Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways

Autores
Aiello, Ernesto Alejandro; Villa-Abrille, María Celeste; Dulce, Raul; Cingolani, Horacio Eugenio; Perez, Nestor Gustavo
Año de publicación
2005
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
This study aimed to explore the signaling pathways involved in the positive inotropic effect (PIE) of low doses of endothelin-1 (ET-1). Cat papillary muscles were used for force and intracellular Na(+) concentration (Na(+)(i)) measurements, and isolated cat ventricular myocytes for patch-clamp experiments. ET-1 (5 nmol/L) induced a PIE and an associated increase in Na(+)(i) that were abolished by Na(+)/H(+) exchanger (NHE) inhibition with HOE642. Reverse-mode Na(+)/Ca(2+) exchanger (NCX) blockade with KB-R7943 reversed the ET-1-induced PIE. These results suggest that the ET-1-induced PIE is totally attributable to the NHE-mediated Na(+)(i) increase. However, an additional direct stimulating effect of ET-1 on NCX after the necessary increase in Na(+)(i) could occur. Thus, the ET-1-induced increase in Na(+)(i) and contractility was compared with that induced by partial inhibition of the Na(+)/K(+) ATPase by lowering extracellular K(+) (K(+)(o)). For a given Na(+)(i), ET-1 induced a greater PIE than low K(+)(o). In the presence of HOE642 and after increasing contractility and Na(+)(i) by low K(+)(o), ET-1 induced an additional PIE that was reversed by KB-R7943 or the protein kinase C (PKC) inhibitor chelerythrine. ET-1 increased the NCX current and negatively shifted the NCX reversal potential (E(NCX)). HOE642 attenuated the increase in NCX outward current and abolished the E(NCX) shift. These results indicate that whereas the NHE-mediated ET-1-induced increase in Na(+)(i) seems to be mandatory to drive NCX in reverse and enhance contractility, Na(+)(i)-independent and PKC-dependent NCX stimulation appears to additionally contribute to the PIE. However, it is important to stress that the latter can only occur after the primary participation of the former.
Fil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Villa-Abrille, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Dulce, Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Materia
Endothelins
Na+/Ca2+ Exchanger
Myocardial Contractility
Intracellular Fluids
Sodium-Calcium
Papillary Muscles
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/36275
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/36275
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathwaysAiello, Ernesto AlejandroVilla-Abrille, María CelesteDulce, RaulCingolani, Horacio EugenioPerez, Nestor GustavoEndothelinsNa+/Ca2+ ExchangerMyocardial ContractilityIntracellular FluidsSodium-CalciumPapillary Muscleshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3https://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3This study aimed to explore the signaling pathways involved in the positive inotropic effect (PIE) of low doses of endothelin-1 (ET-1). Cat papillary muscles were used for force and intracellular Na(+) concentration (Na(+)(i)) measurements, and isolated cat ventricular myocytes for patch-clamp experiments. ET-1 (5 nmol/L) induced a PIE and an associated increase in Na(+)(i) that were abolished by Na(+)/H(+) exchanger (NHE) inhibition with HOE642. Reverse-mode Na(+)/Ca(2+) exchanger (NCX) blockade with KB-R7943 reversed the ET-1-induced PIE. These results suggest that the ET-1-induced PIE is totally attributable to the NHE-mediated Na(+)(i) increase. However, an additional direct stimulating effect of ET-1 on NCX after the necessary increase in Na(+)(i) could occur. Thus, the ET-1-induced increase in Na(+)(i) and contractility was compared with that induced by partial inhibition of the Na(+)/K(+) ATPase by lowering extracellular K(+) (K(+)(o)). For a given Na(+)(i), ET-1 induced a greater PIE than low K(+)(o). In the presence of HOE642 and after increasing contractility and Na(+)(i) by low K(+)(o), ET-1 induced an additional PIE that was reversed by KB-R7943 or the protein kinase C (PKC) inhibitor chelerythrine. ET-1 increased the NCX current and negatively shifted the NCX reversal potential (E(NCX)). HOE642 attenuated the increase in NCX outward current and abolished the E(NCX) shift. These results indicate that whereas the NHE-mediated ET-1-induced increase in Na(+)(i) seems to be mandatory to drive NCX in reverse and enhance contractility, Na(+)(i)-independent and PKC-dependent NCX stimulation appears to additionally contribute to the PIE. However, it is important to stress that the latter can only occur after the primary participation of the former.Fil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Villa-Abrille, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Dulce, Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaFil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; ArgentinaLippincott Williams2005-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/36275Aiello, Ernesto Alejandro; Villa-Abrille, María Celeste; Dulce, Raul; Cingolani, Horacio Eugenio; Perez, Nestor Gustavo; Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways; Lippincott Williams; Hypertension; 45; 2; 2-2005; 288-2930194-911X1524-4563CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://hyper.ahajournals.org/content/45/2/288.longinfo:eu-repo/semantics/altIdentifier/doi/10.1161/01.HYP.0000152700.58940.b2info:eu-repo/semantics/altIdentifier/pmid/15611361info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:57:32Zoai:ri.conicet.gov.ar:11336/36275instacron: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 09:57:32.509CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways
title Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways
spellingShingle Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways
Aiello, Ernesto Alejandro
Endothelins
Na+/Ca2+ Exchanger
Myocardial Contractility
Intracellular Fluids
Sodium-Calcium
Papillary Muscles
title_short Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways
title_full Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways
title_fullStr Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways
