Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas
Autor(a) principal: | |
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Data de Publicação: | 2018 |
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/10/10578 |
Resumo: | Cardiovascular diseases represent the major cause of morbidity and mortality among women of the world and become more prevalent after menopause, which gives the estrogen cardioprotective role. Estrogenic hormone replacement therapy (HRT) alone or in combination with progestins has been the target of studies as an alternative potential in the management of conditions associated with the postmenopausal phase. In this context, medroxyprogesterone acetate (MPA) is the most studied and used progestin in HRT, but its actions on the cardiovascular system have demonstrated antagonistic effects to the benefits of progesterone, and drospirenone (DRSP) exerts a potent antimineralocorticoid action, clinical and experimental evidence of its positive performance. The renin-angiotensin system (RAS) is a key component in the control of cardiovascular homeostasis, which is modulated by the estrogenic condition, and thus, estrogen deficiency modulates this system unfavorably. The vascular effects of estrogen are well elucidated, but there is a shortage of studies investigating the effects of hormonal therapy with MPA and DRSP on the cardiovascular system. Since RAS is an important endocrine axis for the maintenance of cardiovascular hemodynamics and HRT is a therapeutic measure for the damages, symptoms and risks presented at menopause, it is necessary to know the effects of hormonal therapy with these progestins on this system. The experiments were conducted in Wistar sham and ovariectomized rats, which were randomly divided into 5 experimental groups: SHAM, ovariectomized (OVX), OVX treated with 17β-estradiol [E2] (OE2); OVX treated with DRSP and E2 (DRSP + OE2) and OVX treated with MPA (OVX + MPA) orally. After 4 weeks of treatment, vascular reactivity was performed with angiotensin-1-7 (Ang 1-7) dose-response curves, both alone and in the presence of the inhibitors L-NAME, PD123319 and A779.In addition, the aorta was dissected and the protein expression of AT-1, AT-2, MAS, ECA-2 and eNOS were evaluated. There was an increase in body weight of OVX and OVX + MPA animals, the efficacy of ovariectomy was confirmed by the reduction of the uterine weight of OVX rats and the hormone replacement treatments reversed this atrophy. There was an impairment in Ang 1-7-mediated aortic vascular reactivity in OVX rats, being prevented by the therapies, and OE2 rats improved this effect. Vasodilation was abolished in the presence of L-NAME and there was a reduction of the response in the presence of PD123319 in OE2 rats. There was no difference in the protein expression of AT1 and ECA-2 between the groups, Mas expression was higher in the OE2 and DRSP + OE2 and AT2 groups and eNOS was more expressed in OVX + MPA. In view of the abovementioned results, it can be concluded that hypoestrogenism impairs Ang 1-7 induced vasodilatation in vascular reactivity in aortic rings; and the therapies with estradiol and progestins restore these parameters, being this the first time that the effects of the hormonal therapies of MPA and DRSP + E2 on the vascular Ang 1-7 are reported. |
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Abreu, Glaucia Rodrigues deMenezes, Laís AlmeidaMauad, HelderRodrigues, Lívia Carla de Melo2018-12-20T13:25:50Z2018-12-202018-12-20T13:25:50Z2018-10-11Cardiovascular diseases represent the major cause of morbidity and mortality among women of the world and become more prevalent after menopause, which gives the estrogen cardioprotective role. Estrogenic hormone replacement therapy (HRT) alone or in combination with progestins has been the target of studies as an alternative potential in the management of conditions associated with the postmenopausal phase. In this context, medroxyprogesterone acetate (MPA) is the most studied and used progestin in HRT, but its actions on the cardiovascular system have demonstrated antagonistic effects to the benefits of progesterone, and drospirenone (DRSP) exerts a potent antimineralocorticoid action, clinical and experimental evidence of its positive performance. The renin-angiotensin system (RAS) is