Abstract

Acetazolamide produces an extracellular metabolic acidosis and K⁺ depletion when two doses of 600 mg/kg are injected 17 hours apart in rats. Intracellular pH measured by 5,5-dimethyloxazolidine-2,4-dione or CO₂ methods is also decreased. In experiments where K⁺ loss is reduced, as by addition of KHCO₃ or 0.5 mg/kg of amiloride, the extracellular acidosis is still observed, but the intracellular pH approaches normal. The metabolic acidosis due to acetazolamide can be corrected by NaHCO₃ but in this situation there is still K⁺ depletion in the extracellular and intracellular compartments. Acetazolamide plus a large (4 mg/kg) dose of amiloridle yields the paradoxical state of extracellular acidosis with an intracellular alkalosis; the latter appears to be correlated with hyperkalemia and high muscle K⁺ caused by K⁺ exit from other tissues. Attempts are made to correlate the various electrolyte changes with the forelimb lesion elicited in rodent offspring when mothers receive high doses of carbonic anhydrase inhibitors on days 10 to 11 of pregnancy. Thus far no single cause has been discovered, but acidosis is probably eliminated. The data suggest that abnormalities in K⁺ balance in either direction may be involved in association with carbonic anhydrase inhibition. Normalization of K⁺ balance in the face of carbonic anhvdrase inhibition abolishes or reduces the lesion.