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Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction.

Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction.
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Chen C, Gao JL, Liu MY, Li SL, Xuan XC, Zhang XZ, Zhang XY, Wei YY, Zhen CL, Jin J, Shen X, Dong DL,


Chen C, Gao JL, Liu MY, Li SL, Xuan XC, Zhang XZ, Zhang XY, Wei YY, Zhen CL, Jin J, Shen X, Dong DL, (click to view)

Chen C, Gao JL, Liu MY, Li SL, Xuan XC, Zhang XZ, Zhang XY, Wei YY, Zhen CL, Jin J, Shen X, Dong DL,

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Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2017 07 2742(5) 1802-1811 doi 10.1159/000479536
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.

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