ALTERED CONTROL OF VASCULAR TONE BY ADENOSINE TRIPHOSPHATE-SENSITIVE POTASSIUM CHANNELS IN RATS WITH CIRRHOSIS

Background/Aims: Because the activation of arterial adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels is known to induce vasodilation, these channels may contribute to baseline vasodilator tone in cirrhosis. This study aimed to examine hemodynamic responses to glibenclamide, a K(ATP) channel blocker, and to aprikalim, a vasodilator activating K(ATP) channels, in normal and cirrhotic rats. Methods: Splanchnic and systemic hemodynamic responses to glibenclamide (2.5, 5, 20, 30 mg/kg, intravenously) were studied. The arterial pressure response to aprikalim (200 mu/kg, intravenously) was studied with and without glibenclamide pretreatment (20 mg/kg). Results: In cirrhotic rats, glibenclamide (5, 20, 30 mg/kg but not 2.5 mg/kg) significantly increased vascular resistance in portal and systemic territories. In normal rats, the latter effects occurred with 20 and 30 mg/kg of glibenclamide only. Aprikalim-induced arterial hypotension was significantly less marked in cirrhotic than in normal rats. Following glibenclamide, aprikalim-induced arterial hypotension was significantly less marked in cirrhotic than in normal animals. Conclusions: In rats with cirrhosis, the glibenclamide-induced vasoconstriction indicates that a vasodilator tone due to K(ATP) channel opening existed under baseline conditions. Moreover, this study suggests that the control of vascular tone by K(ATP) channels is altered in cirrhosis.