On the Mechanisms Underlying Histamine Induction of Gastric Mucosal Lesions in Rats With Partial Gastric Vascular Occlusion

Journal of Pharmacological Sciences

Kikuko Amagase¹  Susumu Okabe¹ 

[1] Department of Applied Pharmacology, Kyoto Pharmaceutical University

关键词: gastric lesion model;    mucosal ischemia;    histamine receptor;    nitric oxide;    prostanoid;   

DOI  :  10.1254/jphs.92.124

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(42)Cited-By(5)Although it is well known that histamine induces gastric mucosal lesions in laboratory animals, the fundamental mechanisms remain unclear. In order to further analyze the vascular mechanisms underlying histamine-induced lesions, a new model was developed in the glandular stomach via administration of histamine (40 mg/kg, s.c.) twice to rats with partial gastric vascular occlusion (ligated left gastric artery and vein) also subjected to pylorus ligation. Both antagonists of histamine H2-receptors (roxatidine and famotidine) and H1-receptors (epinastine and tripelennamine) significantly inhibited lesion formation at doses that did not inhibit acid secretion. Combined treatment of tripelennamine and famotidine synergistically inhibited lesion formation. Nitro L-arginine methyl ester inhibited lesion development; inhibition was reversed by concomitantly administered L-arginine. Indomethacin, diclofenac, and SC-560 (a selective COX-1 inhibitor), but not rofecoxib (a selective COX-2 inhibitor), significantly inhibited lesion formation. In addition, sodium bicarbonate, pirenzepine, S-0509 (a gastrin/CCK2 inhibitor), omeprazole, sucralfate, and a prostaglandin analog also significantly inhibited lesion formation. It was concluded that the mechanism by which histamine induces gastric lesions in rats with partial gastric vascular occlusion appears to involve extensive vasodilation resulting from histamine acting on microvasculature histamine H1- and H2-receptors, generation of endogenous nitric oxide and prostaglandins, with the presence of gastric acid.

【 授权许可】

Unknown