Effects of Selective β-Adrenoceptor Antagonists on Gastric Ulceration in the Rat

Abstract

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.

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

“…Therefore, one should consider that the drugs used in the present study could alter the secretory activity of parietal cells and thereby preserved the decrease of PD induced by ethanol across the gastric mucosa. However, this possibility was unlikely because our previous study reported that using the same doses of the ß-adrenoceptor antagonists did not affect the secretory activity of both acid and pepsin from the stomach [5]. We therefore conclude that the respective preventive action of propranolol, nadolol and butoxamine but not metoprolol and labetalol on gastric transmucosal PD change after ethanol treatment (tables 2-4) is probably due to the protection on the gastric epithelial and glandular cells.…”

“…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.…”

Oral β -stimulants can inhibit passive cutaneous anaphylaxis in rats through an indirect inhibitory mechanism: possible involvement of afferent and efferent nervous system via gastric β 2 -adrenoceptor stimulation

“…The respective doses of l-ephedrine at 15 mg/kg [4], phentolamine at 1 mg/kg [7], propranolol at 1 mg/kg [8], atenolol at 5 mg/kg [8] and butoxamine at 20 mg/kg [9] were used according to or in due consideration of the references and were administered singly or in combination. Reserpine at 1 mg/kg/time was intraperitoneally administered every other day, totally 5 times [10] and the animal was challenged with the antigen on the day 5 after the last administration.…”