Acute Escherichia coli endotoxaemia decreases the plasma l-arginine/asymmetrical dimethylarginine ratio in humans

Clin Sci (Lond). 2004 Jun;106(6):577-81. doi: 10.1042/CS20030363.


Acute inflammation impairs vascular function. Based on the association between endothelial dysfunction and plasma concentrations of L-arginine and the endogenous nitric oxide synthase inhibitor ADMA (asymmetrical dimethylarginine), we hypothesized that the ratio between L-arginine and ADMA could be affected by experimental inflammation. Plasma concentrations of L-arginine, ADMA and SDMA (symmetrical dimethylarginine) were studied at baseline and 3.5 h after intravenous administration of Escherichia coli endotoxin [LPS (lipopolysaccharide), 20 units/kg of body mass; n =8] or placebo ( n =9) in healthy males. L-Arginine and dimethylarginines were quantified after solid-phase extraction by reversed-phase HPLC. Body temperature, heart rate and leucocyte count increased after LPS administration ( P <0.01 for all). LPS administration decreased plasma concentrations of L-arginine from 66 micromol/l [95% CI (confidence interval): 56, 88] at baseline to 48 micromol/l (CI: 40, 60) after 3.5 h ( P <0.02), but did not affect ADMA and SDMA concentrations. Consequently, the L-arginine/ADMA ratio declined significantly from a median of 159 (CI: 137, 193) to 135 (CI: 103, 146); a decrease of 25 (CI: -68, -13; P <0.02). L-Arginine, ADMA, SDMA and the L-arginine/ADMA ratio remained constant over time in controls. Acute inflammation reduces the L-arginine/ADMA ratio which could contribute to impaired vascular function.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Arginine / analogs & derivatives*
  • Arginine / blood*
  • Blood Pressure / physiology
  • Body Temperature / physiology
  • Double-Blind Method
  • Endotoxemia / blood*
  • Escherichia coli Infections / blood*
  • Escherichia coli Infections / physiopathology
  • Heart Rate / physiology
  • Humans
  • Leukocyte Count
  • Lipopolysaccharides / administration & dosage
  • Male
  • Nitric Oxide Synthase / antagonists & inhibitors


  • Lipopolysaccharides
  • N,N-dimethylarginine
  • Arginine
  • Nitric Oxide Synthase