Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos

Detalhes bibliográficos
Autor(a) principal: Miotto, Danyelle Siqueira
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/11513
Resumo: Hypertension (HT) is a complex and multifactorial disease considered one of the main risk factor for cardiovascular diseases. It is maintained mainly by structural changes in vessels that contribute to increase vascular resistance. Changes in the intrinsic elastic properties of the vessel wall contribute to determine arterial stiffness and may compromise vessel functioning. Currently, arterial stiffness has been considered an important predictor of cardiovascular mortality. Among the antihypertensive treatments, angiotensin converting enzyme inhibitors (ACEi) have been used to improve vessel compliance, however, almost nothing is known about the use of ACEi, associated or not with aerobic TF, on the improvement of arterial stiffness in hypertensive animals. We hypothesized that T associated with perindopril could improve arterial stiffness and HT higher than isolated treatments. Therefore, the aim of this study was to investigate the effects of aerobic T, associated or not with perindopril treatment on arterial stiffness, arterial pressure and cardiac remodeling in spontaneously hypertensive rats (SHR). 49 SHR (200-300g) were randomly allocated into 4 groups: 1 / sedentary control (SC, n = 12) 2 / sedentary treated with perindopril (SP, n = 10, 3 mg / kg per day, by gavage) 3 / trained control (TC, n = 13, which underwent treadmill aerobic exercise per 60 days), 4 / trained perindopril (TP, n = 14, which underwent aerobic TF and were treated with perindopril). Ten wistar rats were used as normotensive control. Weekly tail pressure measurements were measured. At the end of experimental protocol, pulse wave velocity (PWV) was performed to analyze arterial stiffness. After measurement of direct arterial pressure (AP), autonomic balance and barroreflex analysis, aorta artery was removed for proteomic analysis and muscle tissues (soleus and left ventricle) for histological analyses. The sedentary hypertensive rats (SC) presented lower body weight (-26.51%) and lower SOL weight (-26%) compared to wistar rats. However, hemodynamic values of SBP, DBP and MAP were elevated (+ 69.61%, 62.33% and 63.53% respectively), as well as VOP (+ 49.35%) and sympathetic nerve activity for vessels (+ 64.33%) when compared to wistar. Spontaneous (non-pharmacological) barroreflex analysis of SC had values of reflex bradycardia (GAIN UP, -43.70%), as well as the sum of reduced reflex bradycardia and reflex tachycardia (GAIN ALL, -42.47%), when compared to wistar. The histological analysis of collagen density was increased (+ 136.80%) in SC rats, whereas C: F (+ 24.34%) was higher in wistar. PWV was higher and treatment with perindopril and / or T were able to reduce it in SHR (-36%, -21% and -46%, for SP, TF and TP, respectively), compared with SC. Media wall AST values were also reduced in the SP (-59%), TC (-55%) and TP (-44%) groups, compared with SC. In addition, LV collagen density was reduced after perindopril (-53%), T (-46%) and its association (-52%). Only trained groups presented higher values of capillary-to-fiber ratio (64% and 37%, for TC and TP respectively). Sympathetic nervous activity to the vessels was also reduced only after T. Proteomic analysis suggested that some proteins that were up regulated after perindopril, were contra balanced by T, through different pathways. Results of this study suggest that reduction of arterial stiffness induced by T maybe associated with renin angiontensin system, since reduction were similar to those after perindopril treatment. Besides functional responses were similar, proteomic results suggest that both strategies act through different protein pathway. Improvements of arterial stiffness may be also associated with local and neural skeletal muscle microcirculation alterationsand both treatments did not determine synergic responses.
