The L-arginine/nitric oxide pathway--biological properties and therapeutic applications.

INTRODUCTION Severe sepsis and trauma are associated with protein catabolism, negative nitrogen balance and immunosuppression and represent a major threat to survival. Nutritional support in these circumstances maintains nitrogen balance and reduces both mortality and morbidity.1-4 However catabolism associated with sepsis is not reversed by standard hyperalimentation formulations.5 There is evidence that individual amino acids, used in pharmacological doses, may modify metabolism and modulate immune function during sepsis. Examples of such amino acids include, leucine, isoleucine and valine (branched chain amino acids) which inhibit muscle protein catabolism,6 glutamine which improves gut immune function7 and arginine which enhances systemic immune function.8 This review will concentrate on the metabolic effects of L-arginine, its significance as a substrate for nitric oxide synthesis and its potential as a pharmacological agent.