Exogenous L-arginine attenuates the effects of angiotensin II on renal hemodynamics and the pressure natriuresis-diuresis relationship

Satarupa Das, David L. Mattson

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)270-278
Number of pages9
JournalClinical and Experimental Pharmacology and Physiology
Volume41
Issue number4
DOIs
StatePublished - Apr 1 2014
Externally publishedYes

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Keywords

  • Blood pressure
  • L-arginine
  • Nitric oxide
  • Rats

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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