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 in duce gastric ulcer, ET-1 (62.5, 125, 250, and 500 pmol/kg) was injecte d in the submucosal layer of the rat gastric body. Twenty-four hours l ater, gastric ulcer (ulcer area: 10.31 +/-5.13 mm2, mean +/- SE, at 50 0 pmol/kg, n = 8) was induced. The mucosal damage induced by the two h ighest doses was present even at 2 wk after their injection. Measureme nt of the mucosal blood flow at the injected area with three different methods (laser-Doppler flowmetry, hydrogen gas clearance, and reflect ance spectrophotometry) revealed that injected ET- 1 produced an extre mely long-lasting vasoconstriction. Pretreatment with nicardipine, a C a2+-channel blocker (i mg/kg iv), significantly attenuated the ET-1-in duced mucosal damage as well as the decrease in mucosal blood flow. Pr etreatment with omeprazole (5-40 mumol/kg) also, significantly attenua ted the ET-1-induced mucosal damage. Combined pretreatment with omepra zole (40 mumol/kg) and nicardipine almost abolished the ET-1-induced d amage. The present study shows that a novel model for experimental ulc ers can be induced by submucosal injection of ET-1.