Efeitos do Exercício Físico Associado à N Acetilcisteína na Remodelação Cardíaca de Ratos Espontaneamente Hipertensos : Exercício e N-acetilcisteína na remodelação cardíaca
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2019-12-20
Autores
Junqueira, Adriana
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Universidade Estadual Paulista (Unesp)
Resumo
A hipertensão arterial está associada à alta morbidade e mortalidade pelas alterações estruturais e funcionais de órgãos alvo e às alterações metabólicas, com elevado risco de eventos cardiovasculares. A sobrecarga de pressão e o estresse oxidativo têm papel importante na remodelação cardíaca. A hipertensão arterial é um fator de risco modificável para as doenças cardiovasculares, onde os fármacos e o exercício físico regular são capazes de reduzir os níveis pressóricos de indivíduos hipertensos. Objetivo: Investigar os efeitos do exercício físico resistido combinado ao aeróbico associado à N-acetilcisteína na remodelação cardíaca em ratos espontaneamente hipertensos (SHR). Métodos: Os SHR foram divididos nos grupos sedentário (CTL, n=12), submetido ao exercício combinado (EXE, n=13), sedentário submetido à N-acetilcisteína (NAC, n=13), e ratos submetidos ao exercício combinado e à N-acetilcisteína (EXENAC, n=14). Os ratos dos grupos exercício combinado foram treinados três vezes por semana, durante dois meses, em esteira e escada. Os ratos suplementados receberam NAC durante dois meses, na ração. Testes de capacidade física aeróbica e resistido, avaliação da pressão arterial sistólica e o ecocardiograma foram realizados antes e após os protocolos de tratamento. As seguintes análises foram realizadas: morfometria, histomorfometria, estresse oxidativo, expressão gênica do complexo enzimático NADPH oxidase por RT-PCR real time e expressão de proteínas oxidadas por Western blot. Análise estatística: Para a análise entre os grupos foram realizadas a ANOVA para esquema de dois fatores, complementada com o teste de comparações múltiplas de Bonferroni (distribuição normal) ou o teste de Kruskal-Wallis complementado com o teste de comparações múltiplas de Dunn (distribuição não normal). Para o estudo de variação de medidas entre momentos inicial e final, foi utilizada a ANOVA de duas vias complementada com teste de Student-Newman-Keuls. Nível de significância de 5%. Resultados: Os ratos dos grupos submetidos aos protocolos de exercícios físico combinado apresentaram maior capacidade física aeróbica e de carga máxima que os animais controle após o período de treinamento. A variação (aumento) do diâmetro diastólico do ventrículo esquerdo (VE) indexado pelo peso corporal foi maior nos grupos EXE e NAC vs. CTL, e no grupo EXENAC a variação desse índice foi menor que nos grupos EXE e NAC. Ficou evidenciado que o exercício físico e a NAC, isoladamente, melhorou a função diastólica do VE de acordo com as variáveis E’ média, E/E’ média e A’ média. A função sistólica (VEPP) foi melhor no grupo EXENAC vs. EXE. A NAC teve ação importante na redução da peroxidação lipídica e, quando esteve associada ao exercício combinado, seu efeito foi ainda mais evidente. A catalase foi maior no grupo EXE (vs CTL) que diminuiu quando se associou a NAC. Em relação ao complexo enzimático da NADPH oxidase, observou-se aumento na expressão da p22 phox e da Nox2 no grupo EXE em comparação ao grupo CTL, sugerindo ativação da via sinalizadora do processo de remodelação cardíaca. A melhora de alguns parâmetros estruturais e funcionais cardíacas observada no grupo EXENAC pode estar associada à redução da expressão da p-JNK e da p-IkB e atenuação do marcador da peroxidação lipídica. Conclusão: O exercício físico aeróbico combinado ao resistido associado à N-acetilcisteína em ratos espontaneamente hipertensos atenua a remodelação cardíaca, que está associada a diminuição do marcador de estresse oxidativo e da expressão proteica da p-JNK e p-IkB.
