Effects of β-Adrenoceptor Antagonists on Portal Vein Hypertension and Ethanol-induced Gastric Mucosal Damage in Rats

Abstract

The effects of various beta-adrenoceptor antagonists, with different pharmacological properties, on systemic and portal vein blood pressure and on ethanol-induced gastric mucosal damage were examined in surgically-induced portal hypertensive rats. Propranolol (5, 10 or 20 mg kg-1), nadolol (5 or 10 mg kg-1), metoprolol (10 or 20 mg kg-1), labetalol (20 or 40 mg kg-1) and pindolol (3 or 6 mg kg-1) reduced systemic blood pressure to a similar degree in both portal vein-ligated and sham-operated rats. All beta-adrenoceptor antagonists, except for pindolol, significantly reduced portal venous pressure and ethanol-induced macroscopic gastric mucosal damage in portal hypertensive animals. Sham-operated rats had lower portal venous pressure and less gastric damage compared with portal hypertensive rats, but both were unaffected by beta-adrenoceptor antagonist pretreatment. We conclude that: propranolol, nadolol, metoprolol and labetalol are effective in reducing the portal venous pressure and ethanol-induced gastric mucosal damage in portal hypertensive rats, but not in portal normotensive animals; there was no direct relationship between the reduction of portal vein and systemic blood pressure; and local anaesthetic action is probably important in reducing the portal vein pressure and ethanol-induced gastric mucosal lesions, while the intrinsic sympathomimetic effect can counteract the actions of the beta-adrenoceptor antagonists on portal venous pressure and gastric mucosa.

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

“…47 It is conceivable that the effect of glybenclamide in increasing the susceptibility of the gastric mucosa to damage in the PPVL rats is related to its effect on ␤-adrenoceptor function. Antagonist of ␤-adrenoceptor lowers portal pressure 1,10 in rats with PPVL and reduces ethanol-induced gastric mucosal injury. 10 The radioligand binding experiment, however, revealed that glybenclamide did not displace [ 3 H]dihydroalpranolol binding from rat ␤-adrenoceptors.…”

“…Prehepatic portal hypertension was induced by a well-described standard technique. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] An upper midline abdominal incision was made under aseptic conditions. The portal vein was isolated.…”

“…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.…”

“…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.…”

“…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.…”