Adenosine A 1 receptor blockade and the balance of bicarbonate/chloride transport in the proximal tubule

The carbonic anhydrase inhibitor (CAI), benzolamide (BNZ), and adenosine A 1 receptor blocker, KW3902 (KW), are proximal tubular (PT) diuretics. BNZ works by preventing HCO 3 − reabsorption. The transport step(s) inhibited by KW are less defined. The amount of water reabsorbed up to any point along the PT will remain proportional to the total amount of Cl − plus HCO 3 − reabsorbed up to that point. Hence, for a given TF/P inulin in the PT, a greater Cl − reabsorption implies a lesser HCO 3 − reabsorption and vice versa. We employed this principle to look for differences in the mechanism whereby BNZ and KW inhibit proximal reabsorption. Randomly collected tubular fluid along the PT was obtained by micropuncture in rats under control conditions and during systemic infusion of KW and/or BNZ. 3 Hinulin served to mark single nephron GFR (SNGFR) and water reabsorption, Cl − concentrations were determined coulometrically. Relations of fractional Cl − reabsorption (FRCl) to the tubular fluid:plasma inulin ratio (TF/P inulin) were derived by linear regression. A higher regression slope signifies increased dependence of overall reabsorption on active Cl − transport relative to HCO 3 − transport.  The relative contribution of active Cl − transport to overall proximal reabsorption is increased by BNZ but not KW. Therefore, adenosine A 1 receptor blocker and CAI have different, maybe opposing, effects on active Cl − transport in proximal tubular cells. Further, KW increases SNGFR. Therefore, BNZ and KW are not interchangeable as proximal diuretics.