ADAPTATION OF RAT GASTRIC-MUCOSA TO ASPIRIN REQUIRES MUCOSAL CONTACT

Adaptation of the gastric mucosa to repeated administration of aspirin is a well-documented phenomenon, but the underlying mechanism is not fully understood. In this study, we tested the hypothesis that adaptat ion of the rat stomach to chronic aspirin administration required cont act between the aspirin and the gastric mucosa. Rats were orally treat ed twice daily with either aspirin (100 mg/kg) or the vehicle. After v arious periods of treatment less than or equal to 20 days), the rats w ere given a higher dose of aspirin (250 mg/kg po), and the extent of g astric damage was assessed 3 h later. Rats receiving chronic aspirin d emonstrated the development, in a time-dependent manner, of resistance to the damaging effects of aspirin. Chronic aspirin administration al so significantly decreased the susceptibility of the rat stomach to da mage induced by indomethacin or naproxen. The adaptation phenomenon wa s associated with a parallel increase in inflammatory infiltration of the mucosa, as measured by tissue myeloperoxidase activity and histolo gy. Prostaglandin synthesis was markedly suppressed (>80%) in all rats treated with aspirin. Gastric mucosal ornithine decarboxylase activit y was not affected by chronic aspirin administration. If aspirin was a dministered subcutaneously or intrajejunally for 20 days, neither adap tation nor inflammation of the gastric mucosa was observed. These stud ies demonstrate that the rat stomach adapts to chronic oral administra tion of aspirin, but not to aspirin administration via other routes. A daptation of the gastric mucosa occurred in parallel to infiltration o f granulocytes. Whether these two phenomena are mechanistically or cau sally linked is not yet clear.