Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats

Autores
Capelari, Diego Nicolás; Sánchez, Susana I.; Ortega, Hugo H.; Ciuffo, Gladys Maria; Fuentes, Lucia Beatriz
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The renin-angiotensin system (RAS) has been implicated in pulmonary hypertension and pulmonary fibrosis. In the present study, we examined the effects of maternal exposure to captopril (2.85. mg/kg/day) during late pregnancy (G13-G21) on postnatal rat lung development. Treatment with captopril during late pregnancy caused a significant decrease in ACE activity in P0 rats. Body weight decreased at P0 (p < 0.001), P8 and P15 (p < 0.01) in captopril-treated rats. Lung weight of P0 and P8 pups was lower in treated-animals (p.< 0.05). Lungs from captopril-treated animals showed impaired alveolar formation, with enlarged distal airway spaces at P8, P15 and P30. Interalveolar wall distance measured by mean linear intercept increased in treated vs. age-matched animals at P8, P15 (p < 0.001) and P30 (p < 0.05) resembling new bronchopulmonary dysplasia. In control animals, the proliferating cell nuclear antigen (PCNA) marker was higher at P0 and then drops gradually, while in captopril-treated animals PCNA marker remains higher at all stages studied. α-Smooth muscle actin (α-SMA), a marker of fibroblast differentiation into myofibroblasts, was higher at the tips of developing secondary septa in captopril-treated lungs at P8 and P15. The increased expression of PCNA and α-SMA in treated pups suggest that beyond the effect caused by captopril, the developing lungs have the capacity to recover once the treatment was stopped. Taking together the low weight, histomorphological changes and increased expression of cellular markers caused by ACE inhibition during late pregnancy, it appears that the RAS could be an intrinsic factor involved in secondary septa formation during lung development.
Fil: Capelari, Diego Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Sánchez, Susana I.. Universidad Nacional de San Luis; Argentina
Fil: Ortega, Hugo H.. Universidad Nacional del Litoral; Argentina
Fil: Ciuffo, Gladys Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Fuentes, Lucia Beatriz. Universidad Nacional de San Luis; Argentina
Materia
ANGIOTENSIN-CONVERTING ENZYME
CAPTOPRIL
CELLULAR PROLIFERATION
POSTNATAL LUNG DEVELOPMENT
PULMONARY DYSPLASIA
RENIN ANGIOTENSIN SYSTEM
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:11336/148321
Acceder
id CONICETDig_d6f47204c696fedff258220866ba74ad
oai_identifier_str oai:ri.conicet.gov.ar:11336/148321
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Effects of maternal captopril treatment during late pregnancy on neonatal lung development in ratsCapelari, Diego NicolásSánchez, Susana I.Ortega, Hugo H.Ciuffo, Gladys MariaFuentes, Lucia BeatrizANGIOTENSIN-CONVERTING ENZYMECAPTOPRILCELLULAR PROLIFERATIONPOSTNATAL LUNG DEVELOPMENTPULMONARY DYSPLASIARENIN ANGIOTENSIN SYSTEMhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The renin-angiotensin system (RAS) has been implicated in pulmonary hypertension and pulmonary fibrosis. In the present study, we examined the effects of maternal exposure to captopril (2.85. mg/kg/day) during late pregnancy (G13-G21) on postnatal rat lung development. Treatment with captopril during late pregnancy caused a significant decrease in ACE activity in P0 rats. Body weight decreased at P0 (p < 0.001), P8 and P15 (p < 0.01) in captopril-treated rats. Lung weight of P0 and P8 pups was lower in treated-animals (p.< 0.05). Lungs from captopril-treated animals showed impaired alveolar formation, with enlarged distal airway spaces at P8, P15 and P30. Interalveolar wall distance measured by mean linear intercept increased in treated vs. age-matched animals at P8, P15 (p < 0.001) and P30 (p < 0.05) resembling new bronchopulmonary dysplasia. In control animals, the proliferating cell nuclear antigen (PCNA) marker was higher at P0 and then drops gradually, while in captopril-treated animals PCNA marker remains higher at all stages studied. α-Smooth muscle actin (α-SMA), a marker of fibroblast differentiation into myofibroblasts, was higher at the tips of developing secondary septa in captopril-treated lungs at P8 and P15. The increased expression of PCNA and α-SMA in treated pups suggest that beyond the effect caused by captopril, the developing lungs have the capacity to recover once the treatment was stopped. Taking together the low weight, histomorphological changes and increased expression of cellular markers caused by ACE inhibition during late pregnancy, it appears that the RAS could be an intrinsic factor involved in secondary septa formation during lung development.Fil: Capelari, Diego Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Sánchez, Susana I.. Universidad Nacional de San Luis; ArgentinaFil: Ortega, Hugo H.. Universidad Nacional del Litoral; ArgentinaFil: Ciuffo, Gladys Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Fuentes, Lucia Beatriz. Universidad Nacional de San Luis; ArgentinaElsevier Science2012-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/148321Capelari, Diego Nicolás; Sánchez, Susana I.; Ortega, Hugo H.; Ciuffo, Gladys Maria; Fuentes, Lucia Beatriz; Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats; Elsevier Science; Regulatory Peptides; 177; 1-3; 8-2012; 97-1060167-0115CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0167011512001590info:eu-repo/semantics/altIdentifier/doi/10.1016/j.regpep.2012.05.092info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:24Zoai:ri.conicet.gov.ar:11336/148321instacron: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 09:43:24.697CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats
title Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats
spellingShingle Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats
Capelari, Diego Nicolás
ANGIOTENSIN-CONVERTING ENZYME
CAPTOPRIL
CELLULAR PROLIFERATION
POSTNATAL LUNG DEVELOPMENT
PULMONARY DYSPLASIA
RENIN ANGIOTENSIN SYSTEM
title_short Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats
title_full Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats
title_fullStr Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats
title_full_unstemmed Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats
title_sort Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats
dc.creator.none.fl_str_mv Capelari, Diego Nicolás
Sánchez, Susana I.
