Effect of L-lysine on nitric oxide production in ovine endotoxaemia.
Excess production of nitric oxide contributes to the refractory hypotension associated with sepsis and is dependent upon precursor availability, L-arginine. Endothelial uptake of L-arginine by the y+ transporter can be inhibited by another cationic amino acid, L-lysine. This study was undertaken to determine the effects of L-lysine in an anaesthetized ovine model of endotoxaemia in which nitric oxide production is known to be limited by L-arginine availability. The haemodynamic effects of i.v. L-lysine (500 mg kg-1) were compared with those of a known inhibitor of nitric oxide synthase, NG-nitro-L-arginine-methyl ester, L-NAME (25 mg kg-1) and with control animals (n = 6 per group). Serum nitrates, the stable end metabolite of nitric oxide production, were also measured. L-NAME administration caused a significant increase in systemic and pulmonary vascular resistance (P < 0.0001), mean arterial pressure (P < 0.0001) and a reduction in serum nitrate concentrations (P < 0.0001). The administration of L-lysine had no effect on systemic or pulmonary vascular resistance, mean arterial pressure or serum nitrate concentrations. We conclude that the administration of L-lysine does not inhibit nitric oxide production in this model.
Allman
K G
KG
Nuffield Department of Anaesthetics, Radcliffe Infirmary, Oxford.
Stoddart
A P
AP
Young
J D
JD
D000818:Animals; D019446:Endotoxemia / Q000097:blood*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D008239:Lysine / Q000494:pharmacology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012756:Sheep
D004791:Enzyme Inhibitors; D009566:Nitrates; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester