Potassium channels participate in gastric mucosal protection in rats with partial portal vein ligation

Abstract

Glybenclamide, an adenosine triphosphate-dependent potassium (K ؉ ATP ) channel blocker, lowered portal pressure and attenuated the hyperdynamic splanchnic circulation in rats with partial portal vein ligation (PPVL). The purpose of this report was to confirm these observations and to test the hypothesis that glybenclamide could reduce acidified ethanol-induced gastric mucosal injury in rats with PPVL. Gastric mucosal blood flow (hydrogen gas clearance), systemic blood pressure, and portal pressure were monitored in rats with PPVL or sham operation (SO). Intravenous glybenclamide (20 mg/kg) or vehicle was administered, followed by intragastric acidified ethanol (0.15 N HCl and 15% ethanol). The area of gastric mucosal lesions was assessed by image analysis. In contrast to published findings, there was no significant elevation of portal pressure after glybenclamide administration in rats with PPVL. Glybenclamide did not alter the gastric mucosal hyperemia in these rats. Glybenclamide significantly increased mucosal injury. The data are consistent with the hypothesis that K ؉ ATP channels play a role in protecting the gastric mucosa in rats with PPVL. (HEPATOLOGY 1998;27:1530-1535.)In rats with portal hypertension induced by partial portal vein ligation (PPVL), [1][2][3][4][5][6][7][8][9][10][11][12][13][14] there is an increase in splanchnic blood flow, 1,5,15 including gastric mucosal blood flow. 8,13,16 Reduction of the elevated portal pressure by ␤-adrenoceptor antagonists 1,10 in these rats is associated with a decrease in ethanol-induced gastric mucosal damage. 10 The observation suggests that lowering of the elevated portal pressure may be a marker of decreased susceptibility of the gastric mucosa to noxious damage in rats with PPVL. One report described preliminary data that glybenclamide, an inhibitor of adenosine triphosphate-dependent potassium (K ϩ ATP ) channels, reduced portal pressure, portal tributary blood flow, and hepatic arterial blood flow, and increased portal territory and hepatic arterial vascular resistance in rats with PPVL. 5 The reproducibility of these observations has not been confirmed. If the increased gastric perfusion and elevated portal pressure in rats with PPVL play a role in modulating the susceptibility of the gastric mucosa to noxious damage, attenuation of such changes, as suggested by results of infusing ␤-adrenoceptor antagonist, 10 should lead to a change in the resistance of the mucosa to damage. We tested the hypothesis that glybenclamide, an inhibitor of K ϩ ATP channels, could attenuate gastric mucosal injury produced by intragastric acidified ethanol in rats with PPVL. MATERIALS AND METHODSAnimal Preparation. Male Sprague-Dawley rats weighing 220 to 300 g were kept in a room with controlled temperature of 23°C and humidity. They were fed laboratory rodent diet 5001 (Purina Mills Inc., St. Louis, MO) and tap water. After an overnight fast, rats of comparable weights were randomized to undergo PPVL or sham operation (SO). They were anesthetized with intraperitoneal pe...

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“…The hydrogen gas clearance method has been used in many gastrointestinal studies [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27]. The author's laboratory pioneered the application of this method for assessment of mesenteric adipose tissue blood flow [9].…”