Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits

Autores
González, Germán Esteban; Seropian, Ignacio Miguel; Krieger, Maria Laura; Palleiro, Jimena; Lopez Verrilli, María Alejandra; Gironacci, Mariela Mercedes; Cavallero, Carmen Susana; Wilensky, Luciana; Tomasi, Victor Hugo; Gelpi, Ricardo Jorge; Morales, Maria Celina
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
To characterize the temporal activation of the renin-angiotensin system after myocardial infarction (MI) in rabbits, we examined cardiac ANG II type 1 receptor (AT1R) expression and ANG II levels from 3 h to 35 days. The effects of losartan (12.5 mg·kg−1·day−1) on functional and histomorphometric parameters when treatment was initiated early (3 h) and late (day 15) post-MI and maintained for different periods of time [short term (4 days), midterm (20 days), and long term (35 days)] were also studied. AT1R expression increased in the MI zone at 15 and 35 days (P < 0.05). ANG II levels increased (P < 0.05) in the non-MI zone at 24 h and in the MI zone as well as in plasma at 4 days and then progressively decreased until 35 days. The survival rate was significantly lower in untreated MI and early long-term-treated animals. Diastolic pressure-volume curves in MI at 35 and 56 days shifted to the right (P < 0.05). This shift was even more pronounced in long-term-treated groups (P < 0.05). Contractility decreased (P < 0.05 vs. sham) in the untreated and long-term-treated groups and was attenuated in the midterm-treated group. The early administration of losartan reduced RAM 11-positive macrophages from 4.15 ± 0.05 to 3.05 ± 0.02 cells/high-power field (HPF; P < 0.05) and CD45 RO-positive lymphocytes from 2.23 ± 0.05 to 1.48 ± 0.01 cells/HPF (P < 0.05) in the MI zone at 4 days. Long-term treatment reduced the scar collagen (MI: 70.50 ± 2.35% and MI + losartan: 57.50 ± 2.48, P < 0.05), determined the persistency of RAM 11-positive macrophages (3.02 ± 0.13 cells/HPF) and CD45 RO-positive lymphocytes (2.77 ± 0.58 cells/HPF, P < 0.05 vs. MI), and reduced the scar thinning ratio at 35 days (P < 0.05). Consequently, the temporal expressions of cardiac AT1R and ANG II post-MI in rabbits are different from those described in other species. Long-term treatment unfavorably modified post-MI remodeling, whereas midterm treatment attenuated this harmful effect. The delay in wound healing (early reduction and late persistency of inflammatory infiltrate) and adverse remodeling observed in long-term-treated animals might explain the unfavorable effect observed in rabbits.
Fil: González, Germán Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Seropian, Ignacio Miguel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Krieger, Maria Laura. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Palleiro, Jimena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Lopez Verrilli, María Alejandra. Universidad de Buenos Aires. Prog.de Invest.fisico Química (p); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gironacci, Mariela Mercedes. Universidad de Buenos Aires. Prog.de Invest.fisico Química (p); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cavallero, Carmen Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Wilensky, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Tomasi, Victor Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morales, Maria Celina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
MYOCARDIAL INFARCTION
ANGIOTENSIN II
RABBITS
VENTRICULAR REMODELING
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:11336/102548

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network_acronym_str CONICETDig
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network_name_str CONICET Digital (CONICET)
spelling Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbitsGonzález, Germán EstebanSeropian, Ignacio MiguelKrieger, Maria LauraPalleiro, JimenaLopez Verrilli, María AlejandraGironacci, Mariela MercedesCavallero, Carmen SusanaWilensky, LucianaTomasi, Victor HugoGelpi, Ricardo JorgeMorales, Maria CelinaMYOCARDIAL INFARCTIONANGIOTENSIN IIRABBITSVENTRICULAR REMODELINGhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3To characterize the temporal activation of the renin-angiotensin system after myocardial infarction (MI) in rabbits, we examined cardiac ANG II type 1 receptor (AT1R) expression and ANG II levels from 3 h to 35 days. The effects of losartan (12.5 mg·kg−1·day−1) on functional and histomorphometric parameters when treatment was initiated early (3 h) and late (day 15) post-MI and maintained for different periods of time [short term (4 days), midterm (20 days), and long term (35 days)] were also studied. AT1R expression increased in the MI zone at 15 and 35 days (P < 0.05). ANG II levels increased (P < 0.05) in the non-MI zone at 24 h and in the MI zone as well as in plasma at 4 days and then progressively decreased until 35 days. The survival rate was significantly lower in untreated MI and early long-term-treated animals. Diastolic pressure-volume curves in MI at 35 and 56 days shifted to the right (P < 0.05). This shift was even more pronounced in long-term-treated groups (P < 0.05). Contractility decreased (P < 0.05 vs. sham) in the untreated and long-term-treated groups and was attenuated in the midterm-treated group. The early administration of losartan reduced RAM 11-positive macrophages from 4.15 ± 0.05 to 3.05 ± 0.02 cells/high-power field (HPF; P < 0.05) and CD45 RO-positive lymphocytes from 2.23 ± 0.05 to 1.48 ± 0.01 cells/HPF (P < 0.05) in the MI zone at 4 days. Long-term treatment reduced the scar collagen (MI: 70.50 ± 2.35% and MI + losartan: 57.50 ± 2.48, P < 0.05), determined the persistency of RAM 11-positive macrophages (3.02 ± 0.13 cells/HPF) and CD45 RO-positive lymphocytes (2.77 ± 0.58 cells/HPF, P < 0.05 vs. MI), and reduced the scar thinning ratio at 35 days (P < 0.05). Consequently, the temporal expressions of cardiac AT1R and ANG II post-MI in rabbits are different from those described in other species. Long-term treatment unfavorably modified post-MI remodeling, whereas midterm treatment attenuated this harmful effect. The delay in wound healing (early reduction and late persistency of inflammatory infiltrate) and adverse remodeling observed in long-term-treated animals might explain the unfavorable effect observed in rabbits.Fil: González, Germán Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Seropian, Ignacio Miguel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Krieger, Maria Laura. