Acceleration of gastric ulcer healing by omeprazole in portal hypertensive rats. Is its action mediated by gastrin release and the stimulation of epithelial proliferation?

BACKGROUND: Gastric ulcer healing is delayed in patients with portal hypertension (PHT) and often responds poorly to histamine H(2) blockers. Although proton pump inhibitors are more effective anti-ulcer agents, there is little information regarding their efficacy for gastric ulcer in cases of PHT. Therefore, we investigated the effects of a proton pump inhibitor, omeprazole, on the healing of acetic-acid-induced gastric ulcer in PHT rats.

METHODS: Animals studied were 80 male Sprague-Dawley rats aged 7 weeks, of which half underwent two-staged portal vein ligation (PHT rats) and half underwent a sham operation (SO rats). Gastric ulcers were induced by acetic acid. Starting from day 4 after ulcer induction, rats received omeprazole or vehicle orally (50 mg/kg) for 5 or 10 days. Ulcer area, proliferating cell nuclear antigen labelling index (PCNA LI), and serum gastrin levels were recorded.

RESULTS: PHT significantly inhibited epithelial cell proliferation and delayed gastric ulcer healing as indicated by a decreased PCNA LI at the ulcer margin and almost 2-fold larger ulcer area in PHT versus SO rats 14 days after ulcer induction. Ten-day treatment with omeprazole (vs. vehicle) significantly accelerated ulcer healing to a similar extent in both PHT and SO rats. Serum gastrin levels were significantly higher in PHT rats than in SO rats following treatment with omeprazole. Omeprazole (vs. vehicle) restored the decreased PCNA LI at the ulcer margin in PHT rats to that noted in SO rats.

CONCLUSIONS: In PHT rats, omeprazole accelerates gastric ulcer healing, stimulates epithelial cell proliferation at the ulcer margin, and increases serum gastrin levels. Since gastrin is a potent stimulator of gastric epithelial cell proliferation, increased serum gastrin levels may be an important factor in omeprazole-induced stimulation of epithelial cell proliferation and acceleration of gastric ulcer healing in conditions of PHT.