Interrelationship between proximal tubular hydrodynamics and tubuloglomerular feedback in the rat kidney

We have investigated the extent of interaction between the tubuloglomerular feedback mechanism (TGF) and the proximal tubular pressure-mediated changes in glomerular filtration rate (GFR) in hydropenic Wistar rats without interfering with the feedback loop. Infusing or withdrawing tubular fluid at rates up to 5 nl/min from a late proximal site in a free-flowing nephron caused little change in late proximal tubular pressure, implying that GFR varied inversely and proportionately to maintain a constant late proximal flow. By blocking the same tubule and measuring early proximal flow rate during perfusion together with late proximal tubular pressure, we were able to deduce both the feedback curve in the "open-loop" mode and the pressure-flow relationship for the loop of Henle. From these relationships and the free-flow pressure curve, we constructed the feedback curve for the "closed-loop" mode to get the pressure-constant phase. The steady-state operating points lay close to the steepest part of the open-loop curve, suggesting that the feedback normally operates in its most sensitive range. Fluid infusion or withdrawal at rates in excess of 5 nl/min led to nonlinear increases or decreases in intratubular pressure, respectively. It is concluded that for small changes in the loop of Henle inflow around the normal value, TGF operates alone and compensates remarkably accurately. For changes outside this range, concomitant changes in proximal intratubular pressure may reinforce the action of the TGF.