A study of the antiulcer mechanisms of propanolol in rats

Abstract

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.

Different Mechanisms in Formation and Prevention of Indomethacin-induced Gastric Ulcers

“…In an experimental study on rats, Guzel et al showed that fish oil protects stomach tissue from indomethacin-induced ulcers by increasing the mucus secretion of stomach mucosa [67]. Propranolol protects stomach tissue from indomethacin, ethanol, and stressinduced ulcers by preventing the reduction in mucus levels [68]. In addition, rebamipide, a new anti-ulcer drug, has been reported to increase the gastric levels of PGE2 and PGI2, which can increase gastric mucus concentration [69].…”

Study of Propranolol and Its Related Adrenoceptor Antagonists on Changes of Gastric Electrical Parameters Induced by Ethanol in Rats

“…This PD was relatively low as compared with that of our in vivo study [4], suggesting that the tissue may lose some of its viability during preparation and/or the present in vitro conditions may not be completely comparable with in vivo ones. Administration of the ß-adrenoceptor blockers used in the present study did not affect these parameters.…”

“…In anaesthetized animals, transmucosal PD was increased after treatment with ß-adrenoceptor antagonists [4,5]. This elevation of PD was found to be important in the antiulcer action of these drugs in different types of ulceration.…”

“…The present findings also confirm that the ß 2 -adrenoceptor subtype could play a prominent role in this action which is important in the maintenance of the mucosal integrity in the stomach. Previous studies had shown that both propranolol and butoxamine had an antiulcer action in the same organ [4,5]. The preservation of PD in the gastric mucosa would definitely contribute to the protective action of these ß-adrenoceptor blockers.…”

“…These doses have been shown to be effective to reduce gastric mucosal damage in different types of ulceration [4,5,7]. Saline (0.9% w/v, NaCl) was used as the control given by the same route.…”