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Influences of urethane anesthesia on indomethacin-induced gastric mucosal lesions in rats

Relation to blood glucose levels

  • Esophageal, Gastric, And Duodenal Disorders
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Abstract

Effects of urethane on gastric motility and mucosal ulcerogenic responses induced by indomethacin were investigated in the rat in relation to 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 intraperitoneally did not affect BGL. Subcutaneous administration of indomethacin (25 mg/kg) caused high-amplitude gastric contractions and induced hemorrhagic lesions in the stomachs of conscious rats. These lesions were significantly inhibited by urethane but not pentobarbital. Administration 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 significantly decreased by urethane and increased by pentobarbital. Pretreatment of the animals with yohimbine (5 mg/kg, subcutaneously) but not prazosin (0.5 mg/kg) inhibited the elevation in BGL seen after administration of urethane and allowed resumption both gastric motility and ulcerogenic responses induced by indomethacin, with less change in acid 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 α2-adrenoceptors. These findings also provide further evidence to support the importance of gastric motility in the pathogenesis of these lesions.

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References

  1. Reinert H: Urethane hyperglycemia and hypothalamic activation. Nature 204:889–891, 1964

    PubMed  Google Scholar 

  2. Maggi CA, Meli A: Suitability of urethane anesthesia for physiopharmacological investigations in various systems. Part 1: General considerations. Experientia 42:109–114, 1986

    PubMed  Google Scholar 

  3. Aisaka K, Kitahara T, Koike M, Kuroki M, Ishihara T: Effect of yohimbine on urethane-induced hyperglycemia in rats. Jpn J Pharmacol 49:523–527, 1989

    PubMed  Google Scholar 

  4. Oomura Y, Oyama O, Sugimori M, Nakamura T, Yamada Y: Glucose inhibition of the glucose sensitive neurons in the rat lateral hypothalamus. Nature 247:284–286, 1974

    PubMed  Google Scholar 

  5. Hirano T, Niijima A: Effects of 2-deoxy-d-glucose, glucose, and insulin on efferent activity in gastric vagus nerves. Experientia 36:1197–1200, 1980

    PubMed  Google Scholar 

  6. Mersereau WA, Hinchey EJ: Prevention of phenylbutazone ulcer in the rat by glucose: Role of a glycoprivic receptor system. Am J Physiol 242:G429-G432, 1982

    PubMed  Google Scholar 

  7. Takeuchi K, Ueki S, Okabe S: Importance of gastric motility in the pathogenesis of indomethacin-induced gastric lesions in rats. Dig Dis Sci 31:1114–1121, 1986

    PubMed  Google Scholar 

  8. Okada M, Niida H, Takeuchi K, Okabe S: Role of prostaglandin deficiency in pathogenetic mechanism of gastric lesions induced by indomethacin in rats. Dig Dis Sci 34:694–702, 1989

    PubMed  Google Scholar 

  9. Takeuchi K, Nishiwaki H, Okada M, Niida H, Okabe S: Bilateral adrenalectomy worsens gastric mucosal lesions induced by indomethacin in the rat: Role of enhanced gastric motility. Gastroenterology 97:284–293, 1989

    PubMed  Google Scholar 

  10. Wallace JL, Keenan CM, Granger DN: Gastric ulceration induced by non-steroidal anti-inflammatory drugs is a neutrophil dependent process. Am J Physiol 259:G462-G467, 1990

    PubMed  Google Scholar 

  11. Takeuchi K, Okada M, Niida H, Okabe S: Possible mechanisms involved in gastric hypermotility caused by indomethacin in the rat: Role of glycoprivic response. Dig Dis Sci 35:984–992, 1990

    PubMed  Google Scholar 

  12. Nylander O, Flemstrom G: Effects of alpha-adrenoceptor agonists and antagonists on duodenal surface epithelial HCO 3 secretion in the ratin vivo. Acta Physiol Scand 126:433–441, 1986

    PubMed  Google Scholar 

  13. Takeuchi K, Furukawa O, Tanaka H, Okabe S: A new model of duodenal ulcers induced in rats by indomethacin plus histamine. Gastroenterology 90:636–645, 1986

    PubMed  Google Scholar 

  14. Dunnett CW: A multiple comparison procedure for comparing several treatments with a control. Am J Stat Assoc 50:1096–1121, 1955

    Google Scholar 

  15. Takeuchi K, Ueshima K, Hironaka Y, Fujioka Y, Matsumoto J, Okabe S: Oxygen free radicals and lipid peroxidation in the pathogenesis of gastric mucosal lesions induced by indomethacin in rats: Relation to motility. Digestion 49:175–184, 1991

    PubMed  Google Scholar 

  16. Watanabe K, Yano S, Lin WC: Stimulatory effect of pentobarbital and some anesthetics on gastric secretion in the continuously perfused stomach in rats under urethane anesthesia. Jpn J Pharmacol 44:63–69, 1987

    PubMed  Google Scholar 

  17. Nakadate T, Nakai T, Muraki T, Kato R: Adrenergic regulation of blood glucose levels: Possible involvement of postsynaptic alpha2-type adrenergic receptors regulating insulin release. J Pharmacol Exp Ther 215:226–230, 1980

    PubMed  Google Scholar 

  18. Nakadate T, Nakai T, Muraki T, Kato R: Regulation of plasma insulin level by alpha2-adrenergic receptors. Eur J Pharmacol 65:421–424, 1980

    PubMed  Google Scholar 

  19. Nobuhara Y, Ueki S, Takeuchi K: Influence of prednisolone on gastric alkaline response in rat stomach: A possible explanation for steroid-induced gastric lesion. Dig Dis Sci 30:1167–1173, 1985

    Google Scholar 

  20. Asako H, Kubes P, Wallace J, Gaginella T, Wolf RE, Granger DN: Indomethacin-induced leukocyte adhesion in mesenteric venules: Role of lipoxygenase products. Am J Physiol 262:G903-G908, 1992

    PubMed  Google Scholar 

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Takeuchi, K., Niida, H., Ohuchi, T. et al. Influences of urethane anesthesia on indomethacin-induced gastric mucosal lesions in rats. Digest Dis Sci 39, 2536–2542 (1994). https://doi.org/10.1007/BF02087687

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  • DOI: https://doi.org/10.1007/BF02087687

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