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Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction

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

Cell Physiol Biochem. 2017;42(5):1802-1811.

PMID: 28750371

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP117399947-A	Endothelin 1		117399-94-7	Price

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