Gastric mucosal protection with chronic mild restraint: role of endogenous prostaglandins

The role of endogenous prostaglandins (PGs) in adaptation of the rat gastric mucosa to chronic stress was examined. After 10 days of chronic mild restraint (CMR), gastric mucosal damage induced by orally administered 40% ethanol was significantly (P less than 0.01) less extensive than that to control mucosae. When the mucosal injury was produced by oral administration of acetylsalicylic acid (250 mg/kg), there was no protection afforded by prior exposure to CMR. Pretreatment with indomethacin (1 mg/kg ip) abolished the protective effects of CMR against ethanol injury. The indomethacin blockade of CMR protection was reversed by the subsequent administration of PGE2 (75 micrograms/kg po). Fundic samples from 10-day CMR rats synthesized three times as much PGE2 (P less than 0.01) and twice as much 6-keto-PGF1alpha (P less than 0.05) as control samples. Thromboxane B2 synthesis by control and CMR samples was not significantly different. The capacity of gastric fundus and antrum to synthesize PGE2 in vitro was higher in samples from CMR rats than from controls. These results suggest that the resistance to gastric injury that develops during chronic stress is mediated by endogenous prostaglandins.