a key component in the control of cardiovascular homeostasis, which is modulated by the estrogenic condition, and thus, estrogen deficiency modulates this system unfavorably. The vascular effects of estrogen are well elucidated, but there is a shortage of studies investigating the effects of hormonal therapy with MPA and DRSP on the cardiovascular system. Since RAS is an important endocrine axis for the maintenance of cardiovascular hemodynamics and HRT is a therapeutic measure for the damages, symptoms and risks presented at menopause, it is necessary to know the effects of hormonal therapy with these progestins on this system. The experiments were conducted in Wistar sham and ovariectomized rats, which were randomly divided into 5 experimental groups: SHAM, ovariectomized (OVX), OVX treated with 17β-estradiol [E2] (OE2); OVX treated with DRSP and E2 (DRSP + OE2) and OVX treated with MPA (OVX + MPA) orally. After 4 weeks of treatment, vascular reactivity was performed with angiotensin-1-7 (Ang 1-7) dose-response curves, both alone and in the presence of the inhibitors L-NAME, PD123319 and A779.In addition, the aorta was dissected and the protein expression of AT-1, AT-2, MAS, ECA-2 and eNOS were evaluated. There was an increase in body weight of OVX and OVX + MPA animals, the efficacy of ovariectomy was confirmed by the reduction of the uterine weight of OVX rats and the hormone replacement treatments reversed this atrophy. There was an impairment in Ang 1-7-mediated aortic vascular reactivity in OVX rats, being prevented by the therapies, and OE2 rats improved this effect. Vasodilation was abolished in the presence of L-NAME and there was a reduction of the response in the presence of PD123319 in OE2 rats. There was no difference in the protein expression of AT1 and ECA-2 between the groups, Mas expression was higher in the OE2 and DRSP + OE2 and AT2 groups and eNOS was more expressed in OVX + MPA. In view of the abovementioned results, it can be concluded that hypoestrogenism impairs Ang 1-7 induced vasodilatation in vascular reactivity in aortic rings; and the therapies with estradiol and progestins restore these parameters, being this the first time that the effects of the hormonal therapies of MPA and DRSP + E2 on the vascular Ang 1-7 are reported.As doenças cardiovasculares representam a maior causa de morbimortalidade entre mulheres mundialmente e se tornam mais prevalentes após a menopausa, o que confere ao estrogênio papel cardioprotetor. A terapia de reposição hormonal (TRH) estrogênica isolada ou combinada com progestinas tem sido alvo de estudos como potencial alternativa na abordagem das condições associadas a fase pós-menopausa. Nesse contexto, o acetato de medroxiprogesterona (MPA) é a progestina mais estudada e utilizada na TRH, porém suas ações sobre o sistema cardiovascular têm demonstrado efeitos antagônicos aos benefícios da progesterona, e a drospirenona (DRSP) exerce uma potente ação antimineralocorticóide, havendo evidências clínicas e experimentais de sua atuação positiva.O sistema renina-angiotensina (SRA) é um componente-chave no controle da homeostase cardiovascular, o qual é modulado pela condição estrogênica, e sendo assim, a deficiência estrogênica modula desfavoravelmente esse sistema. Os efeitos vasculares do estrogênio são bem elucidados, porém há escassez de estudos que investiguem os efeitos da terapia hormonal com MPA e DRSP sobre o sistema cardiovascular. Sendo o SRA um importante eixo endócrino para a manutenção da hemodinâmica cardiovascular e a TRH uma medida terapêutica aos prejuízos, sintomas e riscos apresentados na menopausa, faz-se necessário conhecer os efeitos da terapia hormonal com essas progestinas sobre esse sistema.Os experimentos foram conduzidos em ratas Wistarsham e ovariectomizadas, as quais foram divididas aleatoriamente em 5 grupos experimentais: SHAM, ovariectomizadas (OVX), OVX tratadas com 17β-estradiol [E2] (OE2); OVX tratado com DRSP e E2 (DRSP+OE2) e OVX tratado com MPA (OVX+MPA) via oral. Após 4 semanas de tratamento, foi realizada a reatividade vascular, com curvas dose-resposta a angiotensina (1-7) (Ang 1-7), tanto sozinha quanto na presença dos inibidores L-NAME, PD123319 e A-779. Adicionalmente, a aorta foi dissecada e avaliada a expressão proteica de AT-1, AT-2, Mas, ECA-2 e eNOS. Houve