Ortega, Hugo H.
Ciuffo, Gladys Maria
Fuentes, Lucia Beatriz
author Capelari, Diego Nicolás
author_facet Capelari, Diego Nicolás
Sánchez, Susana I.
Ortega, Hugo H.
Ciuffo, Gladys Maria
Fuentes, Lucia Beatriz
author_role author
author2 Sánchez, Susana I.
Ortega, Hugo H.
Ciuffo, Gladys Maria
Fuentes, Lucia Beatriz
author2_role author
author
author
author
dc.subject.none.fl_str_mv ANGIOTENSIN-CONVERTING ENZYME
CAPTOPRIL
CELLULAR PROLIFERATION
POSTNATAL LUNG DEVELOPMENT
PULMONARY DYSPLASIA
RENIN ANGIOTENSIN SYSTEM
topic ANGIOTENSIN-CONVERTING ENZYME
CAPTOPRIL
CELLULAR PROLIFERATION
POSTNATAL LUNG DEVELOPMENT
PULMONARY DYSPLASIA
RENIN ANGIOTENSIN SYSTEM
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The renin-angiotensin system (RAS) has been implicated in pulmonary hypertension and pulmonary fibrosis. In the present study, we examined the effects of maternal exposure to captopril (2.85. mg/kg/day) during late pregnancy (G13-G21) on postnatal rat lung development. Treatment with captopril during late pregnancy caused a significant decrease in ACE activity in P0 rats. Body weight decreased at P0 (p < 0.001), P8 and P15 (p < 0.01) in captopril-treated rats. Lung weight of P0 and P8 pups was lower in treated-animals (p.< 0.05). Lungs from captopril-treated animals showed impaired alveolar formation, with enlarged distal airway spaces at P8, P15 and P30. Interalveolar wall distance measured by mean linear intercept increased in treated vs. age-matched animals at P8, P15 (p < 0.001) and P30 (p < 0.05) resembling new bronchopulmonary dysplasia. In control animals, the proliferating cell nuclear antigen (PCNA) marker was higher at P0 and then drops gradually, while in captopril-treated animals PCNA marker remains higher at all stages studied. α-Smooth muscle actin (α-SMA), a marker of fibroblast differentiation into myofibroblasts, was higher at the tips of developing secondary septa in captopril-treated lungs at P8 and P15. The increased expression of PCNA and α-SMA in treated pups suggest that beyond the effect caused by captopril, the developing lungs have the capacity to recover once the treatment was stopped. Taking together the low weight, histomorphological changes and increased expression of cellular markers caused by ACE inhibition during late pregnancy, it appears that the RAS could be an intrinsic factor involved in secondary septa formation during lung development.
Fil: Capelari, Diego Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Sánchez, Susana I.. Universidad Nacional de San Luis; Argentina
Fil: Ortega, Hugo H.. Universidad Nacional del Litoral; Argentina
Fil: Ciuffo, Gladys Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Fuentes, Lucia Beatriz. Universidad Nacional de San Luis; Argentina
description The renin-angiotensin system (RAS) has been implicated in pulmonary hypertension and pulmonary fibrosis. In the present study, we examined the effects of maternal exposure to captopril (2.85. mg/kg/day) during late pregnancy (G13-G21) on postnatal rat lung development. Treatment with captopril during late pregnancy caused a significant decrease in ACE activity in P0 rats. Body weight decreased at P0 (p < 0.001), P8 and P15 (p < 0.01) in captopril-treated rats. Lung weight of P0 and P8 pups was lower in treated-animals (p.< 0.05). Lungs from captopril-treated animals showed impaired alveolar formation, with enlarged distal airway spaces at P8, P15 and P30. Interalveolar wall distance measured by mean linear intercept increased in treated vs. age-matched animals at P8, P15 (p < 0.001) and P30 (p < 0.05) resembling new bronchopulmonary dysplasia. In control animals, the proliferating cell nuclear antigen (PCNA) marker was higher at P0 and then drops gradually, while in captopril-treated animals PCNA marker remains higher at all stages studied. α-Smooth muscle actin (α-SMA), a marker of fibroblast differentiation into myofibroblasts, was higher at the tips of developing secondary septa in captopril-treated lungs at P8 and P15. The increased expression of PCNA and α-SMA in treated pups suggest that beyond the effect caused by captopril, the developing lungs have the capacity to recover once the treatment was stopped. Taking together the low weight, histomorphological changes and increased expression of cellular markers caused by ACE inhibition during late pregnancy, it appears that the RAS could be an intrinsic factor involved in secondary septa formation during lung development.
publishDate 2012
dc.date.none.fl_str_mv 2012-08
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/11336/148321
Capelari, Diego Nicolás; Sánchez, Susana I.; Ortega, Hugo H.; Ciuffo, Gladys Maria; Fuentes, Lucia Beatriz; Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats; Elsevier Science; Regulatory Peptides; 177; 1-3; 8-2012; 97-106
0167-0115
CONICET Digital
CONICET
url http://hdl.handle.net/11336/148321
identifier_str_mv Capelari, Diego Nicolás; Sánchez, Susana I.; Ortega, Hugo H.; Ciuffo, Gladys Maria; Fuentes, Lucia Beatriz; Effects of maternal captopril treatment during late pregnancy on neonatal lung development in rats; Elsevier Science; Regulatory Peptides; 177; 1-3; 8-2012; 97-106
0167-0115
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0167011512001590
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.regpep.2012.05.092
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
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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 13.13397

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