCs) and ventricular tissue, and lymphocyte H 2 O 2 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 Ca 2+ and Mg 2+ excretion, a progressive reduction ( P <0.05) in [Ca 2+ ] o and [Mg 2+ ] 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 Ca 2+ and Mg 2+ was found, together with an increase ( P <0.05) in tissue Ca 2+ . Plasma α 1 -antiproteinase activity was reduced ( P <0.05), whereas lymphocyte H 2 O 2 production was increased ( P <0.05) at all time points. Spiro cotreatment attenuated ( P <0.05) urinary and fecal Ca 2+ and Mg 2+ excretion, prevented the fall in [Ca 2+ ] o and [Mg 2+ ] o , rescued bone mineral density and strength, and prevented Ca 2+ overloading of PBMCs and cardiomyocytes. Conclusions— In aldosteronism, Ca 2+ and Mg 2+ losses lead to a fall in [Ca 2+ ] o and [Mg 2+ ] o with secondary hyperparathyroidism and bone resorption. Ca 2+ overloading of PBMCs and cardiac tissue leads to oxi/nitrosative stress and a proinflammatory phenotype.