title: Acute Escherichia coli endotoxaemia decreases the plasma l-arginine/asymmetrical dimethylarginine ratio in humans.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, AKH-Vienna, University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Mittermayer
authors.forename: Khodadad
authors.initials: K
authors.lastname: Namiranian
authors.forename: Johannes
authors.initials: J
authors.lastname: Pleiner
authors.forename: Georg
authors.initials: G
authors.lastname: Schaller
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
mesh_terms: D000208:Acute Disease; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D004311:Double-Blind Method; D019446:Endotoxemia / Q000097:blood*; D004927:Escherichia coli Infections / Q000097:blood* / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
chemical_list: D008070:Lipopolysaccharides; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase