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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