Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar

Bibliographic Details
Main Author: Rouver, Wender do Nascimento
Publication Date: 2015
Format: Master thesis
Language: por
Source: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
Download full: http://repositorio.ufes.br/handle/10/8003
Summary: Cardiovascular diseases are the leading cause of death in world and the fact that men are more affected meant that the testosterone was thought of as a harmful substance to the cardiovascular system. However, more recent studies have challenged this hypothesis and suggest a beneficial role of this hormone on the cardiovascular system. Nevertheless, the effects of chronic testosterone treatment on vascular endothelium-dependent function, have not been fully clarified. Thus, the present study was designed to determine the effects of chronic treatment with different doses of testosterone on coronary vascular reactivity induced by bradykinin. Males Wistar rats were used with 10 weeks of age, who were separated in Sham and castrated groups. Castrated rats were immediately treated with physiological (Physio, 0.5 mg / kg / day, sc) and supraphysiological (Supra, 2.5 mg / kg / day, sc) doses of testosterone for 15 days. Systolic blood pressure (SBP) was measured by tail plethysmography at the end of treatment. After euthanasia, the hearts were removed and coronary vascular reactivity was assessed by retrograde perfusion technique Langendorff. Dose response curve of bradykinin (BK) was then constructed by inhibition with 100 mM L-NAME, 2.8 uM indomethacin (INDO), L-NAME + INDO or L-NAME + INDO + 0.75 uM clotrimazole (CLOT). Data were expressed as mean ± SEM and the comparison between groups was performed by one or two-way ANOVA followed by the post-hoc Tukey test (p <0.05). We observed significant coronary endothelium-dependent vasodilation induced by BK, which was abolished in castrated group and restored in Physio and Supra group. After conjugated inhibition of endothelium-dependent relaxation factors (NO, PGI2 and EDHF), we found that vasodilation was abolished in all groups. Castration modulated lipid and hormonal profile, as well as reduced body weight and replacement with testosterone was able to restore all of these parameters. We also observed a significant increase in blood pressure in Supra group. Our data lead us to conclude that testosterone physiological concentrations may play a beneficial role in cardiovascular system to maintain a favorable environment for the action of an endothelium-dependent vasodilator, with no increase in SBP, which makes this steroid a possible tool in hormone therapies.
id UFES_f32fbdc8e9d315739b7c6b83ed1fdd5e
oai_identifier_str oai:repositorio.ufes.br:10/8003
network_acronym_str UFES
network_name_str Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
repository_id_str 2108
spelling Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistarCoronary arteriesTestosteroneHormone replacementEndotheliumVasodilatationArtérias coronáriasTestosteronaReposição hormonalEndotélioVasodilataçãoFisiologia612Cardiovascular diseases are the leading cause of death in world and the fact that men are more affected meant that the testosterone was thought of as a harmful substance to the cardiovascular system. However, more recent studies have challenged this hypothesis and suggest a beneficial role of this hormone on the cardiovascular system. Nevertheless, the effects of chronic testosterone treatment on vascular endothelium-dependent function, have not been fully clarified. Thus, the present study was designed to determine the effects of chronic treatment with different doses of testosterone on coronary vascular reactivity induced by bradykinin. Males Wistar rats were used with 10 weeks of age, who were separated in Sham and castrated groups. Castrated rats were immediately treated with physiological (Physio, 0.5 mg / kg / day, sc) and supraphysiological (Supra, 2.5 mg / kg / day, sc) doses of testosterone for 15 days. Systolic blood pressure (SBP) was measured by tail plethysmography at the end of treatment. After euthanasia, the hearts were removed and coronary vascular reactivity was assessed by retrograde perfusion technique Langendorff. Dose response curve of bradykinin (BK) was then constructed by inhibition with 100 mM L-NAME, 2.8 uM indomethacin (INDO), L-NAME + INDO or L-NAME + INDO + 0.75 uM clotrimazole (CLOT). Data were expressed as mean ± SEM and the comparison between groups was performed by one or two-way ANOVA followed by the post-hoc Tukey test (p <0.05). We observed significant coronary endothelium-dependent vasodilation induced by BK, which was abolished in castrated group and restored in Physio and Supra group. After conjugated inhibition of endothelium-dependent relaxation factors (NO, PGI2 and EDHF), we found that vasodilation was abolished in all groups. Castration modulated lipid and hormonal profile, as well as reduced body weight and replacement with testosterone was able to restore all of these parameters. We also observed a significant increase in blood pressure in Supra group. Our data lead us to conclude that testosterone physiological concentrations may play a beneficial role in cardiovascular system to maintain a favorable environment for the action of an endothelium-dependent vasodilator, with no increase in SBP, which makes this steroid a possible tool in hormone therapies.As doenças cardiovasculares lideram a causa de morte mundial e o fato dos homens serem mais acometidos fizeram com que a testosterona fosse pensada como uma substância deletéria ao sistema cardiovascular. Contudo, estudos mais recentes contestam essa hipótese e sugerem um papel benéfico desse hormônio sobre o sistema cardiovascular. Não obstante, os efeitos do tratamento crônico com testosterona sobre a função vascular dependente do endotélio, ainda não foram totalmente esclarecidos. Diante disso, o presente estudo foi desenvolvido para determinar os efeitos do tratamento crônico com diferentes doses de testosterona sobre a reatividade vascular coronariana induzida pela bradicinina. Foram utilizados ratos Wistar, machos, com 10 semanas de idade, que foram separados em grupos Sham e Castrados. Os animais castrados foram imediatamente tratados com doses fisiológica (Fisio, 0,5 mg/Kg/dia, sc) e suprafisiológica (Supra, 2,5 mg/Kg/dia, sc) de testosterona por 15 dias. A pressão arterial sistólica (PAS) foi avaliada por pletismografia de cauda, ao final do tratamento. Após eutanásia os corações foram removidos e a reatividade vascular coronariana foi avaliada pela técnica de perfusão retrograda de Langendorff. Curva dose resposta de bradicinina (BK) foi construída seguida por inibições com 100 μM L-NAME, 2,8 μM indometacina (INDO), L-NAME + INDO ou L-NAME + INDO + 0,75 μM clotrimazol (CLOT). Os dados foram expressos como média ± EPM e a comparação entre os grupos foi realizada por ANOVA de 1 ou 2 vias seguidos do post-hoc de Tukey (p < 0,05). Observamos significante vasodilatação coronariana dependente do endotélio, induzida pela BK, que foi abolida no grupo castrado e restaurada no grupo Fisio e Supra. Após inibição conjugada dos fatores de relaxamento dependente do endotélio (NO, PGI2 e EDHF), observamos que a vasodilatação foi abolida em todos os grupos. A castração modulou o perfil lipídico e hormonal, bem como reduziu o peso corporal e a reposição com testosterona foi capaz de restaurar todos esses parâmetros. Observamos ainda aumento significante dos níveis pressóricos no grupo Supra. Nossos dados nos levam a concluir que concentrações fisiológicas de testosterona podem exercer um papel benéfico ao sistema cardiovascular por manter um ambiente favorável à ação de um vasodilatador dependente do endotélio, sem aumento de PAS, o que faz desse esteroide uma possível ferramenta em terapias hormonais.Universidade Federal do Espírito SantoBRMestrado em Ciências FisiológicasCentro de Ciências da SaúdeUFESPrograma de Pós-Graduação em Ciências FisiológicasSantos, Roger Lyrio dosMoyses, Margareth RibeiroAndrade, Tadeu Uggere deGraceli, Jones BernardesRouver, Wender do Nascimento2018-08-01T22:58:48Z2018-08-012018-08-01T22:58:48Z2015-01-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisTextapplication/pdfhttp://repositorio.ufes.br/handle/10/8003porinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)instname:Universidade Federal do Espírito Santo (UFES)instacron:UFES2024-07-16T17:10:08Zoai:repositorio.ufes.br:10/8003Repositório InstitucionalPUBhttp://repositorio.ufes.br/oai/requestriufes@ufes.bropendoar:21082024-07-16T17:10:08Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)false
dc.title.none.fl_str_mv Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar
title Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar
spellingShingle Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar
Rouver, Wender do Nascimento
Coronary arteries
Testosterone
Hormone replacement
Endothelium
Vasodilatation
Artérias coronárias
Testosterona
Reposição hormonal
Endotélio
Vasodilatação
Fisiologia
612
title_short Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar
