Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation

Background/Aims: Flow restoration to ischemic myocardium reduces infarct size (IS), but it also promotes reperfusion injury. A burst of reactive oxygen species (ROS) and/or NHE-1 reactivation were proposed to explain this injury. Our study was aimed to shed light on this unresolved issue. Methods: R...

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Autores principales: Garciarena, Carolina Denis, Fantinelli, Juliana Catalina, Caldiz, Claudia Irma, Chiappe de Cingolani, Gladys Ethel, Ennis, Irene Lucía, Pérez, Néstor Gustavo, Cingolani, Horacio Eugenio, Mosca, Susana María
Formato: Articulo
Lenguaje:Inglés
Publicado: 2011
Materias:
Ciencias Médicas
NHE-1
Phosphodiesterase 5A
Reactive oxygen species
Reperfusion injury
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84100
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84100
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
NHE-1
Phosphodiesterase 5A
Reactive oxygen species
Reperfusion injury
spellingShingle Ciencias Médicas
NHE-1
Phosphodiesterase 5A
Reactive oxygen species
Reperfusion injury
Garciarena, Carolina Denis
Fantinelli, Juliana Catalina
Caldiz, Claudia Irma
Chiappe de Cingolani, Gladys Ethel
Ennis, Irene Lucía
Pérez, Néstor Gustavo
Cingolani, Horacio Eugenio
Mosca, Susana María
Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation
topic_facet Ciencias Médicas
NHE-1
Phosphodiesterase 5A
Reactive oxygen species
Reperfusion injury
description Background/Aims: Flow restoration to ischemic myocardium reduces infarct size (IS), but it also promotes reperfusion injury. A burst of reactive oxygen species (ROS) and/or NHE-1 reactivation were proposed to explain this injury. Our study was aimed to shed light on this unresolved issue. Methods: Regional infarction (40 min-ischemia/2 hs-reperfusion) was induced in isolated and perfused rat hearts. Maximal doses of N-(2-mercaptopropionyl)-glycine (MPG 2mmol/L, ROS scavenger), cariporide (10μmol/L, NHE-1 inhibitor), or sildenafil (1μmol/L, phosphodiesterase5A inhibitor) were applied at reperfusion onset. Their effects on IS, myocardial concentration of thiobarbituric acid reactive substances (TBARS), ERK1/2, p90<SUP>RSK</SUP>, and NHE-1 phosphorylation were analyzed. Results: All treatments decreased IS ∼ 50% vs. control. No further protection was obtained by combining cariporide or MPG with sildenafil. Myocardial TBARS increased after infarction and were decreased by MPG or cariporide, but unaffected by sildenafil. In line with the fact that ROS induce MAPK-mediated NHE-1 activation, myocardial infarction increased ERK1/2, p90<SUP>RSK</SUP>, and NHE-1 phosphorylation. MPG and cariporide cancelled these effects. Sildenafil did not reduce the phosphorylated ERK1/2-p90<SUP>RSK</SUP> levels but blunted NHE-1 phosphorylation suggesting a direct dephosphorylating action. Conclusions: 1) Reperfusion injury would result from ROS-triggered MAPK-mediated NHE-1 phosphorylation (and reactivation) during reperfusion; 2) sildenafil protects the myocardium by favouring NHE-1 dephosphorylation and bypassing ROS generation.
format Articulo
Articulo
author Garciarena, Carolina Denis
Fantinelli, Juliana Catalina
Caldiz, Claudia Irma
Chiappe de Cingolani, Gladys Ethel
Ennis, Irene Lucía
Pérez, Néstor Gustavo
Cingolani, Horacio Eugenio
Mosca, Susana María
author_facet Garciarena, Carolina Denis
Fantinelli, Juliana Catalina
Caldiz, Claudia Irma
Chiappe de Cingolani, Gladys Ethel
Ennis, Irene Lucía
Pérez, Néstor Gustavo
Cingolani, Horacio Eugenio
Mosca, Susana María
author_sort Garciarena, Carolina Denis
title Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation
title_short Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation
title_full Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation
title_fullStr Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation
title_full_unstemmed Myocardial reperfusion injury: Reactive oxygen species vs. NHE-1 reactivation
title_sort myocardial reperfusion injury: reactive oxygen species vs. nhe-1 reactivation
publishDate 2011
url http://sedici.unlp.edu.ar/handle/10915/84100
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