Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium

When the length of the myocardium is increased, a biphasic response to stretch occurs involving an initial rapid increase in force followed by a delayed slow increase called the slow force response (SFR). Confirming previous findings involving angiotensin II in the SFR, it was blunted by AT1 recepto...

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Autores principales: Caldiz, Claudia Irma, Garciarena, Carolina Denis, Dulce, Raúl Ariel, Novaretto, Leonardo P., Yeves, Alejandra del Milagro, Ennis, Irene Lucía, Cingolani, Horacio Eugenio, Chiappe de Cingolani, Gladys Ethel, Pérez, Néstor Gustavo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2007
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/127168
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id I19-R120-10915-127168
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
Internal medicine
Endocrinology
Chemistry
Apocynin
Mitochondrial ROS
NADPH oxidase
Losartan
Angiotensin II
Reactive oxygen species
Intracellular
Potassium channel
spellingShingle Ciencias Médicas
Internal medicine
Endocrinology
Chemistry
Apocynin
Mitochondrial ROS
NADPH oxidase
Losartan
Angiotensin II
Reactive oxygen species
Intracellular
Potassium channel
Caldiz, Claudia Irma
Garciarena, Carolina Denis
Dulce, Raúl Ariel
Novaretto, Leonardo P.
Yeves, Alejandra del Milagro
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Chiappe de Cingolani, Gladys Ethel
Pérez, Néstor Gustavo
Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium
topic_facet Ciencias Médicas
Internal medicine
Endocrinology
Chemistry
Apocynin
Mitochondrial ROS
NADPH oxidase
Losartan
Angiotensin II
Reactive oxygen species
Intracellular
Potassium channel
description When the length of the myocardium is increased, a biphasic response to stretch occurs involving an initial rapid increase in force followed by a delayed slow increase called the slow force response (SFR). Confirming previous findings involving angiotensin II in the SFR, it was blunted by AT1 receptor blockade (losartan). The SFR was accompanied by an increase in reactive oxygen species (ROS) of ∼30% and in intracellular Na+ concentration ([Na⁺]i) of ∼2.5 mmol l⁻¹ over basal detected by H2DCFDA and SBFI fluorescence, respectively. Abolition of ROS by 2-mercapto-propionyl-glycine (MPG) and EUK8 suppressed the increase in [Na⁺]i and the SFR, which were also blunted by Na⁺/H⁺ exchanger (NHE-1) inhibition (HOE642). NADPH oxidase inhibition (apocynin or DPI) or blockade of the ATP-sensitive mitochondrial potassium channels (5HD or glybenclamide) suppressed both the SFR and the increase in [Na⁺]i after stretch, suggesting that endogenous angiotensin II activated NADPH oxidase leading to ROS release by the ATP-sensitive mitochondrial potassium channels, which promoted NHE-1 activation. Supporting the notion of ROS-mediated NHE-1 activation, stretch increased the ERK1/2 and p90rsk kinases phosphorylation, effect that was cancelled by losartan. In agreement, the SFR was cancelled by inhibiting the ERK1/2 signalling pathway with PD98059. Angiotensin II at a dose that mimics the SFR (1 nmol l⁻¹) induced an increase in ·O₂− production of ∼30–40% detected by lucigenin in cardiac slices, an effect that was blunted by losartan, MPG, apocynin, 5HD and glybenclamide. Taken together the data suggest a pivotal role of mitochondrial ROS in the genesis of the SFR to stretch.
format Articulo
Articulo
author Caldiz, Claudia Irma
Garciarena, Carolina Denis
Dulce, Raúl Ariel
Novaretto, Leonardo P.
Yeves, Alejandra del Milagro
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Chiappe de Cingolani, Gladys Ethel
Pérez, Néstor Gustavo
author_facet Caldiz, Claudia Irma
Garciarena, Carolina Denis
Dulce, Raúl Ariel
Novaretto, Leonardo P.
Yeves, Alejandra del Milagro
Ennis, Irene Lucía
Cingolani, Horacio Eugenio
Chiappe de Cingolani, Gladys Ethel
Pérez, Néstor Gustavo
author_sort Caldiz, Claudia Irma
title Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium
title_short Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium
title_full Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium
title_fullStr Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium
title_full_unstemmed Mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium
title_sort mitochondrial reactive oxygen species activate the slow force response to stretch in feline myocardium
publishDate 2007
url http://sedici.unlp.edu.ar/handle/10915/127168
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