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

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 mumol/l [95 % CI (confidence interval): 56, 88] at baseline to 48 mumol/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.