Jin Jing, Shen Xin, Tai Yu, Li Shanliang, Liu Mingyu, Zhen Changlin, Xuan Xiuchen, Zhang Xiyue, Hu Nan, Zhang Xinzi, Dong Deli
Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China.
Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin Medical University, Harbin 150086, China.
Acta Pharm Sin B. 2017 May;7(3):319-325. doi: 10.1016/j.apsb.2016.12.009. Epub 2017 Mar 3.
Mitochondria are morphologically dynamic organelles which undergo fission and fusion processes. Our previous study found that arterial constriction was always accompanied by increased mitochondrial fission in smooth muscle cells, whereas inhibition of mitochondrial fission in smooth muscle cells was associated with arterial relaxation. Here, we used the typical vasorelaxants, verapamil and phentolamine, to further confirm the coupling between arterial constriction and mitochondrial fission in rat aorta. Results showed that phentolamine but not verapamil induced vasorelaxation in phenylephrine (PE)-induced rat thoracic aorta constriction. Verapamil, but not phentolamine, induced vasorelaxation in high K (KPSS)-induced rat thoracic aorta constriction. Pre-treatment with phentolamine prevented PE- but not KPSS-induced aorta constriction and pre-treatment with verapamil prevented both PE- and KPSS-induced aorta constriction. Transmission electron microscopy (TEM) results showed that verapamil but not phentolamine inhibited KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells, and verapamil prevented both PE- and KPSS-induced excessive mitochondrial fission in aortic smooth muscle cells. Verapamil inhibited KPSS-induced excessive mitochondrial fission in cultured vascular smooth muscle cells (A10). These results further demonstrate that arterial relaxation is coupled to inhibition of mitochondrial fission in arterial smooth muscle cells.
线粒体是形态动态变化的细胞器，会经历分裂和融合过程。我们之前的研究发现，动脉收缩总是伴随着平滑肌细胞中线粒体分裂的增加，而抑制平滑肌细胞中的线粒体分裂则与动脉舒张相关。在此，我们使用典型的血管舒张剂维拉帕米和酚妥拉明，进一步证实大鼠主动脉中动脉收缩与线粒体分裂之间的关联。结果显示，在去甲肾上腺素（PE）诱导的大鼠胸主动脉收缩中，酚妥拉明而非维拉帕米可诱导血管舒张。在高钾（KPSS）诱导的大鼠胸主动脉收缩中，维拉帕米而非酚妥拉明可诱导血管舒张。酚妥拉明预处理可预防PE诱导的而非KPSS诱导的主动脉收缩，维拉帕米预处理可预防PE和KPSS诱导的主动脉收缩。透射电子显微镜（TEM）结果显示，维拉帕米而非酚妥拉明可抑制KPSS诱导的主动脉平滑肌细胞中过度的线粒体分裂，且维拉帕米可预防PE和KPSS诱导的主动脉平滑肌细胞中过度的线粒体分裂。维拉帕米可抑制培养的血管平滑肌细胞（A10）中KPSS诱导的过度线粒体分裂。这些结果进一步证明，动脉舒张与动脉平滑肌细胞中线粒体分裂的抑制相关。
Zotero 插件
