Article Text

  1. V. S. Chhokar1,
  2. Y. Sun1,
  3. S. K. Bhattacharya1,
  4. R. A. Ahokas1,
  5. L. K. Myers1,
  6. Z. Xing1,
  7. R. A. Smith1,
  8. I. C. Gerling1,
  9. K. T. Weber1
  1. 1Memphis, TN.


Purpose In congestive heart failure (CHF), aldosteronism may induce a syndrome that features oxi/nitrosative stress, a proinflammatory phenotype, soft tissue and bone wasting. We hypothesized aldosterone/1% NaCl treatment (ALDOST) in rats enhances urinary and fecal Ca2+ and Mg2+ excretion and leads to systemic effects, including secondary hyperparathyroidism (SHPT).

Methods At 1, 2, 4 and 6 weeks of ALDOST we monitored Ca2+ and Mg2+ excretion; ionized [Ca2+]o and [Mg2+]o, parathyroid hormone (PTH) and α1-antiproteinase activity (α1-AP) in plasma; bone mineral density (BMD) and bone strength (BS); total intracellular Ca2+ and Mg2+ in peripheral blood mononuclear cells (PBMC) and ventricular tissue; lymphocyte H2O2 production; and NADPH oxidase activation in ventricular tissue. A separate group received spironolactone (Spi), an aldosterone receptor antagonist. Age-/gender-matched unoperated and untreated rats served as controls.

Results ALDOST induced a marked (p < .05) and persistent rise (3-5 fold) in both 24 hour urinary and fecal Ca2+ and Mg2+ excretion at weeks 1-6, together with progressive reductions (p < .05) in plasma [Ca2+]o and [Mg2+]o, and elevation (p < .05) in PTH. A fall (P < .05) in BMD and BS was seen at weeks 4 and 6. An early, sustained increase (p < .05) in PBMC Ca2+ and Mg2+ and increase (p < .05) in ventricular tissue Ca2+ was seen at weeks 4 and 6 Plasma α1-AP activity was reduced (p < .05) while lymphocyte H2O2 production was increased (p < .05) at all time points and gp91phox-positive inflammatory cells invaded the perivascular space of intramural coronary arteries of both ventricles at weeks 4 and 6. Spi co-treatment attenuated (p < .05) urinary and fecal Ca2+ and Mg2+ excretion, prevented the fall in [Ca2+]o and [Mg2+]o, rescued BMD and BS, and prevented Ca2+ loading of PBMC and cardiomyocytes.

Conclusions Aldosteronism promotes urinary and fecal Ca2+ and Mg2+ excretion leading to a fall in plasma ionized [Ca2+]o and [Mg2+]o with SHPT and bone resorption. PTH-mediated Ca2+ loading of PBMC and cardiac tissue induces oxi/nitrosative stress and results in a proinflammatory phenotype. SHPT accounts for this Ca2+ paradox and contributes to the pathophysiology of CHF with aldosteronism. This work was supported, in part, by NIH Training Grant GR HL07641 (to V.S.C.).

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