Urinary pCO₂ during carbonic anhydrase inhibition in the dog

The effect of acetazolamide on collecting duct H⁺ secretion was studied by measuring the ability of dogs to generate a high urine-to-blood (U-B) pCo₂ gradient. In hydropenic dogs, acetazolamide administration resulted in a significant increase in urine pCO₂ to the same levels seen in HCO₃-loaded dogs with comparable urine HCO₃ concentrations. Acetazolamide administration to HCO₃-loaded dogs failed to cause a decrease in U-B pCO₂. Administration of tris(hydroxymethyl)aminomethane (Tris) buffer to these dogs resulted in a significant increase in U-B pCO₂ to the same level as that seen in normal HCO₃-loaded dogs receiving Tris. Administration of acetazolamide to dogs with moderately alkaline urine (urine pH 6.4-7.4) failed to either lower or prevent the increase in U-B pCO₂ caused by neutral phosphate infusion. These data demonstrate that acetazolamide does not impair the generation of high U-B pCO₂. We suggest that the ability to generate a normal U-B pCO₂ gradient in the presence of acetazolamide is the result of CO₂ generation via uncatalyzed H⁺ secretion coupled with a decrease in tubular permeability to CO₂ also induced by carbonic anhydrase inhibition.