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Palleiro, Jimena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Lopez Verrilli, María Alejandra. Universidad de Buenos Aires. Prog.de Invest.fisico Química (p); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gironacci, Mariela Mercedes. Universidad de Buenos Aires. Prog.de Invest.fisico Química (p); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cavallero, Carmen Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; ArgentinaFil: Wilensky, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Tomasi, Victor Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; ArgentinaFil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Morales, Maria Celina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Physiological Society2009-07info: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/11336/102548González, Germán Esteban; Seropian, Ignacio Miguel; Krieger, Maria Laura; Palleiro, Jimena; Lopez Verrilli, María Alejandra; et al.; Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits; American Physiological Society; American Journal of Physiology - Heart and Circulatory Physiology; 297; 1; 7-2009; 375-3860363-6135CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1152/ajpheart.00498.2007info:eu-repo/semantics/altIdentifier/url/https://journals.physiology.org/doi/full/10.1152/ajpheart.00498.2007?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed&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 Técnicas2025-09-03T09:49:55Zoai:ri.conicet.gov.ar:11336/102548instacron: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:34982025-09-03 09:49:55.94CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
title Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
spellingShingle Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
González, Germán Esteban
MYOCARDIAL INFARCTION
ANGIOTENSIN II
RABBITS
VENTRICULAR REMODELING
title_short Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
title_full Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
title_fullStr Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
title_full_unstemmed Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
title_sort Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits
dc.creator.none.fl_str_mv González, Germán Esteban
Seropian, Ignacio Miguel
Krieger, Maria Laura
Palleiro, Jimena
Lopez Verrilli, María Alejandra
Gironacci, Mariela Mercedes
Cavallero, Carmen Susana
Wilensky, Luciana
Tomasi, Victor Hugo
Gelpi, Ricardo Jorge
Morales, Maria Celina
author González, Germán Esteban
author_facet González, Germán Esteban
Seropian, Ignacio Miguel
Krieger, Maria Laura
Palleiro, Jimena
Lopez Verrilli, María Alejandra
Gironacci, Mariela Mercedes
Cavallero, Carmen Susana
Wilensky, Luciana
Tomasi, Victor Hugo
Gelpi, Ricardo Jorge
Morales, Maria Celina
author_role author
author2 Seropian, Ignacio Miguel
Krieger, Maria Laura
Palleiro, Jimena
Lopez Verrilli, María Alejandra
Gironacci, Mariela Mercedes
Cavallero, Carmen Susana
Wilensky, Luciana
Tomasi, Victor Hugo
Gelpi, Ricardo Jorge
Morales, Maria Celina
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv MYOCARDIAL INFARCTION
ANGIOTENSIN II
RABBITS
VENTRICULAR REMODELING
topic MYOCARDIAL INFARCTION
ANGIOTENSIN II
RABBITS
VENTRICULAR REMODELING
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv To characterize the temporal activation of the renin-angiotensin system after myocardial infarction (MI) in rabbits, we examined cardiac ANG II type 1 receptor (AT1R) expression and ANG II levels from 3 h to 35 days. The effects of losartan (12.5 mg·kg−1·day−1) on functional and histomorphometric parameters when treatment was initiated early (3 h) and late (day 15) post-MI and maintained for different periods of time [short term (4 days), midterm (20 days), and long term (35 days)] were also studied. AT1R expression increased in the MI zone at 15 and 35 days (P < 0.05). ANG II levels increased (P < 0.05) in the non-MI zone at 24 h and in the MI zone as well as in plasma at 4 days and then progressively decreased until 35 days. The survival rate was significantly lower in untreated MI and early long-term-treated animals. Diastolic pressure-volume curves in MI at 35 and 56 days shifted to the right (P < 0.05). This shift was even more pronounced in long-term-treated groups (P < 0.05). Contractility decreased (P < 0.05 vs. sham) in the untreated and long-term-treated groups and was attenuated in the midterm-treated group. The early administration of losartan reduced RAM 11-positive macrophages from 4.15 ± 0.05 to 3.05 ± 0.02 cells/high-power field (HPF; P < 0.05) and CD45 RO-positive lymphocytes from 2.23 ± 0.05 to 1.48 ± 0.01 cells/HPF (P < 0.05) in the MI zone at 4 days. Long-term treatment reduced the scar collagen (MI: 70.50 ± 2.35% and MI + losartan: 57.50 ± 2.48, P < 0.05), determined the persistency of RAM 11-positive macrophages (3.02 ± 0.13 cells/HPF) and CD45 RO-positive lymphocytes (2.77 ± 0.58 cells/HPF, P < 0.05 vs. MI), and reduced the scar thinning ratio at 35 days (P < 0.05). Consequently, the temporal expressions of cardiac AT1R and ANG II post-MI in rabbits are different from those described in other species. Long-term treatment unfavorably modified post-MI remodeling, whereas midterm treatment attenuated this harmful effect. The delay in wound healing (early reduction and late persistency of inflammatory infiltrate) and adverse remodeling observed in long-term-treated animals might explain the unfavorable effect observed in rabbits.
