Reduced proximal reabsorption resets tubuloglomerular feedback in euvolemic rats

Inhibition of renal carbonic anhydrase reduces proximal reabsorption and activates tubuloglomerular feedback (TGF). The TGF response is saturable, with highest gain focused near the natural flow rate. Therefore, any large change imposed on ambient tubular flow should reduce the TGF response to subequent flow perturbations. However, TGF tends to align with ambient flow regardless of the rate of ambient flow, suggesting that TGF resets to accommodate changes in flow while maintaining feedback efficiency. We used micropuncture and videometric flow velocitometry to test for TGF resetting in free-flowing nephrons during systemic infusion of the carbonic anhydrase inhibitor benzolamide (BNZ, 5 mg x kg(-1) x h(-1)) in euvolemic rats. Late proximal flow (V(LP)) and the fractional compensation (C) of TGF for perturbations in V(LP) were assessed repeatedly before and during BNZ. Early on, BNZ reduced C, consistent with TGF saturation. Over the next 45-60 min, V(LP) increased gradually by approximately 5 nl/min as C recovered to pre-BNZ levels. BNZ also increased V(LP) by approximately 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 reabsorption.