Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition

Cardiac hypertrophy is often associated with an increased sympathetic drive, and both in vitro and in vivo studies have demonstrated the development of cardiomyocyte hypertrophy in response to either α- or β-adrenergic stimulation. Because an association between the Na+/H+ exchanger and cellular gro...

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Autores principales: Ennis, Irene Lucía, Escudero, Eduardo Manuel, Cónsole-Avegliano, Gloria Miriam, Camihort, Gisela, Gómez Dumm, César Leandro Alberto, Seidler, Randolph W., Camilión de Hurtado, María Cristina, Cingolani, Horacio Eugenio
Formato: Articulo
Lenguaje:Inglés
Publicado: 2003
Materias:
Ciencias Médicas
Adrenergic receptor agonists
Antiporters
Fibrosis
Hypertrophy, cardiac
Signal transduction
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/84733
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-84733
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
Adrenergic receptor agonists
Antiporters
Fibrosis
Hypertrophy, cardiac
Signal transduction
spellingShingle Ciencias Médicas
Adrenergic receptor agonists
Antiporters
Fibrosis
Hypertrophy, cardiac
Signal transduction
Ennis, Irene Lucía
Escudero, Eduardo Manuel
Cónsole-Avegliano, Gloria Miriam
Camihort, Gisela
Gómez Dumm, César Leandro Alberto
Seidler, Randolph W.
Camilión de Hurtado, María Cristina
Cingolani, Horacio Eugenio
Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition
topic_facet Ciencias Médicas
Adrenergic receptor agonists
Antiporters
Fibrosis
Hypertrophy, cardiac
Signal transduction
description Cardiac hypertrophy is often associated with an increased sympathetic drive, and both in vitro and in vivo studies have demonstrated the development of cardiomyocyte hypertrophy in response to either α- or β-adrenergic stimulation. Because an association between the Na+/H+ exchanger and cellular growth has been proposed, this study aimed to analyze the possible role of the antiporter in isoproterenol-induced cardiac hypertrophy. Isoproterenol alone (5 mg/kg IP once daily) or combined with a selective inhibitor of the Na+/H+ exchanger activity (3 mg · kg-1 · d-1 BIIB723) was given to male Wistar rats for 30 days. Sex- and age-matched rats that received 0.9% saline IP daily served as controls. Echocardiographic follow-up showed a 33% increase in left ventricular mass in the isoproterenol-treated group, whereas it did not increase in the isoproterenol+BIIB723-treated group. Heart weight-to-body weight ratio at necropsy was 2.44 ± 0.11 in controls and increased to 3.35 ± 0.10 (P < 0.05) with isoproterenol, an effect that was markedly attenuated by BIIB723 (2.82 ± 0.07). Intense cardiomyocyte enlargement and severe subendocardial fibrosis were found in isoproterenol-treated rats, and both effects were attenuated by BIIB723. Myocardial Na+/H+ exchanger activity and protein expression significantly increased in isoproterenol-treated rats compared with the control group (1.45 ± 0.11 vs 0.91 ± 0.05 arbitrary units, P < 0.05). This effect was significantly reduced by BIIB723 (1.17 ± 0.02, P < 0.05). In conclusion, our results show that Na+/H+ exchanger inhibition prevented the development of isoproterenol-induced hypertrophy and fibrosis, providing strong evidence in favor of a key role played by the antiporter in this model of cardiac hypertrophy.
format Articulo
Articulo
author Ennis, Irene Lucía
Escudero, Eduardo Manuel
Cónsole-Avegliano, Gloria Miriam
Camihort, Gisela
Gómez Dumm, César Leandro Alberto
Seidler, Randolph W.
Camilión de Hurtado, María Cristina
Cingolani, Horacio Eugenio
author_facet Ennis, Irene Lucía
Escudero, Eduardo Manuel
Cónsole-Avegliano, Gloria Miriam
Camihort, Gisela
Gómez Dumm, César Leandro Alberto
Seidler, Randolph W.
Camilión de Hurtado, María Cristina
Cingolani, Horacio Eugenio
author_sort Ennis, Irene Lucía
title Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition
title_short Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition
title_full Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition
title_fullStr Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition
title_full_unstemmed Regression of isoproterenol-induced cardiac hypertrophy by Na+/H+ exchanger inhibition
title_sort regression of isoproterenol-induced cardiac hypertrophy by na+/h+ exchanger inhibition
publishDate 2003
url http://sedici.unlp.edu.ar/handle/10915/84733
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