RESUMO
Recent research has indicated that nitric oxide [NO] has gastric mucosal protective effects similar to those of prostaglandins [PGs], and that NO and PGs may act synergistically to maintain gastric mucosal integrity. Therefore, the present study aimed at evaluating the anti-ulcer activity of NO and its possible mechanism[s] of action. This was established by investigating the effects of orally administered single and repeated doses of the NO donor sodium nitroprusside [SNP, 3 mg / Kg] or the NO precursor L-arginine [200 mg / Kg] on cold restraint stress-induced and aspirin-induced gastric ulcer in rats, as well as on total gastric acidity in pyloric-ligated rats subjected to stress ulcer. The effects of the H2-receptor antagonist ranitidine also were investigated for comparison. Single and repeated doses of SNP caused a significant decrease in the number [56% and 64%, respectively] and length [51% and 48%, respectively] of gastric lesions in stress-induced ulcer. The protective effect of SNP against ulcer formation was even more marked on aspirin-induced ulcer, causing 71% and 92% decrease in the number, and 62% and 82% decrease in the length of gastric lesions, respectively. Single and repeated doses of L-arginine also were effective in reducing the number and length of gastric lesions in both ulcer models, but to a lesser extent than with SNP. In pyloric-ligated rats, single and repeated doses of SNP or L-arginine caused only moderate reductions in total gastric acidity [27% and 31% for SNP; 20% and 25% for L-arginine, respectively]. Single and repeated doses of ranitidine also produced a significant decrease in the number and length of gastric lesions in both ulcer models, and in total gastric acidity in pyloric-ligated rats. The order of anti-ulcer activity of the three drugs was as follows: Stress-induced ulcer: ranitidine > SNP > L-arginine. Aspirin-induced ulcer: SNP > L-arginine > ranitidine. These results show that NO exerts a significant protective effect against both stress-induced and aspirin-induced ulcer. Inhibition of gastric acid secretion may contribute but is not the only mechanism of the anti-ulcer activity of NO. The results also suggest that concurrent administration of NO donors or L-arginine may be beneficial in prophylaxis against non-steroidal anti-inflammatory drugs [NSAIDs]- induced gastric ulcer