Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism

Riquelme, Jaime A., Westermeier, Francisco, Hall, Andrew R., Vicencio, José Miguel, Pedrozo, Zully, Ibacache, Mauricio, Fuenzalida, Bárbara, Sobrevia, Luis, Davidson, Sean M., Yellon, Derek M., Sanchez, Gina . and Lavandero,Sergio (2016) Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism. Pharmacological Research, 103 318-327. doi:10.1016/j.phrs.2015.11.004

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Author Riquelme, Jaime A.
Westermeier, Francisco
Hall, Andrew R.
Vicencio, José Miguel
Pedrozo, Zully
Ibacache, Mauricio
Fuenzalida, Bárbara
Sobrevia, Luis
Davidson, Sean M.
Yellon, Derek M.
Sanchez, Gina .
Lavandero,Sergio
Title Dexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanism
Journal name Pharmacological Research   Check publisher's open access policy
ISSN 1096-1186
1043-6618
Publication date 2016-01-01
Year available 2015
Sub-type Article (original research)
DOI 10.1016/j.phrs.2015.11.004
Open Access Status File (Author Post-print)
Volume 103
Start page 318
End page 327
Total pages 10
Place of publication London, United Kingdom
Publisher Academic Press
Language eng
Abstract The alpha2-adrenergic receptor agonist Dexmedetomidine (Dex) is a sedative medication used by anesthesiologists. Dex protects the heart against ischemia-reperfusion (IR) and can also act as a preconditioning mimetic. The mechanisms involved in Dex-dependent cardiac preconditioning, and whether this action occurs directly or indirectly on cardiomyocytes, still remain unclear. The endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) signaling pathway and endothelial cells are known to play key roles in cardioprotection against IR injury. Therefore, the aims of this work were to evaluate whether the eNOS/NO pathway mediates the pharmacological cardiac effect of Dex, and whether endothelial cells are required in this cardioprotective action. Isolated adult rat hearts were treated with Dex (10 nM) for 25 min and the dimerization of eNOS and production of NO were measured. Hearts were then subjected to global IR (30/120 min) and the role of the eNOS/NO pathway was evaluated. Dex promoted the activation of eNOS and production of NO. Dex reduced the infarct size and improved the left ventricle function recovery, but this effect was reversed when Dex was co-administered with inhibitors of the eNOS/NO/PKG pathway. In addition, Dex was unable to reduce cell death in isolated adult rat cardiomyocytes subjected to simulated IR. Cardiomyocyte death was attenuated by co-culturing them with endothelial cells pre-treated with Dex. In summary, our results show that Dex triggers cardiac protection by activating the eNOS/NO signaling pathway. This pharmacological effect of Dex requires its interaction with the endothelium.
Keyword Dexmedetomidine
Endothelium
Hearte
Ischemia-reperfusion
NOS
Preconditioning
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Published online 1 December 2015

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2016 Collection
 
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