Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect
- Autores
- Gonano, Luis Alberto; Morell, Malena; Burgos, Juan Ignacio; Dulce, Raul; de Giusti, Verónica Celeste; Aiello, Ernesto Alejandro; Hare, Joshua Michael; Vila Petroff, Martin Gerarde
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Aims: Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias. We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. Methods and results: Superfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient, and increased NO-sensitive 4-amino-5-methylamino-2′ ,7′ -difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mM of the NO synthase inhibitor L-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either L-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca2+ release. Conclusions: Our findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling.
Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Morell, Malena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Burgos, Juan Ignacio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Dulce, Raul. University Of Miami; Estados Unidos
Fil: de Giusti, Verónica Celeste. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Hare, Joshua Michael. University Of Miami; Estados Unidos
Fil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina - Materia
-
Hypotonic Swelling
Nitric Oxide
Contractile Dysfunction
Ischemia Reperfusion - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/12019
Ver los metadatos del registro completo
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Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effectGonano, Luis AlbertoMorell, MalenaBurgos, Juan IgnacioDulce, Raulde Giusti, Verónica CelesteAiello, Ernesto AlejandroHare, Joshua MichaelVila Petroff, Martin GerardeHypotonic SwellingNitric OxideContractile DysfunctionIschemia Reperfusionhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Aims: Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias. We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. Methods and results: Superfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient, and increased NO-sensitive 4-amino-5-methylamino-2′ ,7′ -difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mM of the NO synthase inhibitor L-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either L-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca2+ release. Conclusions: Our findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling.Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Morell, Malena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Burgos, Juan Ignacio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Dulce, Raul. University Of Miami; Estados UnidosFil: de Giusti, Verónica Celeste. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Hare, Joshua Michael. University Of Miami; Estados UnidosFil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaOxford University Press2014-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/12019Gonano, Luis Alberto; Morell, Malena; Burgos, Juan Ignacio; Dulce, Raul; de Giusti, Verónica Celeste; et al.; Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect; Oxford University Press; Cardiovascular Research; 104; 3; 10-2014; 456-4660008-6363enginfo:eu-repo/semantics/altIdentifier/doi/10.1093/cvr/cvu230info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvu230info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296110/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:04:18Zoai:ri.conicet.gov.ar:11336/12019instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:04:18.613CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect |
title |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect |
spellingShingle |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect Gonano, Luis Alberto Hypotonic Swelling Nitric Oxide Contractile Dysfunction Ischemia Reperfusion |
title_short |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect |
title_full |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect |
title_fullStr |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect |
title_full_unstemmed |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect |
title_sort |
Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect |
dc.creator.none.fl_str_mv |
Gonano, Luis Alberto Morell, Malena Burgos, Juan Ignacio Dulce, Raul de Giusti, Verónica Celeste Aiello, Ernesto Alejandro Hare, Joshua Michael Vila Petroff, Martin Gerarde |
author |
Gonano, Luis Alberto |
author_facet |
Gonano, Luis Alberto Morell, Malena Burgos, Juan Ignacio Dulce, Raul de Giusti, Verónica Celeste Aiello, Ernesto Alejandro Hare, Joshua Michael Vila Petroff, Martin Gerarde |
author_role |
author |
author2 |
Morell, Malena Burgos, Juan Ignacio Dulce, Raul de Giusti, Verónica Celeste Aiello, Ernesto Alejandro Hare, Joshua Michael Vila Petroff, Martin Gerarde |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
Hypotonic Swelling Nitric Oxide Contractile Dysfunction Ischemia Reperfusion |
topic |
Hypotonic Swelling Nitric Oxide Contractile Dysfunction Ischemia Reperfusion |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
Aims: Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias. We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. Methods and results: Superfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient, and increased NO-sensitive 4-amino-5-methylamino-2′ ,7′ -difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mM of the NO synthase inhibitor L-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either L-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca2+ release. Conclusions: Our findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling. Fil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina Fil: Morell, Malena. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina Fil: Burgos, Juan Ignacio. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina Fil: Dulce, Raul. University Of Miami; Estados Unidos Fil: de Giusti, Verónica Celeste. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina Fil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina Fil: Hare, Joshua Michael. University Of Miami; Estados Unidos Fil: Vila Petroff, Martin Gerarde. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina |
description |
Aims: Cardiomyocyte swelling occurs in multiple pathological situations and has been associated with contractile dysfunction, cell death, and enhanced propensity to arrhythmias. We investigate whether hypotonic swelling promotes nitric oxide (NO) release in cardiomyocytes, and whether it impacts on swelling-induced contractile dysfunction. Methods and results: Superfusing rat cardiomyocytes with a hypotonic solution (HS; 217 mOsm), increased cell volume, reduced myocyte contraction and Ca2+ transient, and increased NO-sensitive 4-amino-5-methylamino-2′ ,7′ -difluorofluorescein diacetate (DAF-FM) fluorescence. When cells were exposed to HS + 2.5 mM of the NO synthase inhibitor L-NAME, cell swelling occurred in the absence of NO release. Swelling-induced NO release was also prevented by the nitric oxide synthase 1 (NOS1) inhibitor, nitroguanidine, and significantly reduced in NOS1 knockout mice. Additionally, colchicine (inhibitor of microtubule polymerization) prevented the increase in DAF-FM fluorescence induced by HS, indicating that microtubule integrity is necessary for swelling-induced NO release. The swelling-induced negative inotropic effect was exacerbated in the presence of either L-NAME, nitroguandine, the guanylate cyclase inhibitor, ODQ, or the PKG inhibitor, KT5823, suggesting that NOS1-derived NO provides contractile support via a cGMP/PKG-dependent mechanism. Indeed, ODQ reduced Ca2+ wave velocity and both ODQ and KT5823 reduced the HS-induced increment in ryanodine receptor (RyR2, Ser2808) phosphorylation, suggesting that in this context, cGMP/PKG may contribute to preserve contractile function by enhancing sarcoplasmic reticulum Ca2+ release. Conclusions: Our findings suggest a novel mechanism for NO release in cardiomyocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hypotonic swelling. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-10 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/12019 Gonano, Luis Alberto; Morell, Malena; Burgos, Juan Ignacio; Dulce, Raul; de Giusti, Verónica Celeste; et al.; Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect; Oxford University Press; Cardiovascular Research; 104; 3; 10-2014; 456-466 0008-6363 |
url |
http://hdl.handle.net/11336/12019 |
identifier_str_mv |
Gonano, Luis Alberto; Morell, Malena; Burgos, Juan Ignacio; Dulce, Raul; de Giusti, Verónica Celeste; et al.; Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: impact on swelling-induced negative inotropic effect; Oxford University Press; Cardiovascular Research; 104; 3; 10-2014; 456-466 0008-6363 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1093/cvr/cvu230 info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvu230 info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4296110/ |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Oxford University Press |
publisher.none.fl_str_mv |
Oxford University Press |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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