The role of the vagus nerve in the protective action of acid inhibitors on ethanol-induced gastric mucosal damage in rats.
The role of vagus in the actions of different acid inhibitors on ethanol-induced gastric damage and mucosal blood flow (GMBF) changes was studied in anaesthetized rats, using an ex vivo stomach chamber preparation. Subdiaphragmatic bilateral vagotomy decreased the basal gastric acid secretion and GMBF; it also intensified ethanol-evoked lesions in the glandular mucosa. Misoprostol, omeprazole and cimetidine produced a similar degree of reduction in acid output. Misoprostol given subcutaneously (s.c.) (50 micrograms/kg), or added to the incubation solution (12.5 micrograms) for 15 min, markedly prevented ethanol-induced lesion formation and reduction in GMBF. The reversing effect of s.c. injection of misoprostol on either lesion formation or on GMBF reduction was attenuated by vagotomy. Omeprazole protected against lesion formation only when present in the incubation solution (12.5 mg) of ex vivo chamber preparations of both vagus-intact and vagotomized animals, but the effect was significantly less in the latter group. The drug also prevented the depressive action of ethanol in vagus-intact animals. Cimetidine pretreatment (50 mg s.c. or 12.5 mg in incubation solution), however, did not modify the effects of ethanol on lesion formation and the GMBF. The findings indicate that the three different types of acid inhibitors exert different actions on ethanol-induced gastric mucosal damage, although they produced similar inhibition of acid output. Vagotomy lowers the GMBF and attenuates the antiulcer action of misoprostol and omeprazole, especially when the drugs are given by the parenteral route.
Cho
C H
CH
Department of Pharmacology, Faculty of Medicine, University of Hong Kong.
Chen
B W
BW
Hui
W M
WM
Lam
S K
SK
Ogle
C W
CW
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D000431:Ethanol / Q000633:toxicity*; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D008297:Male; D016595:Misoprostol / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D014628:Vagotomy; D014630:Vagus Nerve / Q000502:physiology*
D000897:Anti-Ulcer Agents; D016595:Misoprostol; D000431:Ethanol; D002927:Cimetidine; D009853:Omeprazole