um aumento de peso corporal dos animais OVX e OVX+MPA, a eficácia da ovariectomia foi comprovada com a redução do peso uterino das ratas OVX e os tratamentos de reposição hormonal reverteram essa atrofia. Houve um prejuízo na reatividade vascular aórtica mediada pela Ang 1-7 nas ratas OVX, sendo prevenido pelas terapias, sendo que as ratas OE2 melhoraram esse efeito. A vasodilatação foi abolida na presença de L-NAME e houve redução da resposta na presença de PD123319 nas ratas OE2. Não houve diferença na expressão proteica de AT1 e ECA-2 entre os grupos, a expressão de Mas foi maior nos grupos OE2 e DRSP+OE2 e AT2 e eNOS foi mais expressa em OVX+MPA. Diante dos resultados expostos, pode-se concluir que a hipoestrogenia prejudica a vasodilatação induzida pela Ang 1-7 na reatividade vascular em anéis aórticos; as terapias com estradiol e progestinas restauram esses parâmetros, sendo esta a primeira vez que são relatados os efeitos das terapias hormonais de MPA e DRSP+E2 sobre a Ang 1-7 vascular.Texthttp://repositorio.ufes.br/handle/10/10578porUniversidade Federal do Espírito SantoMestrado em Ciências FisiológicasPrograma de Pós-Graduação em Ciências FisiológicasUFESBRCentro de Ciências da SaúdeDeficiency estrogenousRenin-angiotensin systemTherapy hormonal replaceAcetate of medroxyprogesteroneDrospirenoneDeficiência estrogênicaSistema renina-angiotensinaTerapia de reposição hormonal17β-estradiolAcetato de medroxiprogesteronaDrospirenonaEstrógenosMenopausa - HormonoterapiaFisiologia612Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadasinfo: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_12642_Dissertação Laís Almeida Menezes.pdfapplication/pdf882715http://repositorio.ufes.br/bitstreams/c46df9d1-6421-4ff0-9dab-6d85798130a6/download34ae923525e56c73f2a72805f180ebe2MD5110/105782024-06-27 11:04:26.224oai:repositorio.ufes.br:10/10578http://repositorio.ufes.brRepositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestopendoar:21082024-06-27T11:04:26Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false |
dc.title.none.fl_str_mv |
Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas |
title |
Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas |
spellingShingle |
Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas Menezes, Laís Almeida Deficiency estrogenous Renin-angiotensin system Therapy hormonal replace Acetate of medroxyprogesterone Drospirenone Deficiência estrogênica Sistema renina-angiotensina Terapia de reposição hormonal 17β-estradiol Acetato de medroxiprogesterona Drospirenona Fisiologia Estrógenos Menopausa - Hormonoterapia 612 |
title_short |
Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas |
title_full |
Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas |
title_fullStr |
Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas |
title_full_unstemmed |
Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas |
title_sort |
Efeitos da terapia de reposição hormonal com estradiol e progestinas sobre o sistema renina-angiostensina vascular de ratas ovariectomizadas |
author |
Menezes, Laís Almeida |
author_facet |
Menezes, Laís Almeida |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Abreu, Glaucia Rodrigues de |
dc.contributor.author.fl_str_mv |
Menezes, Laís Almeida |
dc.contributor.referee1.fl_str_mv |
Mauad, Helder |
dc.contributor.referee2.fl_str_mv |
Rodrigues, Lívia Carla de Melo |
contributor_str_mv |
Abreu, Glaucia Rodrigues de Mauad, Helder Rodrigues, Lívia Carla de Melo |
dc.subject.eng.fl_str_mv |
Deficiency estrogenous Renin-angiotensin system Therapy hormonal replace Acetate of medroxyprogesterone Drospirenone |
topic |
Deficiency estrogenous Renin-angiotensin system Therapy hormonal replace Acetate of medroxyprogesterone Drospirenone Deficiência estrogênica Sistema renina-angiotensina Terapia de reposição hormonal 17β-estradiol Acetato de medroxiprogesterona Drospirenona Fisiologia Estrógenos Menopausa - Hormonoterapia 612 |
dc.subject.por.fl_str_mv |
Deficiência estrogênica Sistema renina-angiotensina Terapia de reposição hormonal 17β-estradiol Acetato de medroxiprogesterona Drospirenona |
dc.subject.cnpq.fl_str_mv |
Fisiologia |
dc.subject.br-rjbn.none.fl_str_mv |
Estrógenos Menopausa - Hormonoterapia |
dc.subject.udc.none.fl_str_mv |
612 |
description |
