Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
Texto Completo: | http://repositorio.ufes.br/handle/10/8008 |
Resumo: | Iron overload in human and animal models increases oxidative stress and induces cardiomyopathy. It has been suggested that vasculature could be damaged by iron overload as well, but impacts on the vascular reactivity and the mechanisms enrolled have not been understood. In this study we aimed to identify possible changes in vascular reactivity of aorta from iron overloaded rats, investigating the underlying mechanisms. Rats were randomized and treated with iron dextran, i.p., 10mg/Kg/day or 100mg/kg/day five days a week for four weeks and compared to a saline injected group (control). Systolic blood pressure was measured weekly by tail cuff plethysmography. At the end of treatment, the blood iron parameters and iron deposition in tissues was assessed, and the vascular reactivity of the isolated aorta to phenylephrine, acetylcholine, sodium nitroprusside and angiotensin was analyzed in the context of endothelium denudation and incubation with L-NAME, tiron, catalase, apocynin, allopurinol, losartan, indomethacin or SQ 29598. Chronic iron administration increased serum iron and transferrin saturation with significant deposition in the liver. Additionally, high dose iron overload significantly increased the vasoconstrictor response in aortic rings as assessed in vitro, and endothelial denudation or L-NAME incubation have smaller impact on the vascular reactivity of the iron overloaded group, while these parameters have not changed in low dose iron overload group. Nitric oxide sensible fluorescent probe DAF-2 indicated reduced nitric oxide production in moderate iron overload when compared to controls. Iron overload-induced vascular hyperactivity was reversed by incubation with tiron, catalase, apocynin, allopurinol, losartan, indomethacin and SQ 29598. Moreover, malonyldialdehyde was elevated in plasma; and superoxide anion generation and NADPH oxidase membrane-bound subunit (p22phox) expression were increased in aorta from iron-loaded rats. Result demonstrated by the first time that chronic iron overload is associated with altered vascular reactivity with loss of endothelial modulation of the vascular tone. Moreover, the iron loading-induced endothelial dysfunction and reduced nitric oxide bioavailability may be a result of increased production of reactive oxygen species and local renin-angiotensin system and by way of cyclooxygenase activation. |
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Graceli, Jones BernardesSantos, Leonardo dosMarques, Vinícius BermondXavier, Fabiano EliasMeyrelles, Silvana dos Santos2018-08-01T22:58:49Z2018-08-012018-08-01T22:58:49Z2015-06-11Iron overload in human and animal models increases oxidative stress and induces cardiomyopathy. It has been suggested that vasculature could be damaged by iron overload as well, but impacts on the vascular reactivity and the mechanisms enrolled have not been understood. In this study we aimed to identify possible changes in vascular reactivity of aorta from iron overloaded rats, investigating the underlying mechanisms. Rats were randomized and treated with iron dextran, i.p., 10mg/Kg/day or 100mg/kg/day five days a week for four weeks and compared to a saline injected group (control). Systolic blood pressure was measured weekly by tail cuff plethysmography. At the end of treatment, the blood iron parameters and iron deposition in tissues was assessed, and the vascular reactivity of the isolated aorta to phenylephrine, acetylcholine, sodium nitroprusside and angiotensin was analyzed in the context of endothelium denudation and incubation with L-NAME, tiron, catalase, apocynin, allopurinol, losartan, indomethacin or SQ 29598. Chronic iron administration increased serum iron and transferrin saturation with significant deposition in the liver. Additionally, high dose iron overload significantly increased the vasoconstrictor response in aortic rings as assessed in vitro, and endothelial denudation or L-NAME incubation have smaller impact on the vascular reactivity of the iron overloaded group, while these parameters have not changed in low dose iron overload group. Nitric oxide sensible fluorescent probe DAF-2 indicated reduced nitric oxide production in moderate iron overload when compared to controls. Iron overload-induced vascular hyperactivity was reversed by incubation with tiron, catalase, apocynin, allopurinol, losartan, indomethacin and SQ 29598. Moreover, malonyldialdehyde was elevated in plasma; and superoxide anion generation and NADPH oxidase membrane-bound subunit (p22phox) expression were increased in aorta from iron-loaded rats. Result demonstrated by the first time that chronic iron overload is associated