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spelling Miotto, Danyelle SiqueiraCardoso, Sandra Lia do Amaralhttp://lattes.cnpq.br/2030708742766455http://lattes.cnpq.br/06012610667491632019-07-17T13:18:22Z2019-07-17T13:18:22Z2019-03-27MIOTTO, Danyelle Siqueira. Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos. 2019. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11513.https://repositorio.ufscar.br/handle/ufscar/11513Hypertension (HT) is a complex and multifactorial disease considered one of the main risk factor for cardiovascular diseases. It is maintained mainly by structural changes in vessels that contribute to increase vascular resistance. Changes in the intrinsic elastic properties of the vessel wall contribute to determine arterial stiffness and may compromise vessel functioning. Currently, arterial stiffness has been considered an important predictor of cardiovascular mortality. Among the antihypertensive treatments, angiotensin converting enzyme inhibitors (ACEi) have been used to improve vessel compliance, however, almost nothing is known about the use of ACEi, associated or not with aerobic TF, on the improvement of arterial stiffness in hypertensive animals. We hypothesized that T associated with perindopril could improve arterial stiffness and HT higher than isolated treatments. Therefore, the aim of this study was to investigate the effects of aerobic T, associated or not with perindopril treatment on arterial stiffness, arterial pressure and cardiac remodeling in spontaneously hypertensive rats (SHR). 49 SHR (200-300g) were randomly allocated into 4 groups: 1 / sedentary control (SC, n = 12) 2 / sedentary treated with perindopril (SP, n = 10, 3 mg / kg per day, by gavage) 3 / trained control (TC, n = 13, which underwent treadmill aerobic exercise per 60 days), 4 / trained perindopril (TP, n = 14, which underwent aerobic TF and were treated with perindopril). Ten wistar rats were used as normotensive control. Weekly tail pressure measurements were measured. At the end of experimental protocol, pulse wave velocity (PWV) was performed to analyze arterial stiffness. After measurement of direct arterial pressure (AP), autonomic balance and barroreflex analysis, aorta artery was removed for proteomic analysis and muscle tissues (soleus and left ventricle) for histological analyses. The sedentary hypertensive rats (SC) presented lower body weight (-26.51%) and lower SOL weight (-26%) compared to wistar rats. However, hemodynamic values of SBP, DBP and MAP were elevated (+ 69.61%, 62.33% and 63.53% respectively), as well as VOP (+ 49.35%) and sympathetic nerve activity for vessels (+ 64.33%) when compared to wistar. Spontaneous (non-pharmacological) barroreflex analysis of SC had values of reflex bradycardia (GAIN UP, -43.70%), as well as the sum of reduced reflex bradycardia and reflex tachycardia (GAIN ALL, -42.47%), when compared to wistar. The histological analysis of collagen density was increased (+ 136.80%) in SC rats, whereas C: F (+ 24.34%) was higher in wistar. PWV was higher and treatment with perindopril and / or T were able to reduce it in SHR (-36%, -21% and -46%, for SP, TF and TP, respectively), compared with SC. Media wall AST values were also reduced in the SP (-59%), TC (-55%) and TP (-44%) groups, compared with SC. In addition, LV collagen density was reduced after perindopril (-53%), T (-46%) and its association (-52%). Only trained groups presented higher values of capillary-to-fiber ratio (64% and 37%, for TC and TP respectively). Sympathetic nervous activity to the vessels was also reduced only after T. Proteomic analysis suggested that some proteins that were up regulated after perindopril, were contra balanced by T, through different pathways. Results of this study suggest that reduction of arterial stiffness induced by T maybe associated with renin angiontensin system, since reduction were similar to those after perindopril treatment. Besides functional responses were similar, proteomic results suggest that both strategies act through different protein pathway. Improvements of arterial stiffness may be also associated with local and neural skeletal muscle microcirculation alterationsand both treatments did not determine synergic responses.A hipertensão arterial (HA) é uma doença complexa e multifatorial, considerada um dos principais fatores de risco de doenças cardiovasculares. Em sua fase crônica, é mantida principalmente por alterações estruturais nos vasos que contribuem para aumentar a resistência vascular. As alterações nas propriedades elásticas intrínsecas da parede do vaso contribuem para determinar a rigidez arterial, a qual vem sendo considerada um importante preditor de mortalidade cardiovascular. Os inibidores da enzima conversora de angiotensina (iECA) vêm sendo utilizados para melhorar a complacência dos vasos, no entanto, pouco se sabe sobre o uso dos iECA, associados ou não ao treinamento físico (TF) aeróbio, na melhora da rigidez arterial em animais hipertensos. A hipótese deste estudo foi que o TF, associado ao tratamento com perindopril, poderia melhorar a rigidez arterial e a pressão arterial (PA) dos SHR, quando comparados aos tratamentos isolados. O objetivo geral desse trabalho foi verificar os mecanismos induzidos pelo TF aeróbio, associado ou não ao tratamento com perindopril que podem contribuir para o remodelamento da aorta e do VE de SHR