Nitric oxide synthase induction and cytoprotection of rat gastric mucosa from injury by ethanol

Publisher Website
Google Scholar
Abstract
The present study determined the effects of nitric oxide (NO) synthase induction on ethanol-mediated damage to rat gastric mucosa. NO synthase activity was determined by [14C]arginine conversion to radiolabeled citrulline. Ca2+-independent NO synthase activity was determined by citrulline formation in the presence of EGTA (1 mM) in the incubation mixture. Intraluminal ethanol administration (2 mL; 40% w/v) to control rats resulted in an increase in mucosal damage characterized as vasocongestion and hemorrhagic necrosis and a reduction in Ca2+-dependent NO synthase activity. Administration of Escherichia coli lipopolysaccharide (LPS; 3 mg/kg i.v.) augmented Ca2+-independent NO synthase activity (determined 4 h later) and reduced damage in response to intraluminal ethanol instillation. Ethanol treatment did not significantly affect induction of NO synthase activity. Dexamethasone pretreatment (1 mg/kg i.v. 2 h before LPS administration) reduced both Ca2+-independent NO synthase activity and the gastroprotective effect of LPS against ethanol-mediated mucosal injury. Likewise, concurrent administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg s.c.) inhibited the gastroprotection associated with LPS treatment, an effect abolished by pretreatment with the NO substrate L-arginine (300 mg/kg s.c.). Indomethacin (5 mg/kg i.v.) was ineffective in suppressing LPS-mediated gastroprotection. These results suggest that while Ca2+-dependent NO formation is inhibited by ethanol treatment, the inducible Ca2+-independent NO synthase plays a role in LPS-mediated gastroprotection against ethanol-mediated damage to the gastric mucosa.Key words: nitric oxide, lipopolysaccharide, ethanol, gastroprotection, dexamethasone.

This publication has 0 references indexed in Scilit: