Impaired Adaptive Cytoprotection to Ethanol-Induced Damage in Gastric Mucosa of Portal Hypertensive Rats

Portal hypertension predisposes gastric mucosato increased damage by noxious agents. Adaptivecytoprotection has not been studied in portalhypertensive gastric mucosa. We evaluated adaptivecytoprotection in the gastric mucosa of portal hypertensiverats by exposure to ethanol. The injury index (percentgross lesions) was significantly higher in portalhypertensive rats than in sham-operated rats. The ratio of adaptive cytoprotection, calculated as thedegree of decrease in the injury index caused bypre-absolute-ethanol administration of 20% ethanol, wassignificantly impaired in portal hypertensive rats. Basal levels of gastric mucosal hexosamine werelower in portal hypertensive rats than in controls, anda blunted response to 20% ethanol was associated withportal hypertension. Nitric oxide inhibition (L-NAME, 5 mg/kg) reduced the ratio of adaptivecytoprotection in sham-operated but not in portalhypertensive rats. These results suggest that impairedadaptive cytoprotection in portal hypertensive gastric mucosa may be caused by blunted mucusproduction.