Chloroquine inhibits vasodilation induced by ATP-sensitive potassium channels in isolated rat aorta

This study examined the effect of chloroquine on vasodilation induced by levcromakalim in isolated endothelium-denuded rat aortas and clarified the underlying mechanisms. We exam-ined the effects of chloroquine, hydroxychloroquine, lipid emulsion, reactive oxygen species (ROS) scavenger N-acetyl-?-cysteine (NAC), and KATP channel inhibitor glibenclamide on levcromakalim-induced vasodilation. The effects of chloroquine, hydroxychloroquine, NAC, and levcromakalim on membrane hyperpolarization and ROS production were examined in aortic vascular smooth muscle cells (VSMCs). Chloroquine inhibited levcromakalim-induced vasodilation more than hydroxychloroquine. NAC attenuated chloroquine-mediated inhibition of levcromakalim-induced vasodilation, while lipid emulsion had no effect. Glibenclamide eliminated levcromakalim-induced vasodilation in aortas pretreated with chloroquine. Chloroquine and hydroxychloroquine inhibited levcromakalim-induced membrane hyperpolarization in VSMCs. Chloroquine and hydroxychloro-quine both produced ROS, but chloroquine produced more. NAC inhibited chloroquine-induced ROS production in VSMCs. Collectively, these results suggest that, partially through ROS production, chloroquine inhibits levcromakalim-induced vasodilation. In addition, chloroquine-induced KATP channel-induced vasodilation impairment was not restored by lipid emulsion.