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

Objective: To study the transported L-arginine in rat hepatocytes during different stages of sepsis. Design: A prospective, controlled study. Subjects: Thirty six Sprague Dawley male rats (250 to 300 g) were anesthetized and studied. Interventions: Early sepsis was produced 9 hrs after cecal ligation and puncture (CLP) and late sepsis developed 18 hrs after CLP. The control group underwent sham operation. Plasma membrane of rat hepatocytes was prepared by differential centrifugation. The [H-3] L-arginine uptake of plasma membrane vesicles during sepsis was measured and inhibition studies employing omega-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine were performed. Measurements and Main Results: L-arginine transport was saturable, increased linearly with plasma membrane protein concentration, and increased with uptake 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 inhibiting L-arginine transport while aminoguanidine was not. Conclusions: L-arginine transport was enhanced in rat hepatocytes during the early stage of sepsis. The increased uptake of L-arginine could contribute to the increase production of nitric oxide by hepatocyte during sepsis.