Role of histamine in aggravation of gastric acid back-diffusion and vascular permeability in septic rats.

The aim of the present study was to investigate the role of histamine in aggravation of gastric acid back-diffusion and vascular permeability in lipopolysaccharide (LPS)-induced septic rats. Male specific pyrogen-free Wistar rats were deprived food for 24 h before the experiment. Intravenous LPS (3 mg/kg dissolved in sterilized saline) was given to rats 12 h after food removal. Control rats received sterilized saline only. Under diethylether-anesthesia, the pylorus and esophageal sphincters of rats were ligated. Vagotomy also was performed. The stomachs were then irrigated for 3 h with physiological acid solutions containing 0-150 mM HCl plus adequate amount of NaCl. Increases in various ulcerogenic parameters, such as gastric acid back-diffusion, mucosal histamine concentration, luminal hemoglobin (Hb) content and stomach ulcer, were dependent on the concentration of acid solutions irrigated in stomachs of those LPS rats. Gastric vascular permeability also was increased in an acid concentration-related manner. In those LPS rats, high correlation was found between extents of acid back-diffusion and mucosal ulceration. Increased vascular permeability also closely related to the luminal Hb content. Moreover, these ulcerogenic parameters were dose-dependently ameliorated by intraperitoneal ketotifen and ranitidine. Diamine oxidase also was effective in inhibition, but exogenous histamine on the contrary, produced exacerbation of these ulcerogenic parameters. In conclusion, histamine plays a pivotal role in modulating gastric acid back-diffusion and vascular permeability that are greatly associated with hemorrhagic ulcer in septic rats.