Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | https://doi.org/10.3389/fnins.2021.624249 http://hdl.handle.net/1843/56302 https://orcid.org/0000-0003-3678-118X https://orcid.org/0000-0002-6174-8157 https://orcid.org/0000-0003-2823-4530 https://orcid.org/0000-0001-9483-4206 |
Resumo: | Previous data showed hypertensive rats subjected to chronic intracerebroventricular (ICV) infusion of angiotensin-(1-7) presented attenuation of arterial hypertension, improvement of baroreflex sensitivity, restoration of cardiac autonomic balance and a shift of cardiac renin-angiotensin system (RAS) balance toward Ang-(1-7)/Mas receptor. In the present study, we investigated putative central mechanisms related to the antihypertensive effect induced by ICV Ang-(1-7), including inflammatory mediators and the expression/activity of the RAS components in hypertensive rats. Furthermore, we performed a proteomic analysis to evaluate differentially regulated proteins in the hypothalamus of these animals. For this, Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats (TG) were subjected to 14 days of ICV infusion with Ang-(1-7) (200 ng/h) or 0.9% sterile saline (0.5 µl/h) through osmotic mini-pumps. We observed that Ang-(1-7) treatment modulated inflammatory cytokines by decreasing TNF-α levels while increasing the anti-inflammatory IL-10. Moreover, we showed a reduction in ACE activity and gene expression of AT1 receptor and iNOS. Finally, our proteomic evaluation suggested an anti-inflammatory mechanism of Ang-(1-7) toward the ROS modulators Uchl1 and Prdx1. |
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2023-07-14T20:36:54Z2023-07-14T20:36:54Z2021-04-2315https://doi.org/10.3389/fnins.2021.6242491662-453Xhttp://hdl.handle.net/1843/56302https://orcid.org/0000-0003-3678-118Xhttps://orcid.org/0000-0002-6174-8157https://orcid.org/0000-0003-2823-4530https://orcid.org/0000-0001-9483-4206Previous data showed hypertensive rats subjected to chronic intracerebroventricular (ICV) infusion of angiotensin-(1-7) presented attenuation of arterial hypertension, improvement of baroreflex sensitivity, restoration of cardiac autonomic balance and a shift of cardiac renin-angiotensin system (RAS) balance toward Ang-(1-7)/Mas receptor. In the present study, we investigated putative central mechanisms related to the antihypertensive effect induced by ICV Ang-(1-7), including inflammatory mediators and the expression/activity of the RAS components in hypertensive rats. Furthermore, we performed a proteomic analysis to evaluate differentially regulated proteins in the hypothalamus of these animals. For this, Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats (TG) were subjected to 14 days of ICV infusion with Ang-(1-7) (200 ng/h) or 0.9% sterile saline (0.5 µl/h) through osmotic mini-pumps. We observed that Ang-(1-7) treatment modulated inflammatory cytokines by decreasing TNF-α levels while increasing the anti-inflammatory IL-10. Moreover, we showed a reduction in ACE activity and gene expression of AT1 receptor and iNOS. Finally, our proteomic evaluation suggested an anti-inflammatory mechanism of Ang-(1-7) toward the ROS modulators Uchl1 and Prdx1.Dados anteriores mostraram que ratos hipertensos submetidos à infusão crônica intracerebroventricular (ICV) de angiotensina-(1-7) apresentaram atenuação da hipertensão arterial, melhora da sensibilidade do barorreflexo, restauração do equilíbrio autonômico cardíaco e alteração do equilíbrio do sistema renina-angiotensina (SRA) cardíaco para o receptor Ang-(1-7)/Mas. No presente estudo, investigamos os supostos mecanismos centrais relacionados ao efeito anti-hipertensivo induzido pelo ICV Ang-(1-7), incluindo mediadores inflamatórios e a expressão/atividade dos componentes do SRA em ratos hipertensos. Além disso, realizamos uma análise proteômica para avaliar proteínas diferencialmente reguladas no hipotálamo desses animais. Para isso, ratos Sprague Dawley (SD) e transgênicos (mRen2)27 hipertensos (TG) foram submetidos a 14 dias de infusão ICV com Ang-(1-7) (200 ng/h) ou soro fisiológico 0,9% estéril (0,5 µl/ h) através de minibombas osmóticas. Observamos que o tratamento com Ang-(1-7) modulou as citocinas inflamatórias diminuindo os níveis de TNF-α e aumentando o anti-inflamatório IL-10. Além disso, mostramos uma redução na atividade da ECA e na expressão gênica do receptor AT1 e iNOS. Finalmente, nossa avaliação proteômica sugeriu um mecanismo anti-inflamatório de Ang-(1-7) para os moduladores de ROS Uchl1 e Prdx1.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorengUniversidade Federal de Minas GeraisUFMGBrasilICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICAICB - DEPARTAMENTO DE MORFOLOGIAICB - DEPARTAMENTO DE PARASITOLOGIAFrontiers in NeuroscienceAngiotensinasHipotálamoRatos transgênicosHipertensãoCitocinasÓxido nítrico sintase tipo IIBarorreflexoProteômicaAngiotensin-(1-7)HypothalamusHypertensive transgenic (mRen2)27 ratsCytokinesiNOSROS modulatorsAngiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 ratsMecanismos centrais de angiotensina-(1-7) após infusão ICV em ratos hipertensos transgênicos (mRen2)27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://www.frontiersin.org/articles/10.3389/fnins.2021.624249/fullLucas Miranda KangussuMarcella Nunes de Melo BragaBruna Soares de Souza Lima RodriguesRobson Augusto Souza dos SantosHélida Monteiro de AndradeMaria José Campagnole dos Santosapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/56302/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALAngiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats.pdfAngiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats.pdfapplication/pdf73178979https://repositorio.ufmg.br/bitstream/1843/56302/2/Angiotensin-%281-7%29%20central%20mechanisms%20after%20ICV%20infusion%20in%20hypertensive%20transgenic%20%28mRen2%2927%20rats.pdf74f9266c9a8ba2aaa978267f85ab148eMD521843/563022023-07-14 17:36:54.247oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-07-14T20:36:54Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats |
