Metoprolol and butoxamine, beta-adrenoceptor antagonists which act selectively at the beta 1- and beta 2-adrenoceptors, respectively, have been investigated for their actions on the ethanol, indomethacin and cold-restraint stress ulcer models. Oral administration of butoxamine but not metoprolol significantly attenuated gastric mucosal damage in the three types of ulcer model. Intraperitoneal injection of butoxamine reduced indomethacin ulceration but not that of the other two models. The stimulatory effect of butoxamine on the gastric mucosal potential difference and intramucosal mucus level correlated positively with its anti-ulcer action. Only oral administration of butoxamine significantly increased the mucosal prostaglandin E2 (PGE2) level but not after intraperitoneal injection. Oral administration of butoxamine also significantly increased the mucosal PGE2 level in the three types of ulcer model but this drug was only effective in the indomethacin ulcer model after intraperitoneal injection. Gastric acid and pepsin output were not affected by either drug. Metoprolol significantly reduced systemic blood pressure; this could be attributed to a reduction in gastric mucosal blood flow. These results imply that beta 2-adrenoceptors play a significant role in the pathogenesis of gastric ulceration. We suggest that the anti-ulcer effect of butoxamine was in part a result of strengthening of the mucosal barrier but that this was not effected by modification of acid or pepsin secretions in the stomach. Stimulation of PGE2 in the gastric mucosa could contribute in part to the anti-ulcer action of the drug, especially when given by the oral route.

Although propranolol has been shown to protect against ethanol and stress ulceration, the antiulcer mechanisms are still unclear. The present study examined the antiulcer mechanisms of propranolol in three different types of ulceration induced respectively by ethanol (60%), indomethacin (30 mg/kg) and stress (cold-restraint). Propranolol pretreatment in the highest dose (10 mg/kg) given either intraperitoneally (i.p.) or orally (p.o.) prevented gastric mucosal damage in these three ulcer models. The three doses of the drug (2.5, 5 or 10 mg/kg) dose-dependently decreased systemic blood pressure which was accompanied by a reduction of gastric mucosal blood flow. These findings suggest that the protection was unrelated to an improvement of local circulation in the stomach. However, propranolol preserved the mucus levels in the three types of ulcer models. The beta-adrenoceptor blocker also increased the basal gastric mucosal potential difference. These findings indicate that propranolol strengthens the mucosal barrier by the preservation of mucosal mucus and enhancement of the mucosal integrity in the stomach.

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