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Exogenous L-arginine attenuates the effects of angiotensin II on renal
hemodynamics and the pressure natriuresis-diuresis relationship
#MMPMID24472006
Das S
; Mattson DL
Clin Exp Pharmacol Physiol
2014[Apr]; 41
(4
): 270-8
PMID24472006
show ga
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
?g/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.