The Anrep effect requires transactivation of the epidermal growth factor receptor
- Autores
- Villa Abrille, María Celeste; Caldiz, Claudia Irma; Ennis, Irene Lucía; Nolly, Mariela; Casarini, María Jesús; Chiappe de Cingolani, Gladys Ethel; Cingolani, Horacio Eugenio; Pérez, Néstor Gustavo
- Año de publicación
- 2010
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Myocardial stretch elicits a biphasic contractile response: the Frank-Starling mechanism followed by the slow force response (SFR) or Anrep effect. In this study we hypothesized that the SFR depends on epidermal growth factor receptor (EGFR) transactivation after the myocardial stretch-induced angiotensin II (Ang II)/endothelin (ET) release. Experiments were performed in isolated cat papillary muscles stretched from 92 to 98% of the length at which maximal twitch force was developed (Lmax). The SFR was 123 ± 1% of the immediate rapid phase (n = 6, P < 0.05) and was blunted by preventing EGFR transactivation with the Src-kinase inhibitor PP1 (99 ± 2%, n = 4), matrix metalloproteinase inhibitor MMPI (108 ± 4%, n = 11), the EGFR blocker AG1478 (98 ± 2%, n = 6) or the mitochondrial transition pore blocker clyclosporine (99 ± 3%, n = 6). Stretch increased ERK1/2 phosphorylation by 196 ± 17% of control (n = 7, P < 0.05), an effect that was prevented by PP1 (124 ± 22%, n = 7) and AG1478 (131 ± 17%, n = 4). In myocardial slices, Ang II (which enhances ET mRNA) or endothelin-1 (ET-1)-induced increase in O2- production (146 ± 14%, n = 9, and 191 ± 17%, n = 13, of control, respectively, P < 0.05) was cancelled by AG1478 (94 ± 5%, n = 12, and 98 ± 15%, n = 8, respectively) or PP1 (100 ± 4%, n = 6, and 99 ± 8%, n = 3, respectively). EGF increased O2- production by 149 ± 4% of control (n = 9, P < 0.05), an effect cancelled by inhibiting NADPH oxidase with apocynin (110 ± 6% n = 7), mKATP channels with 5-hydroxydecanoic acid (5-HD; 105 ± 5%, n = 8), the respiratory chain with rotenone (110 ± 7%, n = 7) or the mitochondrial permeability transition pore with cyclosporine (111 ± 10%, n = 6). EGF increased ERK1/2 phosphorylation (136 ± 8% of control, n = 9, P < 0.05), which was blunted by 5-HD (97 ± 5%, n = 4), suggesting that ERK1/2 activation is downstream of mitochondrial oxidative stress. Finally, stretch increased Ser703 Na+/H+ exchanger-1 (NHE-1) phosphorylation by 172 ± 24% of control (n = 4, P < 0.05), an effect that was cancelled by AG1478 (94 ± 17%, n = 4). In conclusion, our data show for the first time that EGFR transactivation is crucial in the chain of events leading to the Anrep effect.
