Impacto do tratamento farmacológico e do treinamento físico nas alterações renais associadas à hipertensão experimental: papel da modulação simpática vascular
Data
2021-12-16
Autores
Shecaira, Tânia Plens 
Orientadores
De Angelis, Kátia
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Objetivo: Investigar os efeitos do treinamento físico combinado (TFC) associado a terapias farmacológicas anti-hipertensivas em parâmetros morfofuncionais, inflamatórios e de estresse oxidativo renais, bem como na variabilidade da pressão arterial (VPA) em um modelo experimental de hipertensão arterial. Métodos: Foram utilizados 48 ratos machos SHR divididos em grupos (n=8/grupo) sedentários ou treinados: placebo (MSP e MTP), hidroclorotiazida 30 mg/kg/dia (MSH e MTH) e enalapril 3 mg/kg/dia (MSE e MTE). O TFC (aeróbico + resistido), 3 vezes por semana, foi realizado concomitante ao tratamento farmacológico por 8 semanas. Foi realizada avaliação da função renal por meio de coletas em gaiola metabólica por 24h, registro direto da PA, análise da VPA e análises histológicas, inflamatórias e de estresse oxidativo em tecido renal. Resultados: Os grupos treinados obtiveram melhora nos testes de capacidade física ao final do protocolo. O TFC isoladamente não alterou a PAS e a função renal, todavia, reduziu a razão média/lumen de artérias interlobulares (M/L) e a incidência de áreas com fibrose túbulo intersticial (26-50%) e a atividade da NADPH oxidase e aumentou a IL-10 e a atividade da SOD em tecido renal em relação ao grupo MSP. O grupo MSH apresentou redução da PAS e melhora de aspectos morfofuncionais renais, com aumento do clearance de creatinina e menor razão M/L e incidência de áreas com fibrose túbulo intersticial, sendo estas alterações acompanhadas de menor variância da PAS, modulação simpática vascular (MSH: 7,3±0,9 vs. MSH: 22,0±3,1 mmHg²), IL-6 e peróxido de hidrogênio e aumento da atividade da SOD renal. O grupo MTH apresentou diminuição da creatinina plasmática além dos benefícios observados no grupo MSH, com redução adicional na razão M/L e na fibrose túbulo intersticial em relação ao grupo MSH (faixa de lesão 51-100%: MTH: 2,5±0,1 vs. MSP: 27,5±0,1, MTP: 22,5±0,1 e MSH:15±0,0 %). O grupo MSE reduziu a PAS, a razão M/L, sendo estas alterações acompanhadas de diminuição da variância da PAS, IL-6 e peróxido de hidrogênio e aumento da atividade da SOD em tecido renal. Já o grupo MTE apresentou as alterações descritas no grupo MSE e, adicionalmente, teve redução da modulação simpática vascular (MTE: 10,6±1,7 vs. MSP: 22,0±3,1 mmHg²), aumento do clearance de creatinina e diminuição da fibrose túbulo intersticial (faixa de lesão 51-100%: MTE: 10,0±0,2 vs. MSP: 27,5±0,1, MTP: 22,5±0,1 e MSE: 22,5±0,1%), bem como potencializou a redução da razão M/L. Correlações positivas foram obtidas entre a modulação simpática vascular (BF) com a PAS, a razão M/L e a fibrose túbulo intersticial renal. Conclusões: A associação de medicamentos anti-hipertensivos, enalapril ou hidroclorotiazida, com o treinamento físico combinado em comparação aos efeitos do uso isolado dos medicamentos induziu redução da PAS em magnitude semelhante, todavia promoveu benefícios morfofuncionais renais adicionais (aumento do clearance de creatinina e redução da razão média/lumen das artérias interlobulares e da fibrose túbulo intersticial), os quais foram correlacionados com menor modulação simpática vascular.
Objective: To investigate the effects of combined exercise training (CET) associated with antihypertensive pharmacological therapies on renal morphofunctional, inflammatory and oxidative stress parameters, as well as on blood pressure variability (BPV) in an experimental model of arterial hypertension. Methods: Forty-eight male SHR rats were divided into groups (n=8/group): sedentary or trained: placebo (MSP and MTP), hydrochlorothiazide 30 mg/kg/day (MSH and MTH) and enalapril 3 mg/kg/day (MSE and MTE). CET (aerobic + resistance), 3 times a week, was performed concomitantly with pharmacological treatment for 8 weeks. We evaluated renal function using samples from a metabolic cage for 24 hours, direct blood pressure (BP) recording, BPV analysis and histological, inflammatory and oxidative stress parameters in renal tissue. Methods: Forty-eight male SHR rats were divided into groups (n=8/group) sedentary or trained: placebo (MSP and MTP), hydrochlorothiazide 30 mg/kg/day (MSH and MTH) and enalapril 3 mg/kg/day (MSE and MTE). CET (aerobic + resistance), 3 times a week, was performed concomitantly with pharmacological treatment for 8 weeks. Renal function was evaluated through collections in metabolic cage for 24 hours, direct recording of PA, analysis of VPA and histological, inflammatory and oxidative stress analyzes in renal tissue. Results: The trained groups improved in the physical capacity at the end of the protocol. CET alone did not change systolic BP (SBP) and renal function; however, it reduced the interlobular arteries mean/lumen ratio (M/L) and the incidence of areas with interstitial tubule fibrosis (26-50%) and the activity of NADPH oxidase and increased IL-10 and SOD activity in renal tissue compared to the MSP group. The MSH group showed reduced SBP and improved renal morphofunctional aspects, with increased creatinine clearance and lower M/L ratio and interstitial