INFLUENCE OF ACID AND ANGIOGENESIS ON KINETICS OF GASTRIC-ULCER HEALING IN RATS - INTERACTION WITH INDOMETHACIN

Indomethacin delays healing of experimental gastric ulcers. We investi gated whether inhibition of gastric acid secretion by omeprazole or st imulation of angiogenesis by basic fibroblast growth factor (bFGF) may reverse this delay. Rats with gastric ulcers induced by cryoprobe wer e treated subcutaneously with either placebo, indomethacin (2 x 0.5 mg /kg), bFGF (2 x 100 mu g/kg), omeprazole (1 x 40 mu mol/kg), indometha cin plus omeprazole, or indomethacin plus bFGF given daily for 8, 10, 15, and 22 days. Ulcer size, epithelial cell. proliferation, angiogene sis, and maturation of granulation tissue were sequentially quantified . Omeprazole significantly accelerated ulcer healing in an early phase (days 3-8). In contrast, bFGF accelerated healing in a late phase (da ys 10-15). Indomethacin significantly delayed ulcer healing in late ph ase and decreased prostaglandin generation, cell proliferation, angiog enesis, and maturation of granulation tissue. Despite stimulation of a ngiogenesis, bFGF did not reverse indomethacin-induced delay in ulcer healing. In contrast, omeprazole reversed indomethacin-induced effects on angiogenesis, cell proliferation, maturation of granulation tissue , and ulcer healing rate.