e, consequentemente, melhorar rigidez arterial e pressão arterial. Foram utilizados 49 SHR (200-300g) separados aleatoriamente em 4 grupos: 1/ sedentário controle (SC, n=12) 2/ sedentário perindopril (SP, n=10, sedentários e tratados com perindopril, 3mg/kg por dia, via gavagem) 3/ treinados controle (TC, n=13, submetidos a TF aeróbio em esteira por 60 dias), 4/ treinado perindopril (TP, n=14, submetidos a TF aeróbio e tratados com perindopril). Todos os grupos controles receberam tratamento com água e 10 ratos Wistar foram usados com controle normotenso. Semanalmente foi aferida a pressão arterial de cauda dos ratos. A rigidez arterial foi avaliada pela medida de velocidade de onda de pulso (VOP). Após análises de PA direta, do balanço autonômico e barroreflexo espontâneo, a artéria aorta foi retirada para análise proteômica e os tecidos musculares (sóleo, SOL e ventrículo esquerdo, VE) para as análises histológicas. Os SHR sedentários (SC), apresentavam peso corporal (-26,51%) e o peso do SOL (-26%) menor quando comparados aos ratos wistar, entretanto os valores de PAS, PAD e PAM encontravam-se elevados (+69,61, 62,33% e 63,53% respetivamente). Da mesma forma, a VOP (+49,35%) e a atividade nervosa simpática para os vasos (+64,33%) era maior quando comparadas com os wistar. Os SC apresentavam menores valores de efetividade de bradicardia reflexa (GAIN UP , -43,70%) e da somatória das respotas de bradicardia e taquicardia reflexas (GAIN ALL, -42,47%), quando comparado com os wistar. A densidade de colágeno encontrava-se aumentada (+136,80%) nos ratos SC, enquanto que a razão C:F (+24,34%) se apresentava maior nos wistar. A VOP estava aumentada nos SHR e o tratamento com perindopril e/ou o TF foram eficazes em reduzí-la (-36%, -21% e -46%, para SP, TC e TP, respectivamente, p<0,05), comparados ao SC. Os valores de AST da camada média das arteríolas da musculatura esquelética também estavam menores nos grupos SP (-59%), TC (-55 %) e TP (-44%), comparados ao SC. Adicionalmente, a densidade de colágeno no VE dos SHR também estava reduzida após tratamento com perindopril (-53%), TF (-46%) ou associação (-52%). Somente os grupos treinados apresentaram maior razão de capilares/fibras (+63,57% e +36,52%, para TC e TP respectivamente). A atividade nervosa simpática para os vasos estava menor nos grupos treinados. A análise proteômica permitiu sugerir que algumas proteínas que estavam suprareguladas pelo tratamento farmacológico foram contrabalanceadas pelo TF, por vias diferentes. Os principais resultados desse estudo sugerem que a melhora da rigidez arterial após TF aeróbio parece estar associada com uma redução da atividade do sistema renina angiotensina, uma vez que os resultados foram semelhantes aqueles encontrados após tratamento com perindopril. Apesar das respostas funcionais serem semelhantes, os resultados da proteômica sugerem que os diferentes tratamentos modulam vias diferentes de proteínas. A redução de rigidez arterial parece estar também associada com alterações locais e neurais presentes na microcirculação da musculatura esquelética e a associação das duas estratégias não apresentou efeito sinérgico na redução da VOP ou PA nos SHR, no entanto, somente os animais treinados apresentaram angiogênese na musculatura esquelética.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)CAPES : 1692103FAPESP : 2017/00509-1porUniversidade Federal de São CarlosCâmpus São CarlosPrograma Interinstitucional de Pós-Graduação em Ciências Fisiológicas - PIPGCFUFSCarInibidores da ECAVelocidade de onda de pulsoExercício físicoHipertensão arterialACE inhibitorsPulse wave velocityPhysical training/exerciseHypertensionCIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMASOs efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensosEffects of physical training, associated with perindopril, on arterial stiffness of spontaneously hypertensive ratsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisOnlineinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALDEFESA.VERSÃO.REPOSITÓRIO.pdfDEFESA.VERSÃO.REPOSITÓRIO.pdfDocumento de Dissertaçãoapplication/pdf4817746https://{{ getenv "DSPACE_HOST" "repositorio.ufscar.br" }}/bitstream/ufscar/11513/4/DEFESA.VERS%c3%83O.REPOSIT%c3%93RIO.pdffe5ee1089e7336c8c44463dd79a73787MD54LICENSElicense.txtlicense.txttext/plain; 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dc.title.por.fl_str_mv Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos
dc.title.alternative.eng.fl_str_mv Effects of physical training, associated with perindopril, on arterial stiffness of spontaneously hypertensive rats
title Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos
spellingShingle Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos
Miotto, Danyelle Siqueira
Inibidores da ECA
Velocidade de onda de pulso
Exercício físico
Hipertensão arterial
ACE inhibitors
Pulse wave velocity
Physical training/exercise
Hypertension
CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS
title_short Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos
title_full Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos
title_fullStr Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos
title_full_unstemmed Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos
title_sort Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos
author Miotto, Danyelle Siqueira
author_facet Miotto, Danyelle Siqueira
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/0601261066749163