Facultad de Ciencias Médicas - Materia
-
Ciencias Médicas
Angiotensin II
Animals
Cats
Endothelin-1
Extracellular Signal-Regulated MAP Kinases
Mechanoreceptors
Myocardial Contraction
Oxidation-Reduction
Papillary Muscles
Phosphorylation
Reactive Oxygen Species
Receptor Cross-Talk
Receptors, G-Protein-Coupled
Reverse Transcriptase Polymerase Chain Reaction
RNA - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by-nc-sa/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/82420
Ver los metadatos del registro completo
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The Anrep effect requires transactivation of the epidermal growth factor receptorVilla Abrille, María CelesteCaldiz, Claudia IrmaEnnis, Irene LucíaNolly, MarielaCasarini, María JesúsChiappe de Cingolani, Gladys EthelCingolani, Horacio EugenioPérez, Néstor GustavoCiencias MédicasAngiotensin IIAnimalsCatsEndothelin-1Extracellular Signal-Regulated MAP KinasesMechanoreceptorsMyocardial ContractionOxidation-ReductionPapillary MusclesPhosphorylationReactive Oxygen SpeciesReceptor Cross-TalkReceptors, G-Protein-CoupledReverse Transcriptase Polymerase Chain ReactionRNAMyocardial stretch elicits a biphasic contractile response: the Frank-Starling mechanism followed by the slow force response (SFR) or Anrep effect. In this study we hypothesized that the SFR depends on epidermal growth factor receptor (EGFR) transactivation after the myocardial stretch-induced angiotensin II (Ang II)/endothelin (ET) release. Experiments were performed in isolated cat papillary muscles stretched from 92 to 98% of the length at which maximal twitch force was developed (Lmax). The SFR was 123 ± 1% of the immediate rapid phase (n = 6, P < 0.05) and was blunted by preventing EGFR transactivation with the Src-kinase inhibitor PP1 (99 ± 2%, n = 4), matrix metalloproteinase inhibitor MMPI (108 ± 4%, n = 11), the EGFR blocker AG1478 (98 ± 2%, n = 6) or the mitochondrial transition pore blocker clyclosporine (99 ± 3%, n = 6). Stretch increased ERK1/2 phosphorylation by 196 ± 17% of control (n = 7, P < 0.05), an effect that was prevented by PP1 (124 ± 22%, n = 7) and AG1478 (131 ± 17%, n = 4). In myocardial slices, Ang II (which enhances ET mRNA) or endothelin-1 (ET-1)-induced increase in O2- production (146 ± 14%, n = 9, and 191 ± 17%, n = 13, of control, respectively, P < 0.05) was cancelled by AG1478 (94 ± 5%, n = 12, and 98 ± 15%, n = 8, respectively) or PP1 (100 ± 4%, n = 6, and 99 ± 8%, n = 3, respectively). EGF increased O2- production by 149 ± 4% of control (n = 9, P < 0.05), an effect cancelled by inhibiting NADPH oxidase with apocynin (110 ± 6% n = 7), mKATP channels with 5-hydroxydecanoic acid (5-HD; 105 ± 5%, n = 8), the respiratory chain with rotenone (110 ± 7%, n = 7) or the mitochondrial permeability transition pore with cyclosporine (111 ± 10%, n = 6). EGF increased ERK1/2 phosphorylation (136 ± 8% of control, n = 9, P < 0.05), which was blunted by 5-HD (97 ± 5%, n = 4), suggesting that ERK1/2 activation is downstream of mitochondrial oxidative stress. Finally, stretch increased Ser703 Na+/H+ exchanger-1 (NHE-1) phosphorylation by 172 ± 24% of control (n = 4, P < 0.05), an effect that was cancelled by AG1478 (94 ± 17%, n = 4). In conclusion, our data show for the first time that EGFR transactivation is crucial in the chain of events leading to the Anrep effect.Facultad de Ciencias Médicas2010info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf1579-1590http://sedici.unlp.edu.ar/handle/10915/82420enginfo:eu-repo/semantics/altIdentifier/issn/0022-3751info:eu-repo/semantics/altIdentifier/doi/10.1113/jphysiol.2009.186619info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:15:31Zoai:sedici.unlp.edu.ar:10915/82420Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:15:31.347SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
title |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
