Inhibition of local nitric oxide synthase increases the homeostatic
efficiency of tubuloglomerular feedback.
Vallon, Volker, and Scott Thomson.
Division of Nephrology-Hypertension, Dept. of Medicine, University
of California San Diego and San Diego Veterans Administration Medical
Center, La Jolla, California 92037
APStracts 2:0106F, 1995.
Nephron filtration rate (SNGFR) and proximal tubular reabsorption are
coordinated by the processes of tubuloglomerular feedback (TGF) and
glomerular tubular balance (GTB). We exam ined 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, or 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.
Received 3 March 1995; accepted in final form 14 June 1995.
APS Manuscript Number F76-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 July 1995.