THE INDOMETHACIN-INDUCED GASTRIC-MUCOSAL DAMAGE IN RATS - EFFECT OF GASTRIC-ACID, ACID INHIBITION, CAPSAICIN-TYPE AGENTS AND PROSTACYCLIN

In pylorus-ligated rats subcutaneous (sc) pentagastrin (325.5 nmol/kg) or histamine (54.3 mu mol/kg), but not the cholinergic agent bethanec hol (7.6 or 15.2 mu mol/kg), increased gastric mucosal injury by sc in domethacin (55.8 mu mol/kg). Intragastric (ig) administration of 0.15 or 0.3 N HCl greatly potentiated injury by sc indomethacin with widesp read ulceration, intragastric bleeding and even perforation. The gastr ic mucosal damage produced by indomethacin plus 0.3 N HCl was reduced by ig capsaicin (3.1-25.1 mu M), ig resiniferatoxin (0.38-6.1 mu M), b y sc atropine (0.15-1.2 mu mol/kg) and to a lesser extent by ig prosta cyclin (40-267 mu M) or sc cimetidine (198.2 mu mol/kg). The protectiv e effect of capsaicin or resiniferatoxin was not prevented by atropine or cimetidine treatment. Capsaicin (6.5 mM) enhanced gastric injury b y sc or ig indomethacin. Results indicate the importance of early vasc ular events in the pathogenesis of mucosal injury induced by indometha cin in the stomach and suggest a role for gastric acid in potentiation of such injury. Results further strengthen the idea of a protective r ole for capsaicin-sensitive sensory nerves in the stomach.