l-Arginine and nitric oxide synthesis in the cells with inducible NO synthase

The effect of citrulline and ammonium chloride on the nitric oxide formation by peritoneal macrophages and liver tissue cells was studied using ESR spectroscopy. In ex vivo models, the incubation of cells capable of expressing inducible NO synthase (iNOS) with interferon-γ resulted in a moderate increase in the amount of hemoglobin–nitric oxide nitrosyl complexes (Heme–NO NCs), whereas incubation with l-citrulline and ammonium chloride increased the amount of Heme–NO NCs by an order of magnitude. It was assumed that a separate cycle of L-arginine and nitric oxide synthesis exists in the peritoneal macrophages and liver cells, with the major participants of the cycle being the inducible NO synthase enzyme (iNOS) and enzymes that synthesize L-arginine from L-citrulline and a nitrogen source. Functioning of this cycle makes immunocompetent cells with iNOS able to produce NO for a long time and in large amounts.