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 to determine whether exogenous L-arginine modulates stress-induced gastric mucosal lesions through NO production by either constitutive NO synthase (cNOS) or inducible NO synthase (iNOS) in gastric mucosal tissues. In rats subjected to water immersion restraint stress over a 6-hour period, the concentration of gastric mucosal nitrite/nitrate, breakdown products of NO, increased with the development of gastric mucosal lesions and a decrease in cNOS activity and a drastic increase in iNOS activity in the gastric mucosal tissue. Preadministration of L-arginine (150 to 600 mg/kg intraperitoneally) attenuated the lesion development with prevention of increases in gastric mucosal nitrite/nitrate concentration and iNOS activity. In contrast, postadministration of L-arginine (150 to 600 mg/kg intraperitoneally) enhanced the lesion development with further increase in gastric mucosal nitrite/nitrate concentration. This deteriorative action of postadministration of L-arginine (300 mg/kg intraperitoneally) was prevented by pretreatment with aminoguanidine (100 mg/kg subcutaneously), a selective iNOS inhibitor, with inhibition of increases in gastric mucosal iNOS activity and nitrite/nitrate concentration. These results indicate that preadministered L-arginine protects against water immersion restraint stress-induced gastric mucosal lesions, possibly through restricted NO production by cNOS in gastric mucosal tissues, whereas postadministered L-arginine aggravates the stress-induced gastric mucosal lesions, possibly through excessive NO production by iNOS increasing in gastric mucosal tissues.
Nishida
K
K
Department of Biochemistry, School of Medicine, Fujita Health University, Aichi, Japan.
Ohta
Y
Y
Ishiguro
I
I
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000097:blood / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological; D017392:Thiobarbituric Acid Reactive Substances; D013997:Time Factors
D006146:Guanidines; D008054:Lipid Peroxides; D009566:Nitrates; D009573:Nitrites; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine