Histamine in stress ulcer prophylaxis in rats

Background: Gastrin and its analogues increase the gastric acid secretion, but also enhance mucosal defense mechanisms. On the other hand, increased f ormation of histamine leading to an increase in gastric acid secretion is a ccompanied with gastroprotection and acceleration of gastric ulcer healing. Aim of this study was to examine the effect of histamine on stress induced gastric ulcers in rats. Methods: Male Wistar rats were exposed to water im mersion and restrain stress (WRS) for 3.5 h at 23 degreesC. Before WRS rats were pretreated with saline, histamine, ranitidine or omeprazole. Results: WRS produces gastric lesions which were strongly reduced by ranitidine or omeprazole. Also treatment with histamine markedly reduced ulcer area evoke d by WRS. Addition of histamine to ranitidine or omeprazole caused an addit ional reduction in ulcer area. Gastroprotective effect of histamine was acc ompanied with the increase in gastric blood flow (GBF). Administration of o meprazole or ranitidine alone was without significant effect on GBF. Histam ine caused an slight decrease in gastric luminal pH, whereas ranitidine or omeprazole significantly increased gastric luminal pH. Plasma interleukin-1 beta was significantly reduced after administration of omeprazole, ranitid ine, or histamine, however, the effect of histamine was less pronounced. DN A synthesis was increased after administration of omeprazole, ranitidine or histamine when compared with WRS alone. Administration of histamine in com bination with ranitidine or omeprazole caused an additional increase in DNA synthesis. Conclusions: Histamine exhibits protective effect and increases gastroprotective effect of ranitidine and omeprazole against stress-induce d gastric lesions. This effect of histamine seems to be independent on gast ric acid secretion but related to the increase in gastric blood flow and th e reduction in activation of cytokine cascade.