PARADOXICAL EFFECTS OF L-ARGININE ON GASTRIC-MUCOSAL INTEGRITY

Nitric oxide can exert either protective or damaging effects on the ga stric mucosa. To further explore the role of nitric oxide in the modul ation of gastric mucosal defense, the effects of intra-arterial admini stration of the precursor, L-arginine, on susceptibility of the gastri c mucosa to damage induced by topically applied 20% ethanol was examin ed in the rat. L-Arginine administration prior to application of ethan ol produced a dose-dependent increase in the extent of damage (P < 0.0 1 at 300 and P < 0.001 at 500 mg/kg). L-Arginine administration did no t increase the extent of damage at a dose of 300 mg/kg, but did at a d ose of 500 mg/kg. Pretreatment with N-G-nitro-L-arginine-methyl-ester (L-NAME, 25 mg/kg), but not N-G-nitro-D-arginine-methyl-ester (D-NAME, 25 mg/kg) significantly attenuated the exacerbation of injury induced by L-arginine (300 mg/kg). L-Arginine significantly reduced gastric b lood flow relative to controls, while D-arginine had no effect. L-NAME induced a dose-dependent decrease in gastric blood flow and did not a ffect the response to L-arginine. These results suggest that L-arginin e can significantly increase gastric injury through a mechanism that a ppears to be partly nitric oxide-dependent and partly nitric oxide-ind ependent. Changes in gastric blood flow do not appear to be the sole m echanism responsible for the augmentation of injury caused by L-argini ne.