The potentiation of taurocholate-induced rat gastric erosions following parenteral administration of cyclo-oxygenase inhibitors.
Subcutaneous administration of anti-inflammatory doses of aspirin, indomethacin, naproxen and flurbiprofen inhibited prostacyclin formation ex vivo in the luminally-perfused gastric mucosa of anaesthetized rats. These doses of anti-inflammatory compounds potentiated the formation of gastric mucosal erosions following 3 h luminal perfusion of the topical irritant, acidified sodium taurocholate (2 mM in 100 mM HCl). The increase in luminal acid-loss during gastric perfusion of acidified taurocholate was not significantly enhanced by these anti-inflammatory agents. A correlation was found between the increase in gastric erosion formation and the inhibition of mucosal prostacyclin formation ex vivo by intravenous injection of aspirin or ketoprofen during acid-taurocholate perfusion. BW755C, which failed to inhibit mucosal prostacyclin formation ex vivo, did not significantly augment acid-taurocholate induced gastric damage. The present findings support the potentiating interactions between topical irritation and inhibition of gastric cyclo-oxygenase in the genesis of the gastric lesions.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D001241:Aspirin / Q000633:toxicity; D016861:Cyclooxygenase Inhibitors; D004357:Drug Synergism; D011464:Epoprostenol / Q000096:biosynthesis; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013656:Taurocholic Acid / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D013656:Taurocholic Acid; D011464:Epoprostenol; D001241:Aspirin; D009638:Norepinephrine