Role of prostaglandins generated by cyclooxygenase-1 and cyclooxygenase-2 in healing of ischemia-reperfusion-induced gastric lesions

In this study, ischemia-reperfusion produced in rats by clamping the celiac artery for 0.5 h followed by 1 h of reperfusion was used to develop a new model of superficial gastric erosions progressing to deeper ulcers. Ischemi a alone resulted in an immediate fall in gastric blood flow but no gross mu cosal lesions were observed. When ischemia was followed by reperfusion, gas tric erosive lesions occurred, reached a maximum at 12 h and then declined after 24 h. These acute erosions progressed into deeper lesions 24 h after ischemia-reperfusion and reached a peak after 3 days. Gastric blood flow an d the mucosal generation of prostaglandin E-2 were significantly suppressed immediately following ischemia-reperfusion, but with the healing of deeper gastric ulcers, both gastric blood flow and prostaglandin El generation we re gradually restored. Cyclooxygenase-l mRNA was detected by reverse transc ription-polymerase chain reaction in intact gastric mucosa and throughout t he recovery of the mucosa from acute ischemia-reperfusion lesions, whereas cyclooxygenase-2 mRNA, was recorded only after ischemia-reperfusion. NS-398 and rofecoxib, selective inhibitors of cyclooxyganase-2, failed to affect prostaglandin E-2 generation in the non-ulcerated gastric mucosa but inhibi ted it significantly in the ulcer area. The two cyclooxygenase-2 inhibitors as well as resveratrol, a specific cyclooxygenase-l inhibitor and indometh acin and meloxicam, non-specific inhibitors of cyclooxygenase, augmented ac ute gastric erosions induced by ischemia-reperfusion and delayed significan tly the progression of these lesions into deeper ulcers at each time interv al after ischemia-reperfusion. We conclude that prostaglandins generated by both cyclooxygenase-l and cyclooxygenase-2. contribute to the healing of g astric lesions induced by ischemia-reperfusion. (C) 1999 Elsevier Science B .V. All rights reserved.