Effect of nitric oxide synthase inhibition on renal hemodynamics in humans: reversal by L-arginine
Wolzt, M.; Schmetterer, L.; Ferber, W.; Artner, E.; Mensik, C.; Eichler, H.G.; Krejcy, K.
American Journal of Physiology 272(2 Pt 2): F178-F182
1997
ISSN/ISBN: 0002-9513 PMID: 9124393 Document Number: 482054
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, N-G-monomethyl-L-arginine (L-NMMA), and a subsequent coinfusion with L-arginine on renal hemodynamics. In a double-blind, randomized crossover design, eight healthy volunteers (means +- 1SD, 25.6 +- 3.1 yr) received a primed constant infusion of L-NMMA (3 mg/kg bolus infusion over 5 min, followed by 50 mu-g cntdot kg-1 cntdot min-1 over 120 min) with subsequent coinfusion Of L-arginine (17 mg cntdot kg-1 cntdot min-1 over 30 min). In the absence of a hypertensive response, L-NMMA decreased renal plasma flow to 79% of baseline (P lt 0.005); this effect was abrogated by L-arginine. Glomerular filtration rate was not affected, NO exhalation was reduced to 30% of baseline (P lt 0.005) by L-NMMA, and 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.