Effects of acetazolamide and metabolic acidosis and alkalosis upon gastric acid secretion

Abstract

The gastric H⁺ secretory responses to i.v. HCl, NaHCO₃, and acetazolamide were studied in Heidenhain-pouch dogs that had been stimulated to secrete by feeding. Acetazolamide in low doses (5 mg/kg) gave a 65% reduction in H⁺ output for 2–4 hr, after which H⁺ secretion increased above normal, coincident with renal HCO₃^– loss and metabolic acidosis. Higher doses produced a greater systemic acidosis and resulted in less initial reduction of H⁺ and greater augmentation. Doses of 75–100 mg/kg, given 17 hr before feeding to produce a systemic acidosis, resulted in increased secretion, even though sufficient drug remained in the plasma to inhibit tissue carbonic anhydrase. Metabolic acidosis (i.v. HCl) initially suppressed but later augmented gastric H⁺. Acetazolamide had no suppressive effect in the presence of either an HCl- or acetazolamide-induced acidosis. Metabolic alkalosis (i.v. NaHCO₃) reduced gastric H⁺ in regular feeding experiments and in dogs made acidotic by acetazolamide.