Gastric ulcer induced by submucosal injection of ET-1: role of potent vasoconstriction and intraluminal acid.
To investigate whether submucosally applied endothelin-1 (ET-1) can induce gastric ulcer, ET-1 (62.5, 125, 250, and 500 pmol/kg) was injected in the submucosal layer of the rat gastric body. Twenty-four hours later, gastric ulcer (ulcer area: 10.31 +/- 5.13 mm2, mean +/- SE, at 500 pmol/kg, n = 8) was induced. The mucosal damage induced by the two highest doses was present even at 2 wk after their injection. Measurement of the mucosal blood flow at the injected area with three different methods (laser-Doppler flowmetry, hydrogen gas clearance, and reflectance spectrophotometry) revealed that injected ET-1 produced an extremely long-lasting vasoconstriction. Pretreatment with nicardipine, a Ca(2+)-channel blocker (1 mg/kg iv), significantly attenuated the ET-1-induced mucosal damage as well as the decrease in mucosal blood flow. Pretreatment with omeprazole (5-40 mumol/kg) also, significantly attenuated the ET-1-induced mucosal damage. Combined pretreatment with omeprazole (40 mumol/kg) and nicardipine almost abolished the ET-1-induced damage. The present study shows that a novel model for experimental ulcers can be induced by submucosal injection of ET-1.
Lazaratos
S
S
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
Kashimura
H
H
Nakahara
A
A
Fukutomi
H
H
Osuga
T
T
Urushidani
T
T
Miyauchi
T
T
Goto
K
K
D000143:Acids / Q000378:metabolism*; D000818:Animals; D004357:Drug Synergism; D016232:Endothelins / Q000008:administration & dosage; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007267:Injections; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013270:Stomach / Q000098:blood supply; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D014661:Vasoconstriction / Q000502:physiology*
D000143:Acids; D016232:Endothelins; D009529:Nicardipine; D009853:Omeprazole