Influência do Nebivolol sobre o estresse oxidativo em pacientes hipertensos
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Data
2017-07-21
Autores
Barroso, Helena Cordeiro [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O Nebivolol (Neb) é um antagonista dos receptores β1-Adrenérgicos (β1-RA) de terceira geração que causa vasodilatação efeito mediado pelo óxido nítrico e redução do estresse oxidativo (EO) em modelos pré-clínicos e estudos clínicos de Hipertensão Arterial Sistêmica (HAS). Este estudo avaliou os níveis de biomarcadores de estresse oxidativo e atividade de sistemas antioxidantes enzimáticos e não-enzimáticos na saliva de pacientes hipertensos antes e após o tratamento com doses terapêuticas anti-hipertensivas de Neb. Vinte e quatro pacientes hipertensos foram tratados com 5 mg/dia de Neb por oito semanas consecutivas. Amostras de saliva não estimulada foram coletadas de pacientes com idade entre 25 a 70 anos para análise da capacidade antioxidante total (CAT), a qual foi medida pelo Método FRAP (Ferric Reducing Antioxidant Power), a atividade enzimática da superóxido dismutase (SOD) e quantificação do ácido úrico (AU) antes (NT, grupo não tratado) e após tratamento (T, grupo tratado) com Neb. Adicionalmente, parâmetros clínicos, bioquímicos e eletrocardiográficos foram avaliados em ambos os grupos. Os grupos foram comparados pelo teste t de Student, pareado (p<0,05). Neb não alterou os valores de CAT (NT:1,697 ± 0,433 versus T: 1,674 ± 0,092 mmol/L, p=0,8454), ou a atividade da SOD (EA- NT: 66,56 ± 4,977 versus T: 60,66 ± 6,376 UE/mL, p=0,4886) na saliva. No entanto, o tratamento com Neb aumentou a concentração do AU em pacientes tratados (NT: 24,64 ± 1,686 versus T: 35,56 ± 2,014 mg/mL, p=0,0002). Os parâmetros clínicos, bioquímicos e eletrocardiográficos foram positivamente alterados com o tratamento com Neb. Nosso estudo demonstrou que o tratamento com Neb aumentou o AU na saliva de pacientes hipertensos em contexto de prática clínica real, aumentando a atividade do sistema antioxidante não-enzimático na saliva de pacientes que foram tratados com Neb. Nossos dados sugerem que o Neb pode estender seu potencial terapêutico, elevando a proteção cardiovascular contra o estresse oxidativo em adição ao seu efeito