Acidosis inhibits the hypocalcemic effect of acetazolamide

The effect of acetazolamide on calcium metabolism was examined using sham-operated, ureter-ligated and nephrectomized rats. Acetazolamide doses from 10 to 500 mg/kg produced significant hypocalcemic effects in ureter-ligated and nephrectomized rats. However, doses of acetazolamide up to 1000 mg/kg were devoid of hypocalcemic activity when administered to sham-operated rats. Sham-operated rats exhibited an acidotic response to acetazolamide while ureter-ligated rats did not. Attenuation of this drug-induced acidotic response with i.p. injections of tris(hydroxymethyl)amino-methane uncovered a hypocalcemic effect of acetazolamide in sham-operated rats. Also, the hypocalcemia associated with acetazolamide treatment of ureter-ligated rats was negated when an acidosis was induced by prior injection of NH4Cl. These data indicate that the administration of inhibitors of carbonic anhydrase produces a hypocalcemia when a metabolic acidosis is not present.