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Exogenous L ‐arginine attenuates the effects of angiotensin II on renal hemodynamics and the pressure natriuresis–diuresis relationship
Author(s) -
Das Satarupa,
Mattson David L
Publication year - 2014
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12212
Subject(s) - natriuresis , chemistry , endocrinology , medicine , diuresis , angiotensin ii , renal blood flow , renal function , hemodynamics , excretion , urine flow rate , blood pressure
Summary Administration of exogenous L ‐arginine ( L ‐ A rg) attenuates angiotensin‐II ( A ngII)‐mediated hypertension and kidney disease in rats. The present study assessed renal hemodynamics and pressure diuresis–natriuresis in anaesthetized rats infused with vehicle, A ngII (20 ng/kg per min i.v.) or A ngII + L ‐ A rg (300 μ g/kg per min i.v.). Experiments in isolated aortic rings were carried out to assess L ‐ A rg 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, A ngII 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 ‐ A rg reversed the vasoconstrictor effects of A ngII and restored pressure‐dependent diuresis to levels not significantly different from control rats. Dose‐dependent contraction to A ng II (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 A ngII was blunted by 75 ± 3% with 10 −4 mol/L L ‐ A rg. The influence of L ‐ A rg to blunt A ngII‐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 ‐ A rg for cellular uptake, blocked the effect of L ‐ A rg. Anionic amino acids did not influence the effects of L ‐ A rg on A ng II ‐mediated contraction. These studies show that L ‐ A rg blunts A ng II ‐mediated vascular contraction by an endothelial‐ and nitric oxide synthase‐dependent mechanism involving cellular uptake of L ‐ A rg.