Modulation of stress-induced gastric mucosal lesions by exogenous L-arginine

L-arginine, a nitric oxide (NO) precursor, can exert both ameriolative and deteriorative effects on gastric mucosal lesions. This study was designed t o determine whether exogenous L-arginine modulates stress-induced gastric m ucosal lesions through NO production by either constitutive NO synthase (cN OS) or inducible NO synthase (iNOS) in gastric mucosal tissues. In rats sub jected to water immersion restraint stress over a 6-hour period, the concen tration of gastric mucosal nitrite/nitrate, breakdown products of NO, incre ased with the development of gastric mucosal lesions and a decrease in cNOS activity and a drastic increase in iNOS activity in the gastric mucosal ti ssue, Preadministration of L-arginine (150 to 600 mg/kg intraperitoneally) attenuated the lesion development with prevention of increases in gastric m ucosal nitrite/nitrate concentration and iNOS activity. In contrast, postad ministration of L-arginine (150 to 600 mg/kg intraperitoneally) enhanced th e lesion development with further increase in gastric mucosal nitrite/nitra te concentration. This deteriorative action of postadministration of L-argi nine (300 mg/kg intraperitoneally) was prevented by pretreatment with amino guanidine (100 mg/kg subcutaneously), a selective iNOS inhibitor, with inhi bition of increases in gastric mucosal iNOS activity and nitrite/nitrate co ncentration, These results indicate that preadministered L-arginine protect s against water immersion restraint stress-induced gastric mucosal lesions, possibly through restricted NO production by cNOS in gastric mucosal tissu es, whereas postadministered L-arginine aggravates the stress-induced gastr ic mucosal lesions, possibly through excessive NO production by iNOS increa sing in gastric mucosal tissues.