Gastroprotective Effect of Histamine and Acid Secretion on Ammonia-Induced Gastric Lesions in Rats

Abstract

Background: Previous studies have shown that ammonia produced by Helicobacter pylori urease or administrated intragastrically exhibits a toxic effect on the gastric mucosa. In the present study we investigated the influence of histamine and gastric acid secretion on ammonia (NH₄OH)-induced gastric lesions. 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) given alone or in combination. We measured the area of gastric lesions, gastric blood flow (GBF), plasma gastrin concentration, DNA synthesis, gastric acid secretion and gastric luminal concentration of PGE₂. Results: Application 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 reduced the area of gastric lesions. This was accompanied by an increase in GBF, DNA synthesis, and prostaglandin E₂ (PGE₂) production. Ranitidine given prior to NH4OH enhanced gastric mucosa damage, and reduced GBF and DNA synthesis. This effect was accompanied by a reduction in gastric acid secretion. 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 concentration of PGE₂. Pretreatment with 2% urea with urease given prior to NH₄OH reduced NH₄OH lesions. This effect was associated with an increase in gastric acid secretion, gastric generation of PGE₂, GBF, and DNA synthesis. Ranitidine given prior to urea with urease inhibited gastric acid secretion and the gastroprotective effect of urea-urease gastroprotection. Conclusions: Histamine and gastric secretion exhibit a protective effect against ammonia-induced gastric lesions. This effect appears to depend upon the stimulation of gastric acid secretion and PGE₂ production, and the improvement of gastric microcirculation.