Department of Pharmacology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, 705-717, Korea.
Vascul Pharmacol. 2013 Sep-Oct;59(3-4):96-102. doi: 10.1016/j.vph.2013.07.007. Epub 2013 Jul 31.
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.
自 Furchgott 和 Zawadzki（1980 年）最初描述以来，已经有许多关于乙酰胆碱（ACh）诱导动脉内皮依赖性舒张的研究。ACh 也产生非内皮依赖性舒张。然而，目前尚不清楚 ACh 诱导的 AMP 激活蛋白激酶（AMPK）激活是否可以减轻去内皮大鼠主动脉的血管收缩。在这里，我们研究了 ACh 是否可以通过 AMPK 激活及其在血管平滑肌细胞（VSMCs）中的潜在机制来调节血管张力。Western blot 显示 ACh 剂量和时间依赖性地增加了 VSMCs 中的 LKB1 和 AMPK 磷酸化。ACh 诱导的 AMPK 激活需要 VSMCs 中的毒蕈碱受体。ACh 诱导的 LKB1 和 AMPK 激活抑制了 VSMCs 中的肌球蛋白轻链激酶（MLCK）和磷酸化肌球蛋白轻链（p-MLC）表达。此外，张力研究显示 ACh 诱导的 AMPK 激活对去内皮大鼠主动脉中苯肾上腺素介导的收缩具有抑制作用。这些数据表明，ACh 诱导的 AMPK 激活可能通过 LKB1-AMPK 依赖性机制减轻去内皮大鼠主动脉的血管收缩。
