Impaired adaptive cytoprotection to ethanol-induced damage in gastric mucosa of portal hypertensive rats.

Portal hypertension predisposes gastric mucosa to increased damage by noxious agents. Adaptive cytoprotection has not been studied in portal hypertensive gastric mucosa. We evaluated adaptive cytoprotection in the gastric mucosa of portal hypertensive rats by exposure to ethanol. The injury index (percent gross lesions) was significantly higher in portal hypertensive rats than in sham-operated rats. The ratio of adaptive cytoprotection, calculated as the degree of decrease in the injury index caused by pre-absolute-ethanol administration of 20% ethanol, was significantly impaired in portal hypertensive rats. Basal levels of gastric mucosal hexosamine were lower in portal hypertensive rats than in controls, and a blunted response to 20% ethanol was associated with portal hypertension. Nitric oxide inhibition (L-NAME, 5 mg/kg) reduced the ratio of adaptive cytoprotection in sham-operated but not in portal hypertensive rats. These results suggest that impaired adaptive cytoprotection in portal hypertensive gastric mucosa may be caused by blunted mucus production.