Levcromakalim causes indirect endothelial hyperpolarization via a myo-endothelial pathway

1 Effects of K+ channel opener, levcromakalim, on vascular endothelial cell s were examined. Under voltage- and current-clamp conditions, application o f acetylcholine to dispersed endothelial cells isolated from rabbit superio r mesenteric artery (dispersed RMAECs) produced hyperpolarization and outwa rd currents. On the other hand, dispersed RMAECs did not respond to levcrom akalim. 2 When membrane potential was recorded from endothelium in a mesenteric art erial segment, exposure to levcromakalim in a concentration range of 0.1 to 3 mu M caused concentration-dependent hyperpolarization. The hyperpolariza tion was observed in the absence of external Ca2+ and was inhibited by 10 m u M glibenclamide. 3 The presence of 1 mM heptanol did not affect the levcromakalin-induced hy perpolarization, whereas treatment of the mesenteric arterial segment with 20 mu M 18 beta-glycyrrhetinic acid significantly reduced the hyperpolariza tion. The response to acetylcholine of RMAECs in an arterial segment with 1 8 beta-glycyrrhetinic acid was, however, similar to that without 18 beta-gl ycyrrhetinic acid. 4 These suggest that although RMAECs themselves are functionally insensitiv e to levcromakalim, those in an arterial segment are hyperpolarized by levc romakalim rin myo-endothelial electrical communication.