Background and Goal of Study: AMP-activated protein kinase (AMPK) plays an important role in the regulation of vasomotor tone. Propofol induces vasodilation and hypotension in clinical practice. We investigated whether propofol may exert a regulatory effect for vascular tone via AMPK activation and its underlying mechanism in vascular smooth muscle cell (VSMC).
Materials and methods: This study was approved by the Animal Care and Use Committee of Yeungnam University. AMPK and Liver kinase B1 (LKB1) levels using western blot analysis and myosin light-chain kinase (MLCK) and phosphorylated myosin light chain (p-MLC) expression using real-time polymerase chain reaction were measured in primary VSMCs isolated from the thoracic aorta of male Sprague-Dawley rats after propofol treatment. And then we observed whether pharmacological AMPK inhibition with compound C and genetic AMPK inhibition with siRNA transfection can reverse the effect of propofol in VSMCs. Isometric tension response in aortic rings precontracted with phenylephrine was measured after propofol and then pharmacological inhibitor of AMPK, compound C, in endothelium intact and denuded rat aorta. 
Results and discussion: Western blot analysis showed that propofol dose- and time-dependently increased phosphorylation of AMPK and its upstream kinase, LKB1 in VSMCs. LKB1 and AMPK activation by propofol inhibited MLCK and p-MLC expression in VSMCs, which were reversed with treatment of pharmacological AMPK inhibitor, compound C or genetic inhibition of AMPK using siRNA. Isometric tension study showed that propofol-induced AMPK activation attenuated phenylephrine-stimulated contraction in endothelium-denuded rat aorta. 
Conclusions: These data demonstrate for the first time that propofol attenuates phenylephrine-stimulated contraction of rat aortic smooth muscle by inhibition of MLC phosphorylation via activation of LKB1-AMPK in VSMCs. AMPK activation may be another mechanism of propofol-induced vasodilation and hypotension in clinical practice. 
References: 
1. Horman S, Morel N, Vertommen D, Hussain N, Neumann D, Beauloye C, et al. AMP-activated protein kinase phosphorylates and desensitizes smooth muscle myosin light chain kinase. J Biol Chem 2008; 283: 18505-12.
2. Sung JY, Choi HC. Metformin-induced AMP-activated protein kinase activation regulates phenylephrine-mediated contraction of rat aorta. Biochem Biophys Res Commun 2012; 421: 599-604.

Propofol induces vasodilation through AMP-activated protein kinase activation in rat aortic smooth muscle