Fil: González, Germán Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Seropian, Ignacio Miguel. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Krieger, Maria Laura. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Palleiro, Jimena. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Lopez Verrilli, María Alejandra. Universidad de Buenos Aires. Prog.de Invest.fisico Química (p); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gironacci, Mariela Mercedes. Universidad de Buenos Aires. Prog.de Invest.fisico Química (p); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cavallero, Carmen Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Ciencias Biológicas. Cátedra de Fisiopatología; Argentina
Fil: Wilensky, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Tomasi, Victor Hugo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina
Fil: Gelpi, Ricardo Jorge. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Morales, Maria Celina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiopatología Cardiovascular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description To characterize the temporal activation of the renin-angiotensin system after myocardial infarction (MI) in rabbits, we examined cardiac ANG II type 1 receptor (AT1R) expression and ANG II levels from 3 h to 35 days. The effects of losartan (12.5 mg·kg−1·day−1) on functional and histomorphometric parameters when treatment was initiated early (3 h) and late (day 15) post-MI and maintained for different periods of time [short term (4 days), midterm (20 days), and long term (35 days)] were also studied. AT1R expression increased in the MI zone at 15 and 35 days (P < 0.05). ANG II levels increased (P < 0.05) in the non-MI zone at 24 h and in the MI zone as well as in plasma at 4 days and then progressively decreased until 35 days. The survival rate was significantly lower in untreated MI and early long-term-treated animals. Diastolic pressure-volume curves in MI at 35 and 56 days shifted to the right (P < 0.05). This shift was even more pronounced in long-term-treated groups (P < 0.05). Contractility decreased (P < 0.05 vs. sham) in the untreated and long-term-treated groups and was attenuated in the midterm-treated group. The early administration of losartan reduced RAM 11-positive macrophages from 4.15 ± 0.05 to 3.05 ± 0.02 cells/high-power field (HPF; P < 0.05) and CD45 RO-positive lymphocytes from 2.23 ± 0.05 to 1.48 ± 0.01 cells/HPF (P < 0.05) in the MI zone at 4 days. Long-term treatment reduced the scar collagen (MI: 70.50 ± 2.35% and MI + losartan: 57.50 ± 2.48, P < 0.05), determined the persistency of RAM 11-positive macrophages (3.02 ± 0.13 cells/HPF) and CD45 RO-positive lymphocytes (2.77 ± 0.58 cells/HPF, P < 0.05 vs. MI), and reduced the scar thinning ratio at 35 days (P < 0.05). Consequently, the temporal expressions of cardiac AT1R and ANG II post-MI in rabbits are different from those described in other species. Long-term treatment unfavorably modified post-MI remodeling, whereas midterm treatment attenuated this harmful effect. The delay in wound healing (early reduction and late persistency of inflammatory infiltrate) and adverse remodeling observed in long-term-treated animals might explain the unfavorable effect observed in rabbits.
publishDate 2009
dc.date.none.fl_str_mv 2009-07
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/11336/102548
González, Germán Esteban; Seropian, Ignacio Miguel; Krieger, Maria Laura; Palleiro, Jimena; Lopez Verrilli, María Alejandra; et al.; Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits; American Physiological Society; American Journal of Physiology - Heart and Circulatory Physiology; 297; 1; 7-2009; 375-386
0363-6135
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102548
identifier_str_mv González, Germán Esteban; Seropian, Ignacio Miguel; Krieger, Maria Laura; Palleiro, Jimena; Lopez Verrilli, María Alejandra; et al.; Effect of early versus late AT 1 receptor blockade with losartan on postmyocardial infarction ventricular remodeling in rabbits; American Physiological Society; American Journal of Physiology - Heart and Circulatory Physiology; 297; 1; 7-2009; 375-386
0363-6135
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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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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