The diuretic effects of large doses of acetazolamide and an analog lacking carbonic anhydrase inhibiting activity.

According to current concepts, acidification of the urine in the distal tubule and final removal of bicarbonate from the glomerular filtrate occur by a process of ion exchange in which hydrogen ions within tubular cells are exchanged for sodium in the filtrate (1). It is thought that carbonic anhydrase catalyzes an essential reaction which either directly supplies hydrogen ions to the exchange site or removes the base generated by the secretion of hydrogen ions. In support of this hypothesis is the fact that unsubstituted sulfonamides which inhibit carbonic anhydrase prevent acidification of the urine and produce a diuresis of sodium and bicarbonate. Using sulfanilamide, Pitts and Alexander found that approximately 20 per cent of the filtered bicarbonate could be diverted into the urine (2), and suggested that the reabsorption of bicarbonate in the distal tubule was dependent on carbonic anhydrase activity. Subsequently, however, it was pointed out by Berliner (3) and by Schwartz, Danzig and Relman (4) that acetazolamide, a more potent sulfonamide inhibitor of carbonic anhydrase, is capable of producing much greater effects on bicarbonate reabsorption. A dose of 20 to 30 mg per kg of acetazolamide resulted in the loss of up to 50 per cent of the filtered bicarbonate, thus suggesting that a