Calcium paradox of aldosteronism and the role of the parathyroid glands

The hypercalciuria and hypermagnesuria that accompany aldosteronism contribute to a fall in plasma ionized extracellular Ca super(2+) and Mg super(2+) concentrations ([Ca super(2+)] sub(o) and [Mg super(2+)] sub(o)). Despite these losses and the decline in extracellular levels of these cations, total intracellular and cytosolic free Ca super(2+) concentration ([Ca super(2+)] sub(i)) is increased and oxidative stress is induced. This involves diverse tissues, including peripheral blood mononuclear cells (PBMC) and plasma. The accompanying elevation in plasma parathyroid hormone (PTH) and reduction in bone mineral density caused by aldosterone (Aldo)-1% NaCl treatment (AldoST) led us to hypothesize that Ca super(2+) loading and altered redox state are due to secondary hyperparathyroidism (SHPT). Therefore, we studied the effects of total parathyroidectomy (PTx). In rats receiving AldoST, without or with a Ca super(2+)-supplemented diet and/or PTx, we monitored urinary Ca super(2+) and Mg super(2+) excretion; plasma [Ca super(2+)] sub(o), [Mg super(2+)] sub(o), and PTH; PBMC [Ca super(2+)] sub(i) and H sub(2)O sub(2) production; plasma alpha sub(1)-antiproteinase activity; total Ca super(2+) and Mg super(2+) in bone, myocardium, and rectus femoris; and gp91 super(phox) labeling in the heart. We found that 1) the hypercalciuria and hypermagnesuria and decline (P < 0.05) in plasma [Ca super(2+)] sub(o) and [Mg super(2+)] sub(o) that occur with AldoST were not altered by the Ca super(2+)-supplemented diet alone or with PTx; 2) the rise (P < 0.05) in plasma PTH with AldoST, with or without the Ca super(2+)-supplemented diet, was prevented by PTx; 3) increased (P < 0.05) PBMC [Ca super(2+)] sub(i) and H sub(2)O sub(2) production, increased total Ca super(2+) in heart and skeletal muscle, and fall in bone Ca super(2+) and Mg super(2+) and plasma alpha sub(1)-antiproteinase activity with AldoST were abrogated (P < 0.05) by PTx; and 4) gp91 super(phox) activation in right and left ventricles at 4 wk of AldoST was attenuated by PTx. AldoST is accompanied by SHPT, with parathyroid gland-derived calcitropic hormones being responsible for Ca super(2+) overload in diverse tissues and induction of oxidative stress. SHPT plays a permissive role in the proinflammatory vascular phenotype.