Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction.
Cell Physiol Biochem
; 42(5): 1802-1811, 2017.
Article
em En
| MEDLINE
| ID: mdl-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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aorta Torácica
/
Endotelina-1
/
Quinazolinonas
/
Dinâmica Mitocondrial
/
Artérias Mesentéricas
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article