Cardiovascular diseases represent the major cause of morbidity and mortality among women of the world and become more prevalent after menopause, which gives the estrogen cardioprotective role. Estrogenic hormone replacement therapy (HRT) alone or in combination with progestins has been the target of studies as an alternative potential in the management of conditions associated with the postmenopausal phase. In this context, medroxyprogesterone acetate (MPA) is the most studied and used progestin in HRT, but its actions on the cardiovascular system have demonstrated antagonistic effects to the benefits of progesterone, and drospirenone (DRSP) exerts a potent antimineralocorticoid action, clinical and experimental evidence of its positive performance. The renin-angiotensin system (RAS) is a key component in the control of cardiovascular homeostasis, which is modulated by the estrogenic condition, and thus, estrogen deficiency modulates this system unfavorably. The vascular effects of estrogen are well elucidated, but there is a shortage of studies investigating the effects of hormonal therapy with MPA and DRSP on the cardiovascular system. Since RAS is an important endocrine axis for the maintenance of cardiovascular hemodynamics and HRT is a therapeutic measure for the damages, symptoms and risks presented at menopause, it is necessary to know the effects of hormonal therapy with these progestins on this system. The experiments were conducted in Wistar sham and ovariectomized rats, which were randomly divided into 5 experimental groups: SHAM, ovariectomized (OVX), OVX treated with 17β-estradiol [E2] (OE2); OVX treated with DRSP and E2 (DRSP + OE2) and OVX treated with MPA (OVX + MPA) orally. After 4 weeks of treatment, vascular reactivity was performed with angiotensin-1-7 (Ang 1-7) dose-response curves, both alone and in the presence of the inhibitors L-NAME, PD123319 and A779.In addition, the aorta was dissected and the protein expression of AT-1, AT-2, MAS, ECA-2 and eNOS were evaluated. There was an increase in body weight of OVX and OVX + MPA animals, the efficacy of ovariectomy was confirmed by the reduction of the uterine weight of OVX rats and the hormone replacement treatments reversed this atrophy. There was an impairment in Ang 1-7-mediated aortic vascular reactivity in OVX rats, being prevented by the therapies, and OE2 rats improved this effect. Vasodilation was abolished in the presence of L-NAME and there was a reduction of the response in the presence of PD123319 in OE2 rats. There was no difference in the protein expression of AT1 and ECA-2 between the groups, Mas expression was higher in the OE2 and DRSP + OE2 and AT2 groups and eNOS was more expressed in OVX + MPA. In view of the abovementioned results, it can be concluded that hypoestrogenism impairs Ang 1-7 induced vasodilatation in vascular reactivity in aortic rings; and the therapies with estradiol and progestins restore these parameters, being this the first time that the effects of the hormonal therapies of MPA and DRSP + E2 on the vascular Ang 1-7 are reported. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-12-20T13:25:50Z |
dc.date.available.fl_str_mv |
2018-12-20 2018-12-20T13:25:50Z |
dc.date.issued.fl_str_mv |
2018-10-11 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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Universidade Federal do Espírito Santo Mestrado em Ciências Fisiológicas |
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Programa de Pós-Graduação em Ciências Fisiológicas |
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UFES |
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BR |
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Centro de Ciências da Saúde |
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Universidade Federal do Espírito Santo Mestrado em Ciências Fisiológicas |
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Universidade Federal do Espírito Santo (UFES) |
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UFES |
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UFES |
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Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
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Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) |
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