Purpose Patients with the salt-avid state of congestive heart failure (CHF) have been found to have hypozincemia of uncertain origin(s), which may reduce antioxidant defenses provided by Cu/Zn superoxide dismutase (SOD). In rats with aldosteronism, urinary Zn excretion is increased, leading to hypozincemia and reduced plasma Cu/Zn-SOD activity. Whether spironolactone (Spiro), an aldosterone receptor antagonist, would restore plasma Zn levels and Cu/Zn-SOD activity in rats with established hypozincemia remains uncertain.
Methods and Results Uninephrectomized Sprague-Dawley rats received aldosterone (0.75 μg/h) plus 1% NaCl in their drinking water (ALDOST) for 1, 4, and 6 weeks. In a separate group that received ALDOST for 6 weeks, Spiro was begun at week 3 and continued to week 6 (A+Spiro), in a treatment study format. Unoperated, untreated, age-/gender-matched rats served as controls. Plasma Zn and Cu/Zn-SOD activity were monitored at weeks 1, 4, and 6 ALDOST and at week 6 of A+Spiro. We found (mean ± SEM) plasma Zn levels were reduced (p < .05) at weeks 1, 4, and 6 ALDOST (56.5 ± 3.7, 59.7 ± 1.1 and 47.8 ± 2.7 μg/dL, respectively) compared with controls (87.6 ± 1.0 μg/dL), which was related to the hyperzincuria (1.37 ± 0.09 vs 8.61 ± 1.04 μg/24 h) seen with ALDOST. Plasma Cu/Zn-SOD activity was reduced (p < .05) at weeks 1, 4, and 6 ALDOST (1.05 ± 0.11, 1.05 ± 0.06, and 0.85 ± 0.03 U/mL, respectively) compared with controls (1.69 ± 0.10 U/mL). By contrast, urinary Zn excretion was attenuated with A+Spiro (3.85 ± 1.26 μg/24 h), which allowed for the return of plasma Zn to control levels (83.0 μg/dL) and an attenuation of the reduction in plasma Cu/Zn activity (1.27 ± 0.05 U/mL) at week 6.
Conclusions In aldosteronism, the hypozincemia and reduced plasma Cu/Zn-SOD activity that appear due to hyperzincuria can each be corrected by treatment with an aldosterone receptor antagonist, Spiro. The proven utility of Spiro in the management of patients with CHF may include its favorable impact in controlling urinary Zn excretion and restoring serum Zn and antioxidant defenses toward normal levels.
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