The indomethacin-induced gastric mucosal damage in rats. Effect of gastric acid, acid inhibition, capsaicin-type agents and prostacyclin.
In pylorus-ligated rats subcutaneous (s.c.) pentagastrin (325.5 nmol/kg) or histamine (54.3 mumol/kg), but not the cholinergic agent bethanechol (7.6 or 15.2 mumol/kg), increased gastric mucosal injury by s.c. indomethacin (55.8 mumol/kg). Intragastric (i.g.) administration of 0.15 or 0.3 N HCl greatly potentiated injury by s.c. indomethacin with widespread ulceration, intragastric bleeding and even perforation. The gastric mucosal damage produced by indomethacin plus 0.3 N HCl was reduced by i.g. capsaicin (3.1-25.1 microM), i.g. resiniferatoxin (0.38-6.1 microM), by s.c. atropine (0.15-1.2 mumol/kg) and to a lesser extent by i.g. prostacyclin (40-267 microM) or s.c. cimetidine (198.2 mumol/kg). The protective effect of capsaicin or resiniferatoxin was not prevented by atropine or cimetidine treatment. Capsaicin (6.5 mM) enhanced gastric injury by s.c. or i.g. indomethacin. Results indicate the importance of early vascular events in the pathogenesis of mucosal injury induced by indomethacin in the stomach and suggest a role for gastric acid in potentiation of such injury. Results further strengthen the idea of a protective role for capsaicin-sensitive sensory nerves in the stomach.
Abdel Salam
O M
OM
First Department of Medicine, Medical University of Pécs, Hungary.
Szolcsányi
J
J
Mózsik
G
G
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002211:Capsaicin / Q000494:pharmacology*; D004224:Diterpenes / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D005744:Gastric Acid / Q000378:metabolism / Q000502:physiology*; D005753:Gastric Mucosa / Q000098:blood supply / Q000473:pathology*; D006632:Histamine / Q000494:pharmacology; D006851:Hydrochloric Acid / Q000494:pharmacology; D007213:Indomethacin; D007545:Isoproterenol / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D009498:Neurotoxins; D014665:Vasodilator Agents; D006632:Histamine; C024353:resiniferatoxin; D011464:Epoprostenol; D010418:Pentagastrin; D007545:Isoproterenol; D006851:Hydrochloric Acid; D002211:Capsaicin; D007213:Indomethacin