AJP - Gastrointestinal and Liver Physiology, Vol 265, Issue 3 491-G498, Copyright © 1993 by American Physiological Society
Gastric ulcer induced by submucosal injection of ET-1: role of potent vasoconstriction and intraluminal acid
S. Lazaratos, H. Kashimura, A. Nakahara, H. Fukutomi, T. Osuga, T. Urushidani, T. Miyauchi and K. Goto
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
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.