title_full_unstemmed Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways
title_sort Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways
dc.creator.none.fl_str_mv Aiello, Ernesto Alejandro
Villa-Abrille, María Celeste
Dulce, Raul
Cingolani, Horacio Eugenio
Perez, Nestor Gustavo
author Aiello, Ernesto Alejandro
author_facet Aiello, Ernesto Alejandro
Villa-Abrille, María Celeste
Dulce, Raul
Cingolani, Horacio Eugenio
Perez, Nestor Gustavo
author_role author
author2 Villa-Abrille, María Celeste
Dulce, Raul
Cingolani, Horacio Eugenio
Perez, Nestor Gustavo
author2_role author
author
author
author
dc.subject.none.fl_str_mv Endothelins
Na+/Ca2+ Exchanger
Myocardial Contractility
Intracellular Fluids
Sodium-Calcium
Papillary Muscles
topic Endothelins
Na+/Ca2+ Exchanger
Myocardial Contractility
Intracellular Fluids
Sodium-Calcium
Papillary Muscles
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv This study aimed to explore the signaling pathways involved in the positive inotropic effect (PIE) of low doses of endothelin-1 (ET-1). Cat papillary muscles were used for force and intracellular Na(+) concentration (Na(+)(i)) measurements, and isolated cat ventricular myocytes for patch-clamp experiments. ET-1 (5 nmol/L) induced a PIE and an associated increase in Na(+)(i) that were abolished by Na(+)/H(+) exchanger (NHE) inhibition with HOE642. Reverse-mode Na(+)/Ca(2+) exchanger (NCX) blockade with KB-R7943 reversed the ET-1-induced PIE. These results suggest that the ET-1-induced PIE is totally attributable to the NHE-mediated Na(+)(i) increase. However, an additional direct stimulating effect of ET-1 on NCX after the necessary increase in Na(+)(i) could occur. Thus, the ET-1-induced increase in Na(+)(i) and contractility was compared with that induced by partial inhibition of the Na(+)/K(+) ATPase by lowering extracellular K(+) (K(+)(o)). For a given Na(+)(i), ET-1 induced a greater PIE than low K(+)(o). In the presence of HOE642 and after increasing contractility and Na(+)(i) by low K(+)(o), ET-1 induced an additional PIE that was reversed by KB-R7943 or the protein kinase C (PKC) inhibitor chelerythrine. ET-1 increased the NCX current and negatively shifted the NCX reversal potential (E(NCX)). HOE642 attenuated the increase in NCX outward current and abolished the E(NCX) shift. These results indicate that whereas the NHE-mediated ET-1-induced increase in Na(+)(i) seems to be mandatory to drive NCX in reverse and enhance contractility, Na(+)(i)-independent and PKC-dependent NCX stimulation appears to additionally contribute to the PIE. However, it is important to stress that the latter can only occur after the primary participation of the former.
Fil: Aiello, Ernesto Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Villa-Abrille, María Celeste. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Dulce, Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Cingolani, Horacio Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
Fil: Perez, Nestor Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Investigaciones Cardiovasculares ; Argentina
description This study aimed to explore the signaling pathways involved in the positive inotropic effect (PIE) of low doses of endothelin-1 (ET-1). Cat papillary muscles were used for force and intracellular Na(+) concentration (Na(+)(i)) measurements, and isolated cat ventricular myocytes for patch-clamp experiments. ET-1 (5 nmol/L) induced a PIE and an associated increase in Na(+)(i) that were abolished by Na(+)/H(+) exchanger (NHE) inhibition with HOE642. Reverse-mode Na(+)/Ca(2+) exchanger (NCX) blockade with KB-R7943 reversed the ET-1-induced PIE. These results suggest that the ET-1-induced PIE is totally attributable to the NHE-mediated Na(+)(i) increase. However, an additional direct stimulating effect of ET-1 on NCX after the necessary increase in Na(+)(i) could occur. Thus, the ET-1-induced increase in Na(+)(i) and contractility was compared with that induced by partial inhibition of the Na(+)/K(+) ATPase by lowering extracellular K(+) (K(+)(o)). For a given Na(+)(i), ET-1 induced a greater PIE than low K(+)(o). In the presence of HOE642 and after increasing contractility and Na(+)(i) by low K(+)(o), ET-1 induced an additional PIE that was reversed by KB-R7943 or the protein kinase C (PKC) inhibitor chelerythrine. ET-1 increased the NCX current and negatively shifted the NCX reversal potential (E(NCX)). HOE642 attenuated the increase in NCX outward current and abolished the E(NCX) shift. These results indicate that whereas the NHE-mediated ET-1-induced increase in Na(+)(i) seems to be mandatory to drive NCX in reverse and enhance contractility, Na(+)(i)-independent and PKC-dependent NCX stimulation appears to additionally contribute to the PIE. However, it is important to stress that the latter can only occur after the primary participation of the former.
publishDate 2005
dc.date.none.fl_str_mv 2005-02
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/11336/36275
Aiello, Ernesto Alejandro; Villa-Abrille, María Celeste; Dulce, Raul; Cingolani, Horacio Eugenio; Perez, Nestor Gustavo; Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways; Lippincott Williams; Hypertension; 45; 2; 2-2005; 288-293
0194-911X
1524-4563
CONICET Digital
CONICET
url http://hdl.handle.net/11336/36275
identifier_str_mv Aiello, Ernesto Alejandro; Villa-Abrille, María Celeste; Dulce, Raul; Cingolani, Horacio Eugenio; Perez, Nestor Gustavo; Endothelin-1 stimulates the Na+/Ca2+ exchanger reverse mode through intracellular Na+ (Na+i)-dependent and Na+i-independent pathways; Lippincott Williams; Hypertension; 45; 2; 2-2005; 288-293
0194-911X
1524-4563
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://hyper.ahajournals.org/content/45/2/288.long
info:eu-repo/semantics/altIdentifier/doi/10.1161/01.HYP.0000152700.58940.b2
info:eu-repo/semantics/altIdentifier/pmid/15611361
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
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str 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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score 13.070432

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