We clarified the roles of
histamine H(1)-, H(2)-, H(3)-receptors and oxyradicals in the exacerbation of
acid-induced gastric haemorrhage and
stomach ulcer in endotoxaemic rats by measuring changes in gastric mucosal
glutathione concentrations,
lipid peroxide generation and
histamine levels as well as in
luminal electrolytes and haemoglobin contents.
Stomach ulcers were evaluated by morphological and histological examination. Rats were deprived of food for 24 h, and challenged intravenously with
lipopolysaccharide (LPS, 3 mg/kg) at 0, 12, 18 and 24 h after withdrawal of food. Control rats received saline only. Gastric
truncal vagotomy was performed and followed by irrigation for 3 h with an
acid solution containing 100 mmol/L HC1 and 54 mmol/L NaCl. The augmentation of mucosal permeability to
electrolytes (
acid back-diffusion), haemoglobin contents and
lipid peroxide levels as well as the lowered mucosal
glutathione concentrations were dependent on the duration of LPS intoxication. Serious damage of corpus mucosal cells was observed in
acid-perfused stomachs of LPS rats. Intraperitoneal
diphenhydramine, an H(1)-receptor antagonist, or
ranitidine, an H(2)-receptor blocker, caused dose-dependent inhibition of these ulcerogenic factors.
Antioxidants, including ascorbate and
sodium benzoate, also were effective in inhibition. Moreover, intraperitoneal R-(
alpha)-methylhistamine, an H(3)-receptor agonist, produced elimination, while
thioperamide, an H(3)-receptor antagonist, and exogenous
histamine elevated mucosal
histamine concentrations and haemorrhagic
ulcers in LPS rats. It is concluded that gastric haemorrhage and
stomach ulcers produced by
acid solution in LPS-treated rats are modulated by oxyradicals and
histamine H(1)-, H(2)- and H(3)-receptors.