Effect of nitric oxide - synthase inhibition on renal hemodynamics
in man: reversal by l-arginine.
Wolzt, Michael, Leopold Schmetterer, Wolfgang Ferber, Erika Artner,
Christa Mensik, Hans-Georg Eichler, Kurt Krejcy.
Department of Clinical Pharmacology, Institute of Medical Physics,
Vienna University, Department of Medical Chemistry and Biochemistry,
University of Innsbruck, Austria
APStracts 3:0181F, 1996.
Animal experiments indicate that inhibition of nitric oxide synthase
(NOS) influences renal hemodynamics and that this effect can be
reversed by L-arginine, the precursor of NO synthesis. We have
therefore studied the effects of an inhibitor of NOS, NG-monomethyl
-L-arginine (L-NMMA), and a subsequent co-infusion with L-arginine on
renal hemodynamics. In a double-blind randomised cross-over design 8
healthy volunteers (mean +/- 1 sd: 25.6 +/- 3.1 yrs.) received a
primed constant infusion of L-NMMA (3 mg kg-1 bolus infusion over 5
min, followed by 50 [mu]g kg-1 min-1 over 120 min) with subsequent
co-infusion of L-arginine (17 mg kg-1 min-1 over 30 min). In the
absence of a hypertensive response L-NMMA decreased RPF to 79% of
baseline (p<0.005), this effect was abrogated by L-arginine.
GFR was not affected, NO exhalation was reduced to 30% of baseline
(p<0.005) by L-NMMA, this effect was attenuated by L-arginine.
Our results demonstrate that basal NO production maintains renal
blood flow in vivo in humans. In addition, the renal vasculature is
particularly sensitive to inhibition of NOS and these pharmacodynamic
effects can be reversed by excess doses of L-arginine.
Received 3 June 1996; accepted in final form 26 September 1996.
APS Manuscript Number F164-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996