title_full Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar
title_fullStr Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar
title_full_unstemmed Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar
title_sort Efeitos cardiovasculares do tratamento crônico com testosterona em ratos wistar
author Rouver, Wender do Nascimento
author_facet Rouver, Wender do Nascimento
author_role author
dc.contributor.none.fl_str_mv Santos, Roger Lyrio dos
Moyses, Margareth Ribeiro
Andrade, Tadeu Uggere de
Graceli, Jones Bernardes
dc.contributor.author.fl_str_mv Rouver, Wender do Nascimento
dc.subject.por.fl_str_mv Coronary arteries
Testosterone
Hormone replacement
Endothelium
Vasodilatation
Artérias coronárias
Testosterona
Reposição hormonal
Endotélio
Vasodilatação
Fisiologia
612
topic Coronary arteries
Testosterone
Hormone replacement
Endothelium
Vasodilatation
Artérias coronárias
Testosterona
Reposição hormonal
Endotélio
Vasodilatação
Fisiologia
612
description Cardiovascular diseases are the leading cause of death in world and the fact that men are more affected meant that the testosterone was thought of as a harmful substance to the cardiovascular system. However, more recent studies have challenged this hypothesis and suggest a beneficial role of this hormone on the cardiovascular system. Nevertheless, the effects of chronic testosterone treatment on vascular endothelium-dependent function, have not been fully clarified. Thus, the present study was designed to determine the effects of chronic treatment with different doses of testosterone on coronary vascular reactivity induced by bradykinin. Males Wistar rats were used with 10 weeks of age, who were separated in Sham and castrated groups. Castrated rats were immediately treated with physiological (Physio, 0.5 mg / kg / day, sc) and supraphysiological (Supra, 2.5 mg / kg / day, sc) doses of testosterone for 15 days. Systolic blood pressure (SBP) was measured by tail plethysmography at the end of treatment. After euthanasia, the hearts were removed and coronary vascular reactivity was assessed by retrograde perfusion technique Langendorff. Dose response curve of bradykinin (BK) was then constructed by inhibition with 100 mM L-NAME, 2.8 uM indomethacin (INDO), L-NAME + INDO or L-NAME + INDO + 0.75 uM clotrimazole (CLOT). Data were expressed as mean ± SEM and the comparison between groups was performed by one or two-way ANOVA followed by the post-hoc Tukey test (p <0.05). We observed significant coronary endothelium-dependent vasodilation induced by BK, which was abolished in castrated group and restored in Physio and Supra group. After conjugated inhibition of endothelium-dependent relaxation factors (NO, PGI2 and EDHF), we found that vasodilation was abolished in all groups. Castration modulated lipid and hormonal profile, as well as reduced body weight and replacement with testosterone was able to restore all of these parameters. We also observed a significant increase in blood pressure in Supra group. Our data lead us to conclude that testosterone physiological concentrations may play a beneficial role in cardiovascular system to maintain a favorable environment for the action of an endothelium-dependent vasodilator, with no increase in SBP, which makes this steroid a possible tool in hormone therapies.
publishDate 2015
dc.date.none.fl_str_mv 2015-01-02
2018-08-01T22:58:48Z
2018-08-01
2018-08-01T22:58:48Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufes.br/handle/10/8003
url http://repositorio.ufes.br/handle/10/8003
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv Text
application/pdf
dc.publisher.none.fl_str_mv Universidade Federal do Espírito Santo
BR
Mestrado em Ciências Fisiológicas
Centro de Ciências da Saúde
UFES
Programa de Pós-Graduação em Ciências Fisiológicas
publisher.none.fl_str_mv Universidade Federal do Espírito Santo
BR
Mestrado em Ciências Fisiológicas
Centro de Ciências da Saúde
UFES
Programa de Pós-Graduação em Ciências Fisiológicas
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
instname:Universidade Federal do Espírito Santo (UFES)
instacron:UFES
instname_str Universidade Federal do Espírito Santo (UFES)
instacron_str UFES
institution UFES
reponame_str Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
collection Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
repository.name.fl_str_mv Repositório Institucional da Universidade Federal do Espírito Santo (riUfes) - Universidade Federal do Espírito Santo (UFES)
repository.mail.fl_str_mv riufes@ufes.br
_version_ 1834478863779889152