Gastric mucosal barrier of 'in vivo' dogs with a Heidenhain pouch (HP) was broken by butyric acid (BA). Cimetidine intravenously (5 mg/kg/h) prevented HCl secretion. Unidirectional fluxes of H+ and Na+, passive mucosal permeability [evaluated with a low-molecular-weight substance, polyethylenglycole 200(PEG 200)] were increased by BA while transparietal potential difference (PD) was depressed. HCO3- secretion, measured as PCO2 in HP, was incremented . Intragastric perfusion of acetazolamyde (Az) increased loss of BA from HP and enhanced the rupture of gastric mucosa. HCO3- secretion was depressed by Az. Intragastric perfusion of gastric phosphodiesterases inhibitors, theophylline (Th) and 3-isobutyl-1-methylxanthine (IMX), recovered the resistance of gastric mucosa both to ions and PEG 200. Nevertheless HCO3- secretion remained high.
In conclusion: i) cytoprotection of gastric mucosa with either Th or IMX was effective to normalize its resistance to ions and low-molecular-weight substances; ii) increment of HCO3- secretion during cytoprotection was uncoupled with mechanisms dependent on membrane permeability.