dc.contributor.author.fl_str_mv Miotto, Danyelle Siqueira
dc.contributor.advisor1.fl_str_mv Cardoso, Sandra Lia do Amaral
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2030708742766455
contributor_str_mv Cardoso, Sandra Lia do Amaral
dc.subject.por.fl_str_mv Inibidores da ECA
Velocidade de onda de pulso
Exercício físico
Hipertensão arterial
topic Inibidores da ECA
Velocidade de onda de pulso
Exercício físico
Hipertensão arterial
ACE inhibitors
Pulse wave velocity
Physical training/exercise
Hypertension
CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS
dc.subject.eng.fl_str_mv ACE inhibitors
Pulse wave velocity
Physical training/exercise
Hypertension
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS
description Hypertension (HT) is a complex and multifactorial disease considered one of the main risk factor for cardiovascular diseases. It is maintained mainly by structural changes in vessels that contribute to increase vascular resistance. Changes in the intrinsic elastic properties of the vessel wall contribute to determine arterial stiffness and may compromise vessel functioning. Currently, arterial stiffness has been considered an important predictor of cardiovascular mortality. Among the antihypertensive treatments, angiotensin converting enzyme inhibitors (ACEi) have been used to improve vessel compliance, however, almost nothing is known about the use of ACEi, associated or not with aerobic TF, on the improvement of arterial stiffness in hypertensive animals. We hypothesized that T associated with perindopril could improve arterial stiffness and HT higher than isolated treatments. Therefore, the aim of this study was to investigate the effects of aerobic T, associated or not with perindopril treatment on arterial stiffness, arterial pressure and cardiac remodeling in spontaneously hypertensive rats (SHR). 49 SHR (200-300g) were randomly allocated into 4 groups: 1 / sedentary control (SC, n = 12) 2 / sedentary treated with perindopril (SP, n = 10, 3 mg / kg per day, by gavage) 3 / trained control (TC, n = 13, which underwent treadmill aerobic exercise per 60 days), 4 / trained perindopril (TP, n = 14, which underwent aerobic TF and were treated with perindopril). Ten wistar rats were used as normotensive control. Weekly tail pressure measurements were measured. At the end of experimental protocol, pulse wave velocity (PWV) was performed to analyze arterial stiffness. After measurement of direct arterial pressure (AP), autonomic balance and barroreflex analysis, aorta artery was removed for proteomic analysis and muscle tissues (soleus and left ventricle) for histological analyses. The sedentary hypertensive rats (SC) presented lower body weight (-26.51%) and lower SOL weight (-26%) compared to wistar rats. However, hemodynamic values of SBP, DBP and MAP were elevated (+ 69.61%, 62.33% and 63.53% respectively), as well as VOP (+ 49.35%) and sympathetic nerve activity for vessels (+ 64.33%) when compared to wistar. Spontaneous (non-pharmacological) barroreflex analysis of SC had values of reflex bradycardia (GAIN UP, -43.70%), as well as the sum of reduced reflex bradycardia and reflex tachycardia (GAIN ALL, -42.47%), when compared to wistar. The histological analysis of collagen density was increased (+ 136.80%) in SC rats, whereas C: F (+ 24.34%) was higher in wistar. PWV was higher and treatment with perindopril and / or T were able to reduce it in SHR (-36%, -21% and -46%, for SP, TF and TP, respectively), compared with SC. Media wall AST values were also reduced in the SP (-59%), TC (-55%) and TP (-44%) groups, compared with SC. In addition, LV collagen density was reduced after perindopril (-53%), T (-46%) and its association (-52%). Only trained groups presented higher values of capillary-to-fiber ratio (64% and 37%, for TC and TP respectively). Sympathetic nervous activity to the vessels was also reduced only after T. Proteomic analysis suggested that some proteins that were up regulated after perindopril, were contra balanced by T, through different pathways. Results of this study suggest that reduction of arterial stiffness induced by T maybe associated with renin angiontensin system, since reduction were similar to those after perindopril treatment. Besides functional responses were similar, proteomic results suggest that both strategies act through different protein pathway. Improvements of arterial stiffness may be also associated with local and neural skeletal muscle microcirculation alterationsand both treatments did not determine synergic responses.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-07-17T13:18:22Z
dc.date.available.fl_str_mv 2019-07-17T13:18:22Z
dc.date.issued.fl_str_mv 2019-03-27
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.citation.fl_str_mv MIOTTO, Danyelle Siqueira. Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos. 2019. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11513.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/11513
identifier_str_mv MIOTTO, Danyelle Siqueira. Os efeitos do treinamento físico, associado ao perindopril, na rigidez arterial de ratos espontaneamente hipertensos. 2019. Dissertação (Mestrado em Ciências Fisiológicas) – Universidade Federal de São Carlos, São Carlos, 2019. Disponível em: https://repositorio.ufscar.br/handle/ufscar/11513.
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