Arterial hypertension is associated with high morbidity and mortality due to structural and functional alterations of target organs and metabolic alterations, with a high risk of cardiovascular events. Pressure overload and oxidative stress play an important role on cardiac remodeling. Arterial hypertension is a modifiable risk factor for cardiovascular disease, and medicines and regular exercise reduce blood pressure in hypertensive individuals. Objective: To investigate the effects of resistance exercise combined with aerobic exercise associated with N-acetylcysteine on cardiac remodeling in spontaneously hypertensive rats (SHR). Methods: SHR were divided into sedentary (CTL, n=12), combined exercise (EXE, n=13), Nacetylcysteine sedentary (NAC, n=13), and rats submitted to combined exercise and N-acetylcysteine (EXENAC, n=14). The rats of the combined exercise groups were trained three times a week for two months on a treadmill and ladder. Supplemented rats received NAC for two months in their rat chow. Aerobic and resistance physical capacity tests, systolic blood pressure measurements, and echocardiography were performed before and after treatment protocols. The following analysis were performed: morphometry, histomorphometry, oxidative stress, gene expression of NADPH oxidase enzyme complex by real time RT-PCR and Western blot oxidized protein expression. Statistical analysis: Comparison between groups were performed by two-way ANOVA, complemented with Bonferroni test (normal distribution), or Kruskal-Wallis complemented with Dunn test (non-normal distribution). The two-way ANOVA complemented with Student-Newman-Keuls test was used to compare initial and final data. The results were discussed at a significance level of 5%. Results: The rats of groups submitted to combined exercise protocols presented higher aerobic capacity and maximum load than the control animals. The variation (increase) in left ventricular (LV) diastolic diameter indexed by body weight was greater in EXE and NAC groups vs. CTL. In EXENAC group the increase of this index was smaller than in EXE and NAC groups. It was observed that physical exercise or NAC alone improves LV diastolic function according to the parameters E' average, E/E' average, and A' average. Systolic function (posterior wall shortening velocity index) was better in EXENAC vs. EXE. NAC reduced lipid peroxidation and when associated with combined exercise, its effect was even more evident. Catalase was higher in EXE group (vs. CTL) and decreased when associated with NAC. Regarding to NADPH oxidase enzymatic complex, it was observed increase of p22 phox and Nox2 Abstract 6 expression in EXE group compared to CTL, suggesting activation of cardiac remodeling signaling pathway. Improvement of some structural and functional parameters observed in EXENAC group may be associated with reduced expression of p-JNK and p-IkB and attenuation of lipid peroxidation. Conclusion: Combined aerobic and resistance exercise, associated with N-acetylcysteine, in spontaneously hypertensive rats attenuates cardiac remodeling, which is associated with reduction of oxidative stress and p-JNK and p-IkB protein expression.
Arterial hypertension is associated with high morbidity and mortality due to structural and functional alterations of target organs and metabolic alterations, with a high risk of cardiovascular events. Pressure overload and oxidative stress play an important role on cardiac remodeling. Arterial hypertension is a modifiable risk factor for cardiovascular disease, and medicines and regular exercise reduce blood pressure in hypertensive individuals. Objective: To investigate the effects of resistance exercise combined with aerobic exercise associated with N-acetylcysteine on cardiac remodeling in spontaneously hypertensive rats (SHR). Methods: SHR were divided into sedentary (CTL, n=12), combined exercise (EXE, n=13), Nacetylcysteine sedentary (NAC, n=13), and rats submitted to combined exercise and N-acetylcysteine (EXENAC, n=14). The rats of the combined exercise groups were trained three times a week for two months on a treadmill and ladder. Supplemented rats received NAC for two months in their rat chow. Aerobic and resistance physical capacity tests, systolic blood pressure measurements, and echocardiography were performed before and after treatment protocols. The following analysis were performed: morphometry, histomorphometry, oxidative stress, gene expression of NADPH oxidase enzyme complex by real time RT-PCR and Western blot oxidized protein expression. Statistical analysis: Comparison between groups were performed by two-way ANOVA, complemented with Bonferroni test (normal distribution), or Kruskal-Wallis complemented with Dunn test (non-normal distribution). The two-way ANOVA complemented with Student-Newman-Keuls test was used to compare initial and final data. The results were discussed at a significance level of 5%. Results: The rats of groups submitted to combined exercise protocols presented higher aerobic capacity and maximum load than the control animals. The variation (increase) in left ventricular (LV) diastolic diameter indexed by body weight was greater in EXE and NAC groups vs. CTL. In EXENAC group the increase of this index was smaller than in EXE and NAC groups. It was observed that physical exercise or NAC alone improves LV diastolic function according to the parameters E' average, E/E' average, and A' average. Systolic function (posterior wall shortening velocity index) was better in EXENAC vs. EXE. NAC reduced lipid peroxidation and when associated with combined exercise, its effect was even more evident. Catalase was higher in EXE group (vs. CTL) and decreased when associated with NAC. Regarding to NADPH oxidase enzymatic complex, it was observed increase of p22 phox and Nox2 Abstract 6 expression in EXE group compared to CTL, suggesting activation of cardiac remodeling signaling pathway. Improvement of some structural and functional parameters observed in EXENAC group may be associated with reduced expression of p-JNK and p-IkB and attenuation of lipid peroxidation. Conclusion: Combined aerobic and resistance exercise, associated with N-acetylcysteine, in spontaneously hypertensive rats attenuates cardiac remodeling, which is associated with reduction of oxidative stress and p-JNK and p-IkB protein expression.
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Palavras-chave
Exercícios físicos, Hipertensão, Estresse oxidativo, N-acetilcisteína, Proteínas quinases ativadas por mitógeno, Fator nuclear kappa-B, Remodelação ventricular