On the mechanisms underlying histamine induction of gastric mucosal lesions in rats with partial gastric vascular occlusion.
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 H(2)-receptors (roxatidine and famotidine) and H(1)-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/CCK(2) 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 H(1)- and H(2)-receptors, generation of endogenous nitric oxide and prostaglandins, with the presence of gastric acid.
Amagase
Kikuko
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Yamashina, Kyoto, Japan.
Okabe
Susumu
S
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000473:pathology*; D006632:Histamine / Q000633:toxicity*; D008026:Ligation; D008297:Male; D011708:Pylorus / Q000098:blood supply / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology*; D014652:Vascular Diseases / Q000473:pathology*; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D006632:Histamine