dc.title.alternative.pt_BR.fl_str_mv |
Mecanismos centrais de angiotensina-(1-7) após infusão ICV em ratos hipertensos transgênicos (mRen2)27 |
title |
Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats |
spellingShingle |
Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats Lucas Miranda Kangussu Angiotensin-(1-7) Hypothalamus Hypertensive transgenic (mRen2)27 rats Cytokines iNOS ROS modulators Angiotensinas Hipotálamo Ratos transgênicos Hipertensão Citocinas Óxido nítrico sintase tipo II Barorreflexo Proteômica |
title_short |
Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats |
title_full |
Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats |
title_fullStr |
Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats |
title_full_unstemmed |
Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats |
title_sort |
Angiotensin-(1-7) central mechanisms after ICV infusion in hypertensive transgenic (mRen2)27 rats |
author |
Lucas Miranda Kangussu |
author_facet |
Lucas Miranda Kangussu Marcella Nunes de Melo Braga Bruna Soares de Souza Lima Rodrigues Robson Augusto Souza dos Santos Hélida Monteiro de Andrade Maria José Campagnole dos Santos |
author_role |
author |
author2 |
Marcella Nunes de Melo Braga Bruna Soares de Souza Lima Rodrigues Robson Augusto Souza dos Santos Hélida Monteiro de Andrade Maria José Campagnole dos Santos |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Lucas Miranda Kangussu Marcella Nunes de Melo Braga Bruna Soares de Souza Lima Rodrigues Robson Augusto Souza dos Santos Hélida Monteiro de Andrade Maria José Campagnole dos Santos |
dc.subject.por.fl_str_mv |
Angiotensin-(1-7) Hypothalamus Hypertensive transgenic (mRen2)27 rats Cytokines iNOS ROS modulators |
topic |
Angiotensin-(1-7) Hypothalamus Hypertensive transgenic (mRen2)27 rats Cytokines iNOS ROS modulators Angiotensinas Hipotálamo Ratos transgênicos Hipertensão Citocinas Óxido nítrico sintase tipo II Barorreflexo Proteômica |
dc.subject.other.pt_BR.fl_str_mv |
Angiotensinas Hipotálamo Ratos transgênicos Hipertensão Citocinas Óxido nítrico sintase tipo II Barorreflexo Proteômica |
description |
Previous data showed hypertensive rats subjected to chronic intracerebroventricular (ICV) infusion of angiotensin-(1-7) presented attenuation of arterial hypertension, improvement of baroreflex sensitivity, restoration of cardiac autonomic balance and a shift of cardiac renin-angiotensin system (RAS) balance toward Ang-(1-7)/Mas receptor. In the present study, we investigated putative central mechanisms related to the antihypertensive effect induced by ICV Ang-(1-7), including inflammatory mediators and the expression/activity of the RAS components in hypertensive rats. Furthermore, we performed a proteomic analysis to evaluate differentially regulated proteins in the hypothalamus of these animals. For this, Sprague Dawley (SD) and transgenic (mRen2)27 hypertensive rats (TG) were subjected to 14 days of ICV infusion with Ang-(1-7) (200 ng/h) or 0.9% sterile saline (0.5 µl/h) through osmotic mini-pumps. We observed that Ang-(1-7) treatment modulated inflammatory cytokines by decreasing TNF-α levels while increasing the anti-inflammatory IL-10. Moreover, we showed a reduction in ACE activity and gene expression of AT1 receptor and iNOS. Finally, our proteomic evaluation suggested an anti-inflammatory mechanism of Ang-(1-7) toward the ROS modulators Uchl1 and Prdx1. |
publishDate |
2021 |
dc.date.issued.fl_str_mv |
2021-04-23 |
dc.date.accessioned.fl_str_mv |
2023-07-14T20:36:54Z |
dc.date.available.fl_str_mv |
2023-07-14T20:36:54Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/56302 |
dc.identifier.doi.pt_BR.fl_str_mv |
https://doi.org/10.3389/fnins.2021.624249 |
dc.identifier.issn.pt_BR.fl_str_mv |
1662-453X |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0003-3678-118X https://orcid.org/0000-0002-6174-8157 https://orcid.org/0000-0003-2823-4530 https://orcid.org/0000-0001-9483-4206 |
url |
https://doi.org/10.3389/fnins.2021.624249 http://hdl.handle.net/1843/56302 https://orcid.org/0000-0003-3678-118X https://orcid.org/0000-0002-6174-8157 https://orcid.org/0000-0003-2823-4530 https://orcid.org/0000-0001-9483-4206 |
identifier_str_mv |
1662-453X |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Frontiers in Neuroscience |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
ICB - DEPARTAMENTO DE FISIOLOGIA E BIOFÍSICA ICB - DEPARTAMENTO DE MORFOLOGIA ICB - DEPARTAMENTO DE PARASITOLOGIA |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
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