Gastroprotective effect of histamine and acid secretion on ammonia-inducedgastric lesions in rats

Background: Previous studies have shown that ammonia produced by Helicobact er pylori urease or administrated intragastrically exhibits a toxic effect on the gastric mucosa. In the present study we investigated the influence o f histamine and gastric acid secretion on ammonia (NH4OH)-induced gastric l esions. Methods: The gastric mucosa in rats was exposed to NH4OH (1.5 ml of 250 mM solution) under basal conditions, after administration of histamine (1 mg/kg), urea with urease, and ranitidine (40 mg/kg subcutaneously) give n alone or in combination. We measured the area of gastric lesions, gastric blood flow (GBF), plasma gastrin concentration, DNA synthesis, gastric aci d secretion and gastric luminal concentration of PGE(2). Results: Applicati on of NH4OH resulted in the formation of acute gastric lesions. This effect was accompanied by a fall in GBF, a rise in gastric pH, and a reduction in mucosal DNA synthesis. Administration of histamine 30 min prior to NH4OH r educed the area of gastric lesions. This was accompanied by an increase in GBF, DNA synthesis, and prostaglandin E-2 (PGE(2)) production. Ranitidine g iven prior to NH4OH enhanced gastric mucosa damage, and reduced GBF and DNA synthesis. This effect was accompanied by a reduction in gastric acid secr etion. Ranitidine given prior to histamine abolished gastric acid secretion and the protective effect of histamine against NH4OH-induced damage; these effects were accompanied by a decrease in GBF, DNA synthesis, and concentr ation of PGE(2). Pretreatment with 2% urea with urease given prior to NH4OH reduced NH4OH lesions. This effect was associated with an increase in gast ric acid secretion, gastric generation of PGE(2), GBF, and DNA synthesis. R anitidine given prior to urea with urease inhibited gastric acid secretion and the gastroprotective effect of urea-urease gastroprotection. Conclusion s: Histamine and gastric secretion exhibit a protective effect against ammo nia-induced gastric lesions. This effect appears to depend upon the stimula tion of gastric acid secretion and PGE(2) production, and the improvement o f gastric microcirculation.