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Authordc.contributor.authorRiquelme, Jaime 
Authordc.contributor.authorWestermeier, Francisco 
Authordc.contributor.authorHall, Andrew R. 
Authordc.contributor.authorVicencio, Jose 
Authordc.contributor.authorPedrozo Cibils, Zully 
Authordc.contributor.authorIbacache, Mauricio 
Authordc.contributor.authorFuenzalida, Barbara 
Authordc.contributor.authorSobrevia, Luis 
Authordc.contributor.authorDavidson, Sean M. 
Authordc.contributor.authorYellon, Derek M. 
Authordc.contributor.authorSánchez, Gina 
Authordc.contributor.authorLavandero González, Sergio
Admission datedc.date.accessioned2016-06-14T13:31:45Z
Available datedc.date.available2016-06-14T13:31:45Z
Publication datedc.date.issued2016
Cita de ítemdc.identifier.citationPharmacological Research 103 (2016) 318–327en_US
Identifierdc.identifier.otherDOI: 10.1016/j.phrs.2015.11.004
Identifierdc.identifier.urihttp://repositorio.uchile.cl/handle/2250/138791
General notedc.descriptionArtículo de publicación ISIen_US
Abstractdc.description.abstractThe 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 leftventricle 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.en_US
Patrocinadordc.description.sponsorshipFONDECYT 3140532, 1130407, 1150377, 1150887; CONICYT FONDAP 15130011; CONICYT-Chileen_US
Lenguagedc.language.isoenen_US
Publisherdc.publisherElsevieren_US
Type of licensedc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile*
Link to Licensedc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/*
Keywordsdc.subjectDexmedetomidineen_US
Keywordsdc.subjectHearten_US
Keywordsdc.subjecteNOSen_US
Keywordsdc.subjectEndotheliumen_US
Keywordsdc.subjectPreconditioningen_US
Keywordsdc.subjectIschemia-reperfusionen_US
Títulodc.titleDexmedetomidine protects the heart against ischemia-reperfusion injury by an endothelial eNOS/NO dependent mechanismen_US
Document typedc.typeArtículo de revistaen_US


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Atribución-NoComercial-SinDerivadas 3.0 Chile
Except where otherwise noted, this item's license is described as Atribución-NoComercial-SinDerivadas 3.0 Chile