INFLUENCES OF URETHANE ANESTHESIA ON INDOMETHACIN-INDUCED GASTRIC-MUCOSAL LESIONS IN RATS - RELATION TO BLOOD-GLUCOSE LEVELS

Effects of urethane on gastric motility and mucosal ulcerogenic respon ses induced by indomethacin were investigated in the rat in relation t o blood glucose levels (BGL) and compared with those of pentobarbital Na. Urethane (1.25 g/kg) given intraperitoneally, caused a progressive and significant rise in BGL, while pentobarbital (30 mg/kg) given int raperitoneally did not affect BGL. Subcutaneous administration of indo methacin (25 mg/kg) caused high-amplitude gastric contractions and ind uced hemorrhagic lesions in the stomachs. of conscious rats. These les ions were significantly inhibited by urethane but not pentobarbital. A dministration of urethane abolished basal gastric motility and almost completely suppressed the motility responses induced by indomethacin, while pentobarbital did not have much effect on gastric motility under basal and indomethacin-stimulated conditions. Acid secretion was sign ificantly decreased by urethane and increased by pentobarbital. Pretre atment of the animals with yohimbine (5 mg/kg, subcutaneously) but not prazosin (0.5 mg/kg) inhibited the elevation in BGL seen after admini stration of urethane and allowed resumption both gastric motility and ulcerogenic responses induced by indomethacin, with less change in aci d secretion. These results suggest that intraperitoneal administration of urethane prevented indomethacin-induced gastric lesions, probably by inhibiting the enhanced gastric motility response, and this effect may relate to its hyperglycemic action mediated by alpha(2)-adrenocept ors, These findings also provide further evidence to support the impor tance of gastric motility in the pathogenesis of these lesions.