Interactive roles of endogenous prostaglandin and nitric oxide in regulation of acid secretion by damaged rat stomachs

Background: The acid inhibitory mechanism in the damaged stomach is known t o involve endogenous nitric oxide (NO) as well as prostaglandin (PG). Aim: To investigate the interaction between PG and NO in regulation of acid secretion in the stomach following damage. Methods: Under urethane anaesthesia, a rat stomach was mounted in an ex viv o chamber and perfused with saline. Acid secretion, luminal PGE(2), NO meta bolites (NOx) and histamine output were measured before and after applicati on of 20 mM taurocholate Na (TC) for 30 min, with or without pre-treatment with indomethacin and/or N-G-nitro-L-arginine methyl ester (L-NAME). Results: Exposure of the stomach to TC caused a decrease in acid secretion, with concomitant increase of both luminal NOx and PGE(2). Either L-NAME or indomethacin reduced the decrease in acid secretion in response to TC, but only L-NAME allowed acid secretion to increase over basal values. L-NAME p revented the increase of luminal NOx after TC treatment, while indomethacin inhibited PGE(2) release during and after exposure to TC. The increase in acid secretion in the presence of L-NAME was prevented when indomethacin wa s given concomitantly. TC treatment increased histamine output in the lumen , a process that was enhanced by L-NAME but reduced by indomethacin. Conclusions: Damage to the stomach increases both NO and PG in the lumen, a nd decreases acid secretion. Inhibiting NO production increases acid secret ion in the damaged stomach, but only when PG biosynthesis is intact. It is assumed that endogenous PG has a dual role in the regulation of acid secret ion in the damaged stomach: an inhibitory effect at the parietal cell and a n excitatory effect probably through enhancing the release of mucosal hista mine.