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, Raúl Ariel; De Giusti, Verónica Celeste; Aiello, Ernesto Alejandro; Hare, J. M.; Vila Petroff, Martín Gerardo
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 mMof theNOsynthase inhibitor L-NAME, cell swelling occurred in the absence of NOrelease. 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-inducedNOrelease. The swelling-induced negative inotropic effectwas 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.
Centro de Investigaciones Cardiovasculares
Materia
Ciencias Médicas
Contractile dysfunction
Hypotonic swelling
Ischaemia reperfusion
Nitric oxide
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/85202

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network_name_str SEDICI (UNLP)
spelling Hypotonic swelling promotes nitric oxide release in cardiac ventricular myocytes: Impact on swelling-induced negative inotropic effectGonano, Luis AlbertoMorell, MalenaBurgos, Juan IgnacioDulce, Raúl ArielDe Giusti, Verónica CelesteAiello, Ernesto AlejandroHare, J. M.Vila Petroff, Martín GerardoCiencias MédicasContractile dysfunctionHypotonic swellingIschaemia reperfusionNitric oxideAims 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 mMof theNOsynthase inhibitor L-NAME, cell swelling occurred in the absence of NOrelease. 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-inducedNOrelease. The swelling-induced negative inotropic effectwas 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.Centro de Investigaciones Cardiovasculares2014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf456-466http://sedici.unlp.edu.ar/handle/10915/85202enginfo:eu-repo/semantics/altIdentifier/issn/0008-6363info:eu-repo/semantics/altIdentifier/doi/10.1093/cvr/cvu230info: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:UNLP2025-09-29T11:16:25Zoai:sedici.unlp.edu.ar:10915/85202Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:16:26.094SEDICI (UNLP) - Universidad Nacional de La Platafalse
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
Ciencias Médicas
Contractile dysfunction
Hypotonic swelling
Ischaemia reperfusion
Nitric oxide
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, Raúl Ariel
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
Hare, J. M.
Vila Petroff, Martín Gerardo
author Gonano, Luis Alberto
author_facet Gonano, Luis Alberto
Morell, Malena
Burgos, Juan Ignacio
Dulce, Raúl Ariel
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
Hare, J. M.
Vila Petroff, Martín Gerardo
author_role author
author2 Morell, Malena
Burgos, Juan Ignacio
Dulce, Raúl Ariel
De Giusti, Verónica Celeste
Aiello, Ernesto Alejandro
Hare, J. M.
Vila Petroff, Martín Gerardo
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Contractile dysfunction
Hypotonic swelling
Ischaemia reperfusion
Nitric oxide
topic Ciencias Médicas
Contractile dysfunction
Hypotonic swelling
Ischaemia reperfusion
Nitric oxide
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 mMof theNOsynthase inhibitor L-NAME, cell swelling occurred in the absence of NOrelease. 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-inducedNOrelease. The swelling-induced negative inotropic effectwas 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.
Centro de Investigaciones Cardiovasculares
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 mMof theNOsynthase inhibitor L-NAME, cell swelling occurred in the absence of NOrelease. 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-inducedNOrelease. The swelling-induced negative inotropic effectwas 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
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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status_str publishedVersion
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info:eu-repo/semantics/altIdentifier/doi/10.1093/cvr/cvu230
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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)
eu_rights_str_mv openAccess
rights_invalid_str_mv 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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instname:Universidad Nacional de La Plata
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instname_str Universidad Nacional de La Plata
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
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