Effect of nitric oxide synthase inhibition on renal hemodynamics in humans: reversal by L-arginine.
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 microg x kg(-1) x min(-1) over 120 min) with subsequent coinfusion of L-arginine (17 mg x kg(-1) x min(-1) over 30 min). In the absence of a hypertensive response, L-NMMA decreased renal plasma flow to 79% of baseline (P < 0.005); this effect was abrogated by L-arginine. Glomerular filtration rate was not affected, NO exhalation was reduced to 30% of baseline (P < 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.
Wolzt
M
M
Department of Clinical Pharmacology, Vienna University, Austria.
Schmetterer
L
L
Ferber
W
W
Artner
E
E
Mensik
C
C
Eichler
H G
HG
Krejcy
K
K
D000328:Adult; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D012079:Renal Circulation / Q000187:drug effects*; D012119:Respiration; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase