EFFECT OF L-LYSINE ON NITRIC-OXIDE PRODUCTION IN-OVINE ENDOTOXEMIA

Excess production of nitric oxide contributes to the refractory hypote nsion associated with sepsis and is dependent upon precursor availabil ity, L-arginine. Endothelial uptake of L-arginine by the y(+) transpor ter can be inhibited by another cationic amino acid, L-lysine. This st udy was undertaken to determine the effects of L-lysine in an anaesthe tized ovine model of endotoxaemia in which nitric oxide production is known to be limited by L-arginine availability. The haemodynamic effec ts of i.v. L-lysine (500 mg kg(-1)) were compared with those of a know n inhibitor of nitric oxide synthase, N-G-nitro-L-arginine-methyl este r, L-NAME (25 mg kg(-1)) and with control animals (n=6 per group). Ser um nitrates, the stable end metabolite of nitric oxide production, wer e also measured. L-NAME administration caused a significant increase i n 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 nitrat e concentrations. We conclude that the administration of L-lysine does not inhibit nitric oxide production in this model.