REDUCED PROXIMAL REABSORPTION RESETS TUBULOGLOMERULAR FEEDBACK IN EUVOLEMIC RATS

Inhibition of renal carbonic anhydrase reduces proximal reabsorption a nd activates tubuloglomerular feedback (TGF). The TGF response is satu rable, with highest gain focused near the natural flow rate. Therefore , any large change imposed on ambient tubular flow should reduce the T GF response to subequent flow perturbations. However, TGF tends to ali gn with ambient flow regardless of the rate of ambient flow, suggestin g that TGF resets to accommodate changes in flow while maintaining fee dback efficiency. We used micropuncture and videometric flow velocitom etry to test for TGF resetting in free-flowing nephrons during systemi c infusion of the carbonic anhydrase inhibitor benzolamide (BNZ, 5 mg. kg(-1).h(-1)) in euvolemic rats. Late proximal flow (V-LP) and the fra ctional compensation (C) of TGF for perturbations in V-LP were assesse d repeatedly before and during BNZ. Early on, BNZ reduced C, consisten t with TGF saturation. Over the next 45-60 min, V-LP increased gradual ly by similar to 5 nl/min as C recovered to pre-BNZ levels. BNZ also i ncreased V-LP by similar to 5 nl/min when TGF was rendered inoperative by intratubular wax block, but this increase occurred rapidly. These data demonstrate rightward resetting of TGF during reduced proximal re absorption.