Exogenous L-arginine attenuates the effects of angiotensin II on renal hemodynamics and the pressure natriuresis-diuresis relationship.
Administration of exogenous L-arginine (L-Arg) attenuates angiotensin-II (AngII)-mediated hypertension and kidney disease in rats. The present study assessed renal hemodynamics and pressure diuresis-natriuresis in anaesthetized rats infused with vehicle, AngII (20 ng/kg per min i.v.) or AngII + L-Arg (300 μg/kg per min i.v.). Experiments in isolated aortic rings were carried out to assess L-Arg effects on the vasculature. Increasing renal perfusion pressure (RPP) from ~100 to 140 mmHg resulted in a nine- to tenfold increase in urine flow and sodium excretion rate in control animals. In comparison, AngII infusion significantly reduced renal blood flow (RBF) and glomerular filtration rate (GFR) by 40-42%, and blunted the pressure-dependent increase in urine flow and sodium excretion rate by 54-58% at elevated RPP. Supplementation of L-Arg reversed the vasoconstrictor effects of AngII and restored pressure-dependent diuresis to levels not significantly different from control rats. Dose-dependent contraction to AngII (10(-10) mol/L to 10(-7) mol/L) was observed with a maximal force equal to 27 ± 3% of the response to 10(-5) mol/L phenylephrine. Contraction to 10(-7) mol/L AngII was blunted by 75 ± 3% with 10(-4) mol/L L-Arg. The influence of L-Arg to blunt AngII-mediated contraction was eliminated by endothelial denudation or incubation with nitric oxide synthase inhibitors. Furthermore, the addition of 10(-3) mol/L cationic or neutral amino acids, which compete with L-Arg for cellular uptake, blocked the effect of L-Arg. Anionic amino acids did not influence the effects of L-Arg on AngII-mediated contraction. These studies show that L-Arg blunts AngII-mediated vascular contraction by an endothelial- and nitric oxide synthase-dependent mechanism involving cellular uptake of L-Arg.
Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Satarupa
S
Das
David L
DL
Mattson
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects* / Q000502:physiology; D005919:Glomerular Filtration Rate; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D012079:Renal Circulation / Q000187:drug effects
D000804:Angiotensin II; D001120:Arginine
L-arginine; blood pressure; nitric oxide; rats