with altered vascular reactivity with loss of endothelial modulation of the vascular tone. Moreover, the iron loading-induced endothelial dysfunction and reduced nitric oxide bioavailability may be a result of increased production of reactive oxygen species and local renin-angiotensin system and by way of cyclooxygenase activation.A sobrecarga de ferro no homem e em modelos animais aumenta o estresse oxidativo e induz cardiomiopatia. Tem sido sugerido que a vasculatura também poderia ser danificada pela sobrecarga de ferro, mas os impactos na reatividade vascular e os mecanismos envolvidos ainda não foram esclarecidos. Este estudo teve como objetivo identificar possíveis alterações na reatividade vascular de aorta de ratos submetidos à sobrecarga de ferro e investigar os mecanismos subjacentes. Os ratos foram randomizados e submetidos a injeções i.p. de ferro dextrano, 10 mg/kg/dia (sobrecarga de ferro branda) ou 100 mg/kg/dia (sobrecarga de ferro moderada), cinco dias por semana durante quatro semanas, e comparados com um grupo que recebeu injeções de solução salina (controle). A pressão arterial sistólica dos animais foi mensurada semanalmente pela pletismografia de cauda. No final do tratamento, os parâmetros de ferro sérico, deposição de ferro tecidual e a reatividade vascular da aorta à fenilefrina, acetilcolina, nitroprussiato de sódio e angiotensina II foi analisada, assim como a reatividade à fenilefrina com desnudação do endotélio e a incubação com L-NAME, tiron, catalase, apocinina, alopurinol, losartan, indometacina ou SQ 29598. Administração crônica de ferro aumentou a saturação da transferrina e níveis de ferro sérico, com deposição significativa no fígado. Além disso, a sobrecarga de ferro moderada aumentou significativamente a resposta vasoconstritora em anéis de aorta, avaliada in vitro, e a retirada do endotélio ou a incubação com L-NAME tiveram menor impacto sobre a reatividade vascular do grupo de sobrecarga de ferro, enquanto esses parâmetros não foram alterados no grupo sobrecarga de ferro branda. A sonda óxido nítrico-sensível DAF-2 indicou redução da produção de óxido nítrico na sobrecarga de ferro moderada quando comparado ao controle. A hiperreatividade vascular induzida pela sobrecarga de ferro foi revertida pela incubação com tiron, catalase, apocinina, alopurinol, losartan, indometacina e SQ 29598. Além disso, níveis de malondialdeido foram elevados no plasma; e geração de ânion superóxido e a expressão da subunidade de membrana da NADPH-oxidase (p22phox) foram aumentados na aorta de ratos submetidos à sobrecarga de ferro. Nossos resultados demonstram pela primeira vez que a sobrecarga de ferro crônica está associada à reatividade vascular alterada com perda de modulação endotelial do tônus vascular. Ademais, a sobrecarga de ferro induz disfunção endotelial e reduz a biodisponibilidade do óxido nítrico provavelmente devido ao aumento da produção de espécies reativas de oxigênio e ativação do sistema renina-angiotensina local e via da cicloxigenase.Texthttp://repositorio.ufes.br/handle/10/8008porUniversidade Federal do Espírito SantoMestrado em Ciências FisiológicasPrograma de Pós-Graduação em Ciências FisiológicasUFESBRCentro de Ciências da SaúdeIronVascular reactivityReactive oxygen speciesEndotheliumFerroAortaReatividade vascularEspécies reativas de oxigênioEndotélioFisiologia612Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFESORIGINALtese_9117_Dissertação Vinícius Bermond Marques.pdfapplication/pdf2984349http://repositorio.ufes.br/bitstreams/9e2e7081-6e51-4dfd-ab64-143cf0d468ec/download9b2815cc75a962ef20f57ca7e395e7b5MD5110/80082024-06-27 11:08:34.804oai:repositorio.ufes.br:10/8008http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-06-27T11:08:34Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false |
dc.title.none.fl_str_mv |
Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos |
title |
Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos |
spellingShingle |
Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos Marques, Vinícius Bermond Iron Vascular reactivity Reactive oxygen species Endothelium Ferro Aorta Reatividade vascular Espécies reativas de oxigênio Endotélio Fisiologia 612 |
title_short |
Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos |
title_full |
Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos |
title_fullStr |
Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos |
title_full_unstemmed |
Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos |
title_sort |
Efeitos da sobrecarga crônica de ferro sobre a reatividade vascular em aorta de ratos |
author |
Marques, Vinícius Bermond |
author_facet |
Marques, Vinícius Bermond |
author_role |
author |
dc.contributor.advisor-co1.fl_str_mv |
Graceli, Jones Bernardes |
