Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol

Autores
Diez, Emiliano Raúl; Altamirano, Berta Liliana; García, Isabel Mercedes; Mazzei, Luciana Jorgelina; Prado, Natalia Jorgelina; Fornes, Miguel Walter; Cuello Carrión, Fernando Darío; Ponce Zumino, Amira Zulma; Ferder, León; Manucha, Walter Ariel Fernando
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia–reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.
Fil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Altamirano, Liliana Berta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina
Fil: García, Isabel Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Fornes, Miguel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ponce Zumino, Amira Zulma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ferder, León. Universidad de Puerto Rico; Puerto Rico
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina
Materia
Arrhythmias
Paricalcitol
Reperfusion Injury
Ureteral Obstruction
Ventricular Remodeling
Vitamin D Receptor
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:11336/32465
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/32465
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by ParicalcitolDiez, Emiliano RaúlAltamirano, Berta LilianaGarcía, Isabel MercedesMazzei, Luciana JorgelinaPrado, Natalia JorgelinaFornes, Miguel WalterCuello Carrión, Fernando DaríoPonce Zumino, Amira ZulmaFerder, LeónManucha, Walter Ariel FernandoArrhythmiasParicalcitolReperfusion InjuryUreteral ObstructionVentricular RemodelingVitamin D Receptorhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia–reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.Fil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Altamirano, Liliana Berta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; ArgentinaFil: García, Isabel Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Fornes, Miguel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ponce Zumino, Amira Zulma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Ferder, León. Universidad de Puerto Rico; Puerto RicoFil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; ArgentinaSage Publications2014-06info: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/11336/32465Diez, Emiliano Raúl; Altamirano, Berta Liliana; García, Isabel Mercedes; Mazzei, Luciana Jorgelina; Prado, Natalia Jorgelina; et al.; Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol; Sage Publications; Journal Of Cardiovascular Pharmacology And Therapeutics; 20; 2; 6-2014; 211-2201074-2484CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journals.sagepub.com/doi/abs/10.1177/1074248414538704info:eu-repo/semantics/altIdentifier/doi/10.1177/1074248414538704info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:11:59Zoai:ri.conicet.gov.ar:11336/32465instacron: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:34982025-09-10 13:11:59.854CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
title Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
spellingShingle Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
Diez, Emiliano Raúl
Arrhythmias
Paricalcitol
Reperfusion Injury
Ureteral Obstruction
Ventricular Remodeling
Vitamin D Receptor
title_short Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
title_full Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
title_fullStr Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
title_full_unstemmed Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
title_sort Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol
dc.creator.none.fl_str_mv Diez, Emiliano Raúl
Altamirano, Berta Liliana
García, Isabel Mercedes
Mazzei, Luciana Jorgelina
Prado, Natalia Jorgelina
Fornes, Miguel Walter
Cuello Carrión, Fernando Darío
Ponce Zumino, Amira Zulma
Ferder, León
Manucha, Walter Ariel Fernando
author Diez, Emiliano Raúl
author_facet Diez, Emiliano Raúl
Altamirano, Berta Liliana
García, Isabel Mercedes
Mazzei, Luciana Jorgelina
Prado, Natalia Jorgelina
Fornes, Miguel Walter
Cuello Carrión, Fernando Darío
Ponce Zumino, Amira Zulma
Ferder, León
Manucha, Walter Ariel Fernando
author_role author
author2 Altamirano, Berta Liliana
García, Isabel Mercedes
Mazzei, Luciana Jorgelina
Prado, Natalia Jorgelina
Fornes, Miguel Walter
Cuello Carrión, Fernando Darío
Ponce Zumino, Amira Zulma
Ferder, León
Manucha, Walter Ariel Fernando
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Arrhythmias
Paricalcitol
Reperfusion Injury
Ureteral Obstruction
Ventricular Remodeling
Vitamin D Receptor
topic Arrhythmias
Paricalcitol
Reperfusion Injury
Ureteral Obstruction
Ventricular Remodeling
Vitamin D Receptor
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia–reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.
Fil: Diez, Emiliano Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Altamirano, Liliana Berta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina
Fil: García, Isabel Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Mazzei, Luciana Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Prado, Natalia Jorgelina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Fornes, Miguel Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina
Fil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ponce Zumino, Amira Zulma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina
Fil: Ferder, León. Universidad de Puerto Rico; Puerto Rico
Fil: Manucha, Walter Ariel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Departamento de Patología; Argentina
description Cardiovascular disease is often associated with chronic kidney disease and vice versa; myocardial vitamin D receptors (VDRs) are among the probable links between the 2 disorders. The vitamin D receptor activator paricalcitol protects against some renal and cardiovascular complications. However, the structural and electrophysiological effects of myocardial vitamin D receptor modification and its impact on the response to ischemia–reperfusion are currently unknown. This work attempted to determine whether obstructive nephropathy induced myocardial changes (in rats) linked to vitamin D receptor deficiency and to ventricular arrhythmias in Langendorff-perfused hearts. Unilateral ureteral-obstructed and Sham-operated rats were treated with either paricalcitol (30 ng/kg/d intraperitoneal) or vehicle for 15 days. In 5 hearts from each group, we found that obstructed rats showed a reduction in VDRs and an increase in angiotensin II type 1 receptor expression (messenger RNA and protein), suffered fibrosis (determined by Masson trichrome stain) and myofibril reduction with an increase in mitochondrial size, and had dilated crests (determined by electron microscopy). These changes were reversed by paricalcitol. In 8 additional hearts per group, we found that obstructed rats showed a higher incidence of ventricular fibrillation during reperfusion (after 10 minutes of regional ischemia) than did those treated with paricalcitol. The action potential duration was prolonged throughout the experiment in paricalcitol-treated rats. We conclude that the reduction in myocardial vitamin D receptor expression in obstructed rats might be related to myocardial remodeling associated with an increase in arrhythmogenesis and that paricalcitol protects against these changes by restoring myocardial vitamin D receptor levels and prolonging action potentials.
publishDate 2014
dc.date.none.fl_str_mv 2014-06
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
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info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/32465
Diez, Emiliano Raúl; Altamirano, Berta Liliana; García, Isabel Mercedes; Mazzei, Luciana Jorgelina; Prado, Natalia Jorgelina; et al.; Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol; Sage Publications; Journal Of Cardiovascular Pharmacology And Therapeutics; 20; 2; 6-2014; 211-220
1074-2484
CONICET Digital
CONICET
url http://hdl.handle.net/11336/32465
identifier_str_mv Diez, Emiliano Raúl; Altamirano, Berta Liliana; García, Isabel Mercedes; Mazzei, Luciana Jorgelina; Prado, Natalia Jorgelina; et al.; Heart Remodeling and Ischemia–Reperfusion Arrhythmias Linked to Myocardial Vitamin D Receptors Deficiency in Obstructive Nephropathy Are Reversed by Paricalcitol; Sage Publications; Journal Of Cardiovascular Pharmacology And Therapeutics; 20; 2; 6-2014; 211-220
1074-2484
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
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eu_rights_str_mv openAccess
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dc.publisher.none.fl_str_mv Sage Publications
publisher.none.fl_str_mv Sage Publications
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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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