Native tubular fluid attenuates ANF-induced inhibition of tubuloglomerular feedback

Abstract

The effect of atrial natriuretic factor [ANF-(1-28); 0.25 microgram.kg-1.min-1] on tubuloglomerular feedback (TGF) and the efficiency of renal blood flow (RBF) autoregulation was determined in anesthetized euvolemic rats. In microperfusion studies, ANF dramatically inhibited (greater than 80%) feedback-mediated decreases in single-nephron glomerular filtration rate (SNGFR) and stop-flow pressure (Psf) when Henle's loop was perfused at 0-48 nl/min with artificial fluid. The sigmoidal relationship between Psf and loop perfusion during control was shifted to a linear relation during ANF; reactivity was almost nonexistent and no inflection point could be discerned. ANF almost completely blocked maximum Psf and SNGFR responses to loop perfusion at rates greater than 24 nl/min. In contrast 30 nl/min loop perfusion with native proximal tubular fluid obtained during ANF infusion restored maximum TGF activity to 70% of control levels. During ANF administration, the paired Psf responses to native and artificial perfusate were significantly different (-5.3 vs. -0.8 mmHg, P less than 0.001), compared with similar responses during control conditions (-7.6 vs. -8.3 mmHg, P greater than 0.1). In free-flow studies, ANF increased proximally and distally measured SNGFR equally. The constancy of the proximal-distal SNGFR difference (10.3 vs. 9.3 nl/min) in the presence of increased distal fluid delivery suggests partial inhibition of TGF during ANF administration. ANF elevated Psf but did not affect basal RBF or the RBF autoregulatory index over an arterial pressure range of 130-70 mmHg. These results indicate that 1) RBF autoregulation is efficiently maintained during ANF infusion when preglomerular vessels are vasodilated and TGF is inhibited by approximately 30%; 2) an endogenous factor(s) in native proximal tubular fluid may attenuate ANF-induced inhibition of TGF; and 3) microperfusion studies using artificial fluid significantly overestimate the net in vivo effect of ANF on TGF.