Purpose Hypozincemia has been found in patients with congestive heart failure (CHF) and may contribute to the appearance of oxidative stress through reduced activity of Cu/Zn-superoxide dismutase (SOD), an antioxidant defense oxidoreductase. In rats with aldosteronism, urinary Zn excretion is increased leading to reduced plasma Zn levels. Mechanisms responsible for the hyperzincuria remain unclear. An acidification of urine with increased ammonia excretion accompanies aldosteronism and leads to its characteristic metabolic alkalosis. Herein we tested the hypothesis that urinary acidification contributes to hyperzincuria and could be attenuated by cotreatment with acetazolamide, a carbonic anhydrase inhibitor that increases urinary HCO3 excretion and pH.
Methods and Results Twenty-four-hour urinary Zn excretion and urine pH were monitored together with serum pH and plasma Zn and Cu/Zn-SOD activity in three groups of Sprague-Dawley rats: unoperated, untreated, age-/gender-matched controls and uninephrectomized rats receiving aldosterone (0.75 μg/h) and 1% NaCl in drinking water (ALDOST) alone or together with acetazolamide cotreatment (75 mg/kg body weight/day by gavage) for 4 weeks. In contrast to controls (mean ± SEM), with ALDOST (p < .05): urinary pH fell (8.10 ± 0.24 vs 6.54 ± 0.13), whereas serum pH rose (7.56 ± 0.02 vs 7.69 ± 0.01); urinary Zn excretion increased (1.86 ± 0.16 vs 8.61 ± 1.04 μg/24 h); and plasma Zn fell (88 ± 1 vs 60 ± 1 μg/dL), as did Cu/Zn-SOD activity (2.51 ± 0.07 vs 2.12 ± 0.08 U/mL). Cotreatment with acetazolamide attenuated (p < .05) urinary acidification (7.15 ± 0.27), and the rise in serum pH (7.52 ± 0.02) and urinary Zn excretion (1.89 ± 0.44 μg/24h) and reduced the fall in plasma Zn (76 ± 3 μg/dL) and prevented the decline in Cu/Zn-SOD activity (2.52 ± 0.17 U/mL).
Conclusions The hyperzincuria that accompanies aldosteronism and that contributes to hypozincemia and reduced Cu/Zn-SOD activity is related to urinary acidification, which can be attenuated by a carbonic anhydrase inhibitor, acetazolamide.
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