Additive inhibition of renal bicarbonate reabsorption by maleate plus acetazolamide

The effects of two potent inhibitors of renal bicarbonate reabsorption--maleate and acetazolamide--were investigated in the rat using clearance techniques. Acetazolamide given in high dose (50 mg/kg body wt) inhibited fractional bicarbonate reabsorption by ca. 30%, maleate (2.58 nmol/kg body wt) by 25%, and maleate plus acetazolamide by 54-72%. GFR was depressed, and urine volume was increased by both drugs in an additive manner. Maleate was equally effective as inhibitor of HCO3- reabsorption in the presence and absence of carbonic anhydrase activity. It is suggested that the site of action of both drugs is predominantly proximal, but they act on different steps in the transcellular HCO3- transport. A hypothetical mechanism of maleate action is presented, which takes into account the changes in passive HCO3- flux through the basolateral membrane.