In the present study the vasorelaxing capacity of cromakalim, an ATP-sensitive potassium-channel (K(ATP) channel) activator, and that of levosimendan, a new positive inotropic and vasodilating drug with calcium sensitizing and potassium-channel-activating properties, were compared in human isolated portal vein. Based on the 50% effective concentrations (EC50), levosimendan was found to be about 16-fold more potent (EC50=0.281±0.03 μM) as a relaxing agent than cromakalim (EC50=4.53±0.12 μM) in noradrenaline-precontracted portal venous preparations. Glibenclamide, the known inhibitor of K(ATP) channels, was able to prevent the cromakalim-induced venodilation completely. Glibenclamide (15 μM) decreased the quasi-maximal effect of levosimendan (at 1.27 μM by about 60%) and also the effects of those submicromolar concentrations of the inodilator (at 0.1 μM by 23%, at 0.3 μM by 27% and at 0.7 μM by 19%, on average) which were therapeutically effective in preliminary human studies. These findings indicate that, in the human portal vein, both cromakalim and levosimendan are powerful vasorelaxants and that a considerable part of the relaxing effect induced by levosimendan is of cromakalim type.
ASJC Scopus subject areas
- Pharmaceutical Science