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An α2-adrenoceptor agonist: Dexmedetomidine induces protective cardiomyocyte hypertrophy through mitochondrial-AMPK pathway

Authors :
Hua Liu
Qianqian Sun
Jianer Du
Cheng Li
Minglu Gu
Yanyifang Xu
Xiaodan Zhang
Xiaojian Weng
Shitong Li
Weiwei Li
Source :
International Journal of Medical Sciences
Publication Year :
2020
Publisher :
Ivyspring International Publisher, 2020.

Abstract

Aims: Dexmedetomidine (Dex) as a highly selective α2-adrenoceptor agonist, was widely used anesthetic in perioperative settings, whether Dex induces cardiac hypertrophy during perioperative administration is unknown. Methods: The effects of Dex on cardiac hypertrophy were explored using the transverse aortic constriction model and neonatal rat cardiomyocytes. Results: We reported that Dex induces cardiomyocyte hypertrophy with activated ERK, AKT, PKC and inactivated AMPK in both wild-type mice and primary cultured rat cardiomyocytes. Additionally, pre-administration of Dex protects against transverse aortic constriction induced-heart failure in mice. We found that Dex up-regulates the activation of ERK, AKT, and PKC via suppression of AMPK activation in rat cardiomyocytes. However, suppression of mitochondrial coupling efficiency and membrane potential by FCCP blocks Dex induced AMPK inactivation as well as ERK, AKT, and PKC activation. All of these effects are blocked by the α2-adrenoceptor antagonist atipamezole. Conclusion: The present study demonstrates Dex preconditioning induces cardiac hypertrophy that protects against heart failure through mitochondria-AMPK pathway in perioperative settings.

Details

Language :
English
ISSN :
14491907
Volume :
17
Issue :
16
Database :
OpenAIRE
Journal :
International Journal of Medical Sciences
Accession number :
edsair.doi.dedup.....9b00b1c96a0e4c53ca7172b1a82cb95e