Arginine-nitric oxide pathway in plasma membrane of rat hepatocytes duringearly and late sepsis

Objective: To study the transported L-arginine in rat hepatocytes during di fferent stages of sepsis. Design: A prospective, controlled study. Subjects: Thirty six Sprague Dawley male rats (250 to 300 g) were anestheti zed and studied. Interventions: Early sepsis was produced 9 hrs after cecal ligation and pun cture (CLP) and late sepsis developed 18 hrs after CLP. The control group u nderwent sham operation. Plasma membrane of rat hepatocytes was prepared by differential centrifugation. The [H-3] L-arginine uptake of plasma membran e vesicles during sepsis was measured and inhibition studies employing omeg a-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine were performed. Measurements and Main Results: L-arginine transport was saturable, increase d linearly with plasma membrane protein concentration, and increased with u ptake time up to 5 mins. [H-3] L-arginine uptake increased by 77% to 121% ( p<.05) during early sepsis, with no significant changes during late sepsis. Comparing inhibitors of nitric oxide synthase, L-NAME was effective in inh ibiting L-arginine transport while aminoguanidine was not. Conclusions: L-arginine transport was enhanced in rat hepatocytes during th e early stage of sepsis. The increased uptake of L-arginine could contribut e to the increase production of nitric oxide by hepatocyte during sepsis.