Protective effect of L-arginine against stress-induced gastric mucosal lesions in rats and its relation to nitric oxide-mediated inhibition of neutrophil infiltration.

Pretreatment with l -arginine (150-600 mg kg(-1), i.p.), but not d -arginine (600 mg kg(-1), i.p.), protected against gastric mucosal lesions in rats with water immersion restraint stress over a 6-h period. This protective effect occurred in a dose-dependent manner. Increases in the activities of inducible nitric oxide synthase (iNOS) and myeloperoxidase (MPO), an index of tissue neutrophil infiltration, and the concentration of nitrite/nitrate, breakdown products of nitric oxide, and a decrease in the activity of constitutive nitric oxide synthase (cNOS) occurred in the gastric mucosal tissue with the development of gastric mucosal lesions. The l -arginine pretreatment attenuated the increases in iNOS and MPO activities and nitrite/nitrate concentration and the decrease in cNOS activity in the gastric mucosal tissue in a dose-dependent manner, while the d -arginine pretreatment did not. Both the protective effect of l -arginine (300 mg kg(-1)) against stress-induced gastric mucosal lesions and the attenuating effect of the amino acid on the increases in gastric mucosal iNOS and MPO activities and the decrease in gastric mucosal cNOS activity with the lesion development were counteracted by pretreatment with N(G)-monomethyl- l -arginine (100 mg kg(-1), s.c.), a nitric oxide synthase inhibitor, but not its d -isomer (100 mg kg(-1), s.c.). These results suggest that the protective effect of exogenously administered l -arginine against stress-induced gastric mucosal lesions in rats is, at least in part, due to nitric oxide-mediated inhibition of neutrophil infiltration into the gastric mucosal tissue. Copyright 2001 Academic Press.