Inhibition of local nitric oxide synthase increases homeostatic efficiency of tubuloglomerular feedback.

Nephron filtration rate (SNGFR) and proximal tubular reabsorption are coordinated by the processes of tubuloglomerular feedback (TGF) and glomerulotubular balance (GTB). We examined the role of nitric oxide (NO) in TGF and GTB, by delivering the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) into late proximal nephrons by micropuncture in Inactin-anesthetized euvolemic rats. First, we determined the dependence of SNGFR on late proximal tubular flow rate (VLP) during orthograde microperfusion of Henle's loop downstream from an obstructing wax block (open-loop microperfusion). Second, we examined the homeostatic efficiency of the TGF-GTB system, (i.e., its ability to stabilize VLP) by perturbing VLP in free-flowing nephrons, while using a noninvasive optical technique to measure flow immediately upstream from the perturbation (closed-loop perturbation). Third, we tested whether L-NMMA could alter the afferent signal to TGF by changing the relationship between VLP and the flow rate (VED) or ionic content (CED) of early distal tubular fluid during open-loop microperfusion. During open-loop microperfusion, L-NMMA decreased SNGFR at VLP between 10 and 40 nl/min but did not alter the relationship between VLP and VED or CED. During closed-loop perturbation, L-NMMA did not affect ambient VLP but increased the homeostatic efficiency of the TGF-GTB system. The combined effects on SNGFR and ambient VLP suggest that L-NMMA reduces proximal reabsorption. However, this could account for only a small fraction of the increase in homeostatic efficiency, the greater share of which must be mediated within the juxtaglomerular apparatus. It appears that juxtaglomerular NO exerts an upward pressure on SNGFR and reduces the efficiency of the TGF-GTB system in stabilizing VLP at ambient flow rates under euvolemic conditions.