Article Text

  1. K. D. Goodwin1,
  2. R. A. Ahokas1,
  3. S. K. Bhattacharya1,
  4. Y. Sun1,
  5. I. C. Gerling1,
  6. K. T. Weber1
  1. 1University of Tennessee Health Science Center, Memphis, TN


Purpose Secondary hyperparathyroidism (SHPT) has been reported in patients hospitalized with untreated congestive heart failure (CHF) as well as those treated medically (Am J Med Sci 2006;331:30). Mechanisms responsible for Ca2+ dyshomeostasis include Ca2+ and Mg2+ wasting in urine and feces associated with aldosteronism and loop diuretic treatment and hypovitaminosis D in housebound individuals because of their effort intolerance. SHPT appears in rats receiving aldosterone (ALDO; 0.75 μg/h) and 1% NaCl in their drinking water (ALDOST), and where elevations in plasma parathyroid hormone (PTH) lead to intracellular Ca2+ overloading in diverse tissues, including peripheral blood mononuclear cells (PBMC). We hypothesized that the SHPT seen in rats receiving ALDOST could be prevented by cotreatment with 1,25(OH)2D3 (calcitriol; 6 ng/d SC) and a diet supplemented with Ca2+ (2.5%) and Mg2+ (0.5%) (CCM).

Methods and Results Eight-week-old male Sprague-Dawley rats received ALDOST alone for 4 weeks or together with CCM. We monitored plasma PTH and ionized [Ca2+]o, cytosolic-free [Ca2+]i, and H2O2 production in PBMC. Compared with age-/gender-matched, untreated controls, we found that ALDOST (mean ± SEM) was accompanied by a reduction (p < .05) in plasma-ionized [Ca2+]o (1.15 ± 0.01 vs 0.86 ± 0.01 mmol/L) and increased (p < .05) plasma PTH (45 ± 6 vs 98 ± 6 pg/mL); increased (p < .05) cytosolic-free [Ca2+]i (41 ± 1 vs 79 ± 7 nmol/L); and increased (p < .001) H2O2 production (79 ± 2 vs 154 ± 3 mcb). The CCM regimen prevented (p < .001) the fall in plasma [Ca2+]o (1.05 ± 0.01 mmol/L) and rise in PTH (58 ± 5 pg/mL), PBMC [Ca2+]i (49 ± 3 nmol/L; p<0.005), and increase in H2O2 production (67 ± 3 mcb; p < .001).

Conclusions The ionized hypocalcemia that accompanies aldosteronism in rats and that contributes to the appearance of SHPT can be prevented by calcitriol and dietary Ca2+ and Mg2+ supplements. In so doing, this regimen prevents PTH-mediated intracellular [Ca2+]i overloading and induction of oxidative stress. These findings raise the prospect that the SHPT found in CHF could be managed with macro- and micronutrients.

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