tubule fibrosis, these changes were accompanied by lower SBP variance, vascular sympathetic modulation (MSH: 7.3±0.9 vs. MSH: 22.0±3.1 mmHg²), IL-6 and hydrogen peroxide and increased SOD activity in renal tissue. The MTH group showed a decrease in plasma creatinine in addition to the benefits observed in the MSH group, with an additional reduction in the M/L ratio and in interstitial tubule fibrosis compared to the MSH group (lesion range 51-100%: MTH: 2.5±0.1 vs. MSP: 27.5± 0.1, MTP: 22.5±0.1 and MSH: 15±0.0%). The MSE group reduced the SBP, the M/L ratio, and these changes were accompanied by decreased variance in SBP, IL-6 and hydrogen peroxide and increased SOD activity in renal tissue. The MTE group presented the alterations described in the MSE group and, additionally, had a reduction in vascular sympathetic modulation (MTE: 10.6±1.7 vs. MSP: 22.0±3.1 mmHg²), increased creatinine clearance and decreased interstitial tubule fibrosis (lesion range 51-100%: MTE: 10.0±0.2 vs. MSP: 27.5±0.1, MTP: 22.5±0.1 and MSE: 22,5±0.1%), as well as potentiated the reduction of the M/L ratio. Positive correlations were obtained between vascular sympathetic modulation (BF) with SBP, M/L ratio and renal tubule interstitial fibrosis. Conclusions: The association of antihypertensive drugs, enalapril or hydrochlorothiazide, with CET compared to the effects of the isolated use of the drugs induced reduction in similar magnitude on SBP; however, it promoted additional renal morphofunctional benefits (increase in creatinine clearance and reduction in the ratio mean/lumen of interlobular arteries and in the tubule interstitial fibrosis), which were correlated with lower vascular sympathetic modulation.
Objective: To investigate the effects of combined exercise training (CET) associated with antihypertensive pharmacological therapies on renal morphofunctional, inflammatory and oxidative stress parameters, as well as on blood pressure variability (BPV) in an experimental model of arterial hypertension. Methods: Forty-eight male SHR rats were divided into groups (n=8/group): sedentary or trained: placebo (MSP and MTP), hydrochlorothiazide 30 mg/kg/day (MSH and MTH) and enalapril 3 mg/kg/day (MSE and MTE). CET (aerobic + resistance), 3 times a week, was performed concomitantly with pharmacological treatment for 8 weeks. We evaluated renal function using samples from a metabolic cage for 24 hours, direct blood pressure (BP) recording, BPV analysis and histological, inflammatory and oxidative stress parameters in renal tissue. Methods: Forty-eight male SHR rats were divided into groups (n=8/group) sedentary or trained: placebo (MSP and MTP), hydrochlorothiazide 30 mg/kg/day (MSH and MTH) and enalapril 3 mg/kg/day (MSE and MTE). CET (aerobic + resistance), 3 times a week, was performed concomitantly with pharmacological treatment for 8 weeks. Renal function was evaluated through collections in metabolic cage for 24 hours, direct recording of PA, analysis of VPA and histological, inflammatory and oxidative stress analyzes in renal tissue. Results: The trained groups improved in the physical capacity at the end of the protocol. CET alone did not change systolic BP (SBP) and renal function; however, it reduced the interlobular arteries mean/lumen ratio (M/L) and the incidence of areas with interstitial tubule fibrosis (26-50%) and the activity of NADPH oxidase and increased IL-10 and SOD activity in renal tissue compared to the MSP group. The MSH group showed reduced SBP and improved renal morphofunctional aspects, with increased creatinine clearance and lower M/L ratio and interstitial tubule fibrosis, these changes were accompanied by lower SBP variance, vascular sympathetic modulation (MSH: 7.3±0.9 vs. MSH: 22.0±3.1 mmHg²), IL-6 and hydrogen peroxide and increased SOD activity in renal tissue. The MTH group showed a decrease in plasma creatinine in addition to the benefits observed in the MSH group, with an additional reduction in the M/L ratio and in interstitial tubule fibrosis compared to the MSH group (lesion range 51-100%: MTH: 2.5±0.1 vs. MSP: 27.5± 0.1, MTP: 22.5±0.1 and MSH: 15±0.0%). The MSE group reduced the SBP, the M/L ratio, and these changes were accompanied by decreased variance in SBP, IL-6 and hydrogen peroxide and increased SOD activity in renal tissue. The MTE group presented the alterations described in the MSE group and, additionally, had a reduction in vascular sympathetic modulation (MTE: 10.6±1.7 vs. MSP: 22.0±3.1 mmHg²), increased creatinine clearance and decreased interstitial tubule fibrosis (lesion range 51-100%: MTE: 10.0±0.2 vs. MSP: 27.5±0.1, MTP: 22.5±0.1 and MSE: 22,5±0.1%), as well as potentiated the reduction of the M/L ratio. Positive correlations were obtained between vascular sympathetic modulation (BF) with SBP, M/L ratio and renal tubule interstitial fibrosis. Conclusions: The association of antihypertensive drugs, enalapril or hydrochlorothiazide, with CET compared to the effects of the isolated use of the drugs induced reduction in similar magnitude on SBP; however, it promoted additional renal morphofunctional benefits (increase in creatinine clearance and reduction in the ratio mean/lumen of interlobular arteries and in the tubule interstitial fibrosis), which were correlated with lower vascular sympathetic modulation.