spellingShingle |
The Anrep effect requires transactivation of the epidermal growth factor receptor Villa Abrille, María Celeste Ciencias Médicas Angiotensin II Animals Cats Endothelin-1 Extracellular Signal-Regulated MAP Kinases Mechanoreceptors Myocardial Contraction Oxidation-Reduction Papillary Muscles Phosphorylation Reactive Oxygen Species Receptor Cross-Talk Receptors, G-Protein-Coupled Reverse Transcriptase Polymerase Chain Reaction RNA |
title_short |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
title_full |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
title_fullStr |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
title_full_unstemmed |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
title_sort |
The Anrep effect requires transactivation of the epidermal growth factor receptor |
dc.creator.none.fl_str_mv |
Villa Abrille, María Celeste Caldiz, Claudia Irma Ennis, Irene Lucía Nolly, Mariela Casarini, María Jesús Chiappe de Cingolani, Gladys Ethel Cingolani, Horacio Eugenio Pérez, Néstor Gustavo |
author |
Villa Abrille, María Celeste |
author_facet |
Villa Abrille, María Celeste Caldiz, Claudia Irma Ennis, Irene Lucía Nolly, Mariela Casarini, María Jesús Chiappe de Cingolani, Gladys Ethel Cingolani, Horacio Eugenio Pérez, Néstor Gustavo |
author_role |
author |
author2 |
Caldiz, Claudia Irma Ennis, Irene Lucía Nolly, Mariela Casarini, María Jesús Chiappe de Cingolani, Gladys Ethel Cingolani, Horacio Eugenio Pérez, Néstor Gustavo |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Ciencias Médicas Angiotensin II Animals Cats Endothelin-1 Extracellular Signal-Regulated MAP Kinases Mechanoreceptors Myocardial Contraction Oxidation-Reduction Papillary Muscles Phosphorylation Reactive Oxygen Species Receptor Cross-Talk Receptors, G-Protein-Coupled Reverse Transcriptase Polymerase Chain Reaction RNA |
topic |
Ciencias Médicas Angiotensin II Animals Cats Endothelin-1 Extracellular Signal-Regulated MAP Kinases Mechanoreceptors Myocardial Contraction Oxidation-Reduction Papillary Muscles Phosphorylation Reactive Oxygen Species Receptor Cross-Talk Receptors, G-Protein-Coupled Reverse Transcriptase Polymerase Chain Reaction RNA |
dc.description.none.fl_txt_mv |
Myocardial stretch elicits a biphasic contractile response: the Frank-Starling mechanism followed by the slow force response (SFR) or Anrep effect. In this study we hypothesized that the SFR depends on epidermal growth factor receptor (EGFR) transactivation after the myocardial stretch-induced angiotensin II (Ang II)/endothelin (ET) release. Experiments were performed in isolated cat papillary muscles stretched from 92 to 98% of the length at which maximal twitch force was developed (Lmax). The SFR was 123 ± 1% of the immediate rapid phase (n = 6, P < 0.05) and was blunted by preventing EGFR transactivation with the Src-kinase inhibitor PP1 (99 ± 2%, n = 4), matrix metalloproteinase inhibitor MMPI (108 ± 4%, n = 11), the EGFR blocker AG1478 (98 ± 2%, n = 6) or the mitochondrial transition pore blocker clyclosporine (99 ± 3%, n = 6). Stretch increased ERK1/2 phosphorylation by 196 ± 17% of control (n = 7, P < 0.05), an effect that was prevented by PP1 (124 ± 22%, n = 7) and AG1478 (131 ± 17%, n = 4). In myocardial slices, Ang II (which enhances ET mRNA) or endothelin-1 (ET-1)-induced increase in O2- production (146 ± 14%, n = 9, and 191 ± 17%, n = 13, of control, respectively, P < 0.05) was cancelled by AG1478 (94 ± 5%, n = 12, and 98 ± 15%, n = 8, respectively) or PP1 (100 ± 4%, n = 6, and 99 ± 8%, n = 3, respectively). EGF increased O2- production by 149 ± 4% of control (n = 9, P < 0.05), an effect cancelled by inhibiting NADPH oxidase with apocynin (110 ± 6% n = 7), mKATP channels with 5-hydroxydecanoic acid (5-HD; 105 ± 5%, n = 8), the respiratory chain with rotenone (110 ± 7%, n = 7) or the