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71 CALCIUM AND MAGNESIUM HOMEOSTASIS IN ALDOSTERONISM: RESPONSE TO DIURETICS
  1. P. H. Law1,
  2. Y. Sun1,
  3. S. K. Bhattacharya1,
  4. K. T. Weber1
  1. 1Memphis, TN.

Abstract

Purpose Loop diuretics, such as furosemide (F), are commonly used in patients with congestive heart failure, where chronic, inappropriate (relative to dietary Na+) elevations in plasma aldosterone (ALDO) are expected, together with a wasting of soft tissues and bone. We hypothesized aldosteronism is accompanied by increased urinary excretion of Ca2+ and Mg2+ that ultimately leads to bone loss and this scenario would be aggravated with F while spironolactone, an ALDO receptor antagonist, would attenuate this loss.

Methods We monitored: 24 hour urinary Ca2+ and Mg2+ excretion; plasma ionized [Ca2+]o and [Mg2+]o and plasma K+; and bone mineral density of femur. The following groups (n = 5) were studied: age-/gender-matched, untreated and F-treated controls; 4 weeks aldosterone/salt treatment (ALDOST, 0.75 μg/h+dietary 1% NaCl/0.4% KCl); 4 weeks ALDOST + F (40 mg/kg in prepared food); and 4 weeks ALDOST + F + spironolactone (Spi; 200 mg/kg/day in divided doses by twice-daily gavage).

Results ALDOST markedly increased (p < .05) urinary Ca2+ and Mg2+ excretion (4969 ± 1078 and 3856 ± 440 μg/24 h, respectively) vs. controls (896 ± 138 and 970 ± 137 μg/24 h); F co-treatment further increased (p < .05) urinary Ca2+ and Mg2+ excretion (6976 ± 648 and 6199 ± 759 μg/24 h, respectively) while Spi co-treatment attenuated (p < .05) these exaggerated losses (4003 ± 515 and 3915 ± 972 μg/24 h). Plasma [Ca2+]o was reduced (p < .05) at week 4 ALDOST + F and in 5 of 5 rats was accompanied by hypokalemia (< 3.4 mmol/L), with each of these responses rescued by Spi co-treatment. Parathyroid hormone (PTH) was increased (p < .05) in ALDOST compared to controls (30 ± 4 vs. 11 ± 3 pmol/mL, respectively) while bone mineral density of femur was decreased (p < .05) at week 4 of ALDOST and ALDOST + F, which was not the case with Spi co-treatment (0.153 ± 0.006, 0.151 ± 0.006 vs. 0.165 ± 0.003 g/cm2, respectively).

Conclusions Hypercalciuria and hypermagnesuria with ALDOST lead to a fall in plasma ionized concentrations of these divalent cations and the elaboration of PTH with secondary hyperparathyroidism accounting for bone resorption. F exaggerates these losses while co-treatment with Spi attenuates Ca2+ and Mg2+ excretion to prevent bone loss. The management of CHF with diuretics should take into consideration their effects on Ca2+ and Mg2+ homeostasis, including their propensity to either promote or prevent bone loss.

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