Hepatocytes produce nitrogen oxides from L-arginine in response to inflammatory products of Kupffer cells

A metabolic pathway by which L-arginine (L-arg) is converted to the biologically active compound NO· has recently been described in macrophages (M∅) and endothelial cells. This report demonstrates that transferable products from activated Kuppfer cells (KC) induce the conversion of large quantities of L-arg to nitrogen oxides within hepatocytes (HC). In M∅ and endothelial cells, citrulline and NO₂^-/NO₃^- are the stable endproducts of this metabolic pathway. In contrast, HC L-arg metabolism resulted in significantly greater production of NO₂^-/NO₃^- than citrulline. The generation of NO· within HC was associated with a concurrent decrease in total protein synthesis.