mitochondrial permeability transition pore with cyclosporine (111 ± 10%, n = 6). EGF increased ERK1/2 phosphorylation (136 ± 8% of control, n = 9, P < 0.05), which was blunted by 5-HD (97 ± 5%, n = 4), suggesting that ERK1/2 activation is downstream of mitochondrial oxidative stress. Finally, stretch increased Ser703 Na+/H+ exchanger-1 (NHE-1) phosphorylation by 172 ± 24% of control (n = 4, P < 0.05), an effect that was cancelled by AG1478 (94 ± 17%, n = 4). In conclusion, our data show for the first time that EGFR transactivation is crucial in the chain of events leading to the Anrep effect. Facultad de Ciencias Médicas |
description |
Myocardial stretch elicits a biphasic contractile response: the Frank-Starling mechanism followed by the slow force response (SFR) or Anrep effect. In this study we hypothesized that the SFR depends on epidermal growth factor receptor (EGFR) transactivation after the myocardial stretch-induced angiotensin II (Ang II)/endothelin (ET) release. Experiments were performed in isolated cat papillary muscles stretched from 92 to 98% of the length at which maximal twitch force was developed (Lmax). The SFR was 123 ± 1% of the immediate rapid phase (n = 6, P < 0.05) and was blunted by preventing EGFR transactivation with the Src-kinase inhibitor PP1 (99 ± 2%, n = 4), matrix metalloproteinase inhibitor MMPI (108 ± 4%, n = 11), the EGFR blocker AG1478 (98 ± 2%, n = 6) or the mitochondrial transition pore blocker clyclosporine (99 ± 3%, n = 6). Stretch increased ERK1/2 phosphorylation by 196 ± 17% of control (n = 7, P < 0.05), an effect that was prevented by PP1 (124 ± 22%, n = 7) and AG1478 (131 ± 17%, n = 4). In myocardial slices, Ang II (which enhances ET mRNA) or endothelin-1 (ET-1)-induced increase in O2- production (146 ± 14%, n = 9, and 191 ± 17%, n = 13, of control, respectively, P < 0.05) was cancelled by AG1478 (94 ± 5%, n = 12, and 98 ± 15%, n = 8, respectively) or PP1 (100 ± 4%, n = 6, and 99 ± 8%, n = 3, respectively). EGF increased O2- production by 149 ± 4% of control (n = 9, P < 0.05), an effect cancelled by inhibiting NADPH oxidase with apocynin (110 ± 6% n = 7), mKATP channels with 5-hydroxydecanoic acid (5-HD; 105 ± 5%, n = 8), the respiratory chain with rotenone (110 ± 7%, n = 7) or the mitochondrial permeability transition pore with cyclosporine (111 ± 10%, n = 6). EGF increased ERK1/2 phosphorylation (136 ± 8% of control, n = 9, P < 0.05), which was blunted by 5-HD (97 ± 5%, n = 4), suggesting that ERK1/2 activation is downstream of mitochondrial oxidative stress. Finally, stretch increased Ser703 Na+/H+ exchanger-1 (NHE-1) phosphorylation by 172 ± 24% of control (n = 4, P < 0.05), an effect that was cancelled by AG1478 (94 ± 17%, n = 4). In conclusion, our data show for the first time that EGFR transactivation is crucial in the chain of events leading to the Anrep effect. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
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http://sedici.unlp.edu.ar/handle/10915/82420 |
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http://sedici.unlp.edu.ar/handle/10915/82420 |
dc.language.none.fl_str_mv |
eng |
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eng |
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info:eu-repo/semantics/altIdentifier/issn/0022-3751 info:eu-repo/semantics/altIdentifier/doi/10.1113/jphysiol.2009.186619 |
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info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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openAccess |
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http://creativecommons.org/licenses/by-nc-sa/4.0/ Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) |
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SEDICI (UNLP) - Universidad Nacional de La Plata |
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