Cellular Physiology and Biochemistry (Jul 2017)

Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction

  • Chang Chen,
  • Jin-Lai Gao,
  • Ming-Yu Liu,
  • Shan-Liang Li,
  • Xiu-Chen Xuan,
  • Xin-Zi Zhang,
  • Xi-Yue Zhang,
  • Yuan-Yuan Wei,
  • Chang-Lin Zhen,
  • Jing Jin,
  • Xin Shen,
  • De-Li Dong

DOI
https://doi.org/10.1159/000479536
Journal volume & issue
Vol. 42, no. 5
pp. 1802 – 1811

Abstract

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Background/Aims: Endothelin-1 is implicated in the pathogenesis of hypertension, but the underlying mechanisms remained elusive. Our previous study found that inhibition of mitochondrial fission of smooth muscle cells suppressed phenylephrine- and high K+-induced artery constriction. Here, we studied the effects of mitochondrial fission inhibitors on endothelin-1-induced vasoconstriction. Methods: The tension of rat mesenteric arteries and thoracic aorta was measured by using a multi-wire myograph system. Mitochondrial morphology of aortic smooth muscle cells was observed by using transmission electron microscopy. Results: Dynamin-related protein-1 selective inhibitor mdivi-1 relaxed endothelin-1-induced constriction, and mdivi-1 pre-treatment prevented endothelin-1-induced constriction of rat mesenteric arteries with intact and denuded endothelium. Mdivi-1 had a similar inhibitory effect on rat thoracic aorta. Another mitochondrial fission inhibitor dynasore showed similar effects as mdivi-1 in rat mesenteric arteries. Mdivi-1 inhibited endothelin-1-induced increase of mitochondrial fission in smooth muscle cells of rat aorta. Rho-associated protein kinase inhibitor Y-27632 which relaxed endothelin-1-induced vasoconstriction inhibited endothelin-1-induced mitochondrial fission in smooth muscle cells of rat aorta. Conclusion: Endothelin-1 increases mitochondrial fission in vascular smooth muscle cells, and mitochondrial fission inhibitors suppress endothelin-1-induced vasoconstriction.

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