Acetylcholine-induced AMP-activated protein kinase activation attenuates vasoconstriction through an LKB1-dependent mechanism in rat aorta.

Numerous studies of acetylcholine (ACh)-induced endothelium-dependent relaxation in arteries have been reported since the original description by Furchgott and Zawadzki (1980). ACh also produces endothelium-independent relaxation. However, it is still unknown whether ACh-induced AMP-activated protein kinase (AMPK) activation can attenuate vasoconstriction in endothelium-denuded rat aorta. Here, we investigated whether ACh may exert a regulatory effect for vascular tone via AMPK activation and its underlying mechanism in vascular smooth muscle cells (VSMCs). Western blotting showed that ACh dose- and time-dependently increased LKB1 and AMPK phosphorylation in VSMCs. The ACh-induced activation of AMPK required muscarinic receptors in VSMCs. LKB1 and AMPK activation by ACh inhibited myosin light-chain kinase (MLCK) and phosphorylated myosin light chain (p-MLC) expression in VSMCs. In addition, a tension study showed the inhibitory effect of ACh-induced AMPK activation on phenylephrine-mediated contraction in endothelium-denuded rat aorta. These data suggest that the ACh-induced activation of AMPK may attenuate vasoconstriction via LKB1-AMPK-dependent mechanism in endothelium-denuded rat aorta.