Myocardial mineralocorticoid receptor activation by stretching and its functional consequences

Myocardial stretch triggers an angiotensin II-dependent autocrine/paracrine loop of intracellular signals, leading to reactive oxygen species-mediated activation of redox-sensitive kinases. Based on pharmacological strategies, we previously proposed that mineralocorticoid receptor (MR) is necessary...

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Autores principales: Díaz, Romina Gisel, Pérez, Néstor Gustavo, Morgan, Patricio Eduardo, Villa Abrille, María Celeste, Caldiz, Claudia Irma, Nolly, Mariela, Portiansky, Enrique Leo, Ennis, Irene Lucía, Cingolani, Horacio Eugenio
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
Materias:
Ciencias Médicas
Mineralocorticoid receptors
Myocardial stretch
Na+/H+ exchanger
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85165
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-85165
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
Mineralocorticoid receptors
Myocardial stretch
Na+/H+ exchanger
spellingShingle Ciencias Médicas
Mineralocorticoid receptors
Myocardial stretch
Na+/H+ exchanger
Díaz, Romina Gisel
Pérez, Néstor Gustavo
Morgan, Patricio Eduardo
Villa Abrille, María Celeste
Caldiz, Claudia Irma
Nolly, Mariela
Portiansky, Enrique Leo
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Myocardial mineralocorticoid receptor activation by stretching and its functional consequences
topic_facet Ciencias Médicas
Mineralocorticoid receptors
Myocardial stretch
Na+/H+ exchanger
description Myocardial stretch triggers an angiotensin II-dependent autocrine/paracrine loop of intracellular signals, leading to reactive oxygen species-mediated activation of redox-sensitive kinases. Based on pharmacological strategies, we previously proposed that mineralocorticoid receptor (MR) is necessary for this stretch-triggered mechanism. Now, we aimed to test the role of MR after stretch by using a molecular approach to avoid secondary effects of pharmacological MR blockers. Small hairpin interference RNA capable of specifically knocking down the MR was incorporated into a lentiviral vector (l-shMR) and injected into the left ventricular wall of Wistar rats. The same vector but expressing a nonsilencing sequence (scramble) was used as control. Lentivirus propagation through the left ventricle was evidenced by confocal microscopy. Myocardial MR expression, stretch-triggered activation of redox-sensitive kinases (ERK1/2-p90), the consequent Na/H exchanger-mediated changes in pHi (HEPES-buffer), and its mechanical counterpart, the slow force response, were evaluated. Furthermore, reactive oxygen species production in response to a low concentration of angiotensin II (1.0 nmol/L) or an equipotent concentration of epidermal growth factor (0.1 μg/mL) was compared in myocardial tissue slices from both groups. Compared with scramble, animals transduced with l-shMR showed (1) reduced cardiac MR expression, (2) cancellation of angiotensin II-induced reactive oxygen species production but preservation of epidermal growth factor-induced reactive oxygen species production, (3) cancellation of stretch-triggered increase in ERK1/2-p90 phosphorylation, (4) lack of stretch-induced Na/H exchanger activation, and (5) abolishment of the slow force response. Our results provide strong evidence that MR activation occurs after myocardial stretch and is a key factor to promote redox-sensitive kinase activation and their downstream consequences.
format Articulo
Articulo
author Díaz, Romina Gisel
Pérez, Néstor Gustavo
Morgan, Patricio Eduardo
Villa Abrille, María Celeste
Caldiz, Claudia Irma
Nolly, Mariela
Portiansky, Enrique Leo
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
author_facet Díaz, Romina Gisel
Pérez, Néstor Gustavo
Morgan, Patricio Eduardo
Villa Abrille, María Celeste
Caldiz, Claudia Irma
Nolly, Mariela
Portiansky, Enrique Leo
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
author_sort Díaz, Romina Gisel
title Myocardial mineralocorticoid receptor activation by stretching and its functional consequences
title_short Myocardial mineralocorticoid receptor activation by stretching and its functional consequences
title_full Myocardial mineralocorticoid receptor activation by stretching and its functional consequences
title_fullStr Myocardial mineralocorticoid receptor activation by stretching and its functional consequences
title_full_unstemmed Myocardial mineralocorticoid receptor activation by stretching and its functional consequences
title_sort myocardial mineralocorticoid receptor activation by stretching and its functional consequences
publishDate 2014
url http://sedici.unlp.edu.ar/handle/10915/85165
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