dc.contributor.advisor1.fl_str_mv |
Santos, Leonardo dos |
dc.contributor.author.fl_str_mv |
Marques, Vinícius Bermond |
dc.contributor.referee1.fl_str_mv |
Xavier, Fabiano Elias |
dc.contributor.referee2.fl_str_mv |
Meyrelles, Silvana dos Santos |
contributor_str_mv |
Graceli, Jones Bernardes Santos, Leonardo dos Xavier, Fabiano Elias Meyrelles, Silvana dos Santos |
dc.subject.eng.fl_str_mv |
Iron Vascular reactivity Reactive oxygen species Endothelium |
topic |
Iron Vascular reactivity Reactive oxygen species Endothelium Ferro Aorta Reatividade vascular Espécies reativas de oxigênio Endotélio Fisiologia 612 |
dc.subject.por.fl_str_mv |
Ferro Aorta Reatividade vascular Espécies reativas de oxigênio Endotélio |
dc.subject.cnpq.fl_str_mv |
Fisiologia |
dc.subject.udc.none.fl_str_mv |
612 |
description |
Iron overload in human and animal models increases oxidative stress and induces cardiomyopathy. It has been suggested that vasculature could be damaged by iron overload as well, but impacts on the vascular reactivity and the mechanisms enrolled have not been understood. In this study we aimed to identify possible changes in vascular reactivity of aorta from iron overloaded rats, investigating the underlying mechanisms. Rats were randomized and treated with iron dextran, i.p., 10mg/Kg/day or 100mg/kg/day five days a week for four weeks and compared to a saline injected group (control). Systolic blood pressure was measured weekly by tail cuff plethysmography. At the end of treatment, the blood iron parameters and iron deposition in tissues was assessed, and the vascular reactivity of the isolated aorta to phenylephrine, acetylcholine, sodium nitroprusside and angiotensin was analyzed in the context of endothelium denudation and incubation with L-NAME, tiron, catalase, apocynin, allopurinol, losartan, indomethacin or SQ 29598. Chronic iron administration increased serum iron and transferrin saturation with significant deposition in the liver. Additionally, high dose iron overload significantly increased the vasoconstrictor response in aortic rings as assessed in vitro, and endothelial denudation or L-NAME incubation have smaller impact on the vascular reactivity of the iron overloaded group, while these parameters have not changed in low dose iron overload group. Nitric oxide sensible fluorescent probe DAF-2 indicated reduced nitric oxide production in moderate iron overload when compared to controls. Iron overload-induced vascular hyperactivity was reversed by incubation with tiron, catalase, apocynin, allopurinol, losartan, indomethacin and SQ 29598. Moreover, malonyldialdehyde was elevated in plasma; and superoxide anion generation and NADPH oxidase membrane-bound subunit (p22phox) expression were increased in aorta from iron-loaded rats. Result demonstrated by the first time that chronic iron overload is associated with altered vascular reactivity with loss of endothelial modulation of the vascular tone. Moreover, the iron loading-induced endothelial dysfunction and reduced nitric oxide bioavailability may be a result of increased production of reactive oxygen species and local renin-angiotensin system and by way of cyclooxygenase activation. |
publishDate |
2015 |
dc.date.issued.fl_str_mv |
2015-06-11 |
dc.date.accessioned.fl_str_mv |
2018-08-01T22:58:49Z |
dc.date.available.fl_str_mv |
2018-08-01 2018-08-01T22:58:49Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
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publishedVersion |
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http://repositorio.ufes.br/handle/10/8008 |
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http://repositorio.ufes.br/handle/10/8008 |
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por |
language |
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info:eu-repo/semantics/openAccess |
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openAccess |
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Text |
dc.publisher.none.fl_str_mv |
Universidade Federal do Espírito Santo Mestrado em Ciências Fisiológicas |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Ciências Fisiológicas |
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UFES |
dc.publisher.country.fl_str_mv |
BR |
dc.publisher.department.fl_str_mv |
Centro de Ciências da Saúde |
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Universidade Federal do Espírito Santo Mestrado em Ciências Fisiológicas |
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reponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) instname:Universidade Federal do Espírito Santo (UFES) instacron:UFES |
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Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
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