Effects of Cimetidine and Omeprazole on Angiogenesis in Granulation Tissue of Acetic Acid-Induced Gastric Ulcers in Rats

Abstract

We investigated the effects of cimetidine and omeprazole on angiogenesis in granulation tissue and on the healing of gastric ulcers induced by acetic acid in rats. Either cimetidine (50 or 100 mg/kg) or omeprazole (10 or 20 mg/kg) was orally administered once daily for 9 consecutive days from the day following ulcer production. The ulcer index on the 10th and 30th days after ulcer production, and the extent of angiogenesis on the 10th day were examined. Cimetidine dose-dependently decreased the extent of angiogenesis on the 10th day, whereas the ulcer index on the 10th days was not significantly different between cimetidine-treated and control rats. The ulcer index of the groups treated with cimetidine during the initial 9-day period was increased compared with the control group on the 30th day. In contrast, oral omeprazole did not affect angiogenesis on the 10th day and decreased the ulcer index on both the 10th and 30th days. These results suggest that oral cimetidine may inhibit angiogenesis in ulcer granulation tissue possibly via the blocking of histamine H₂ receptors and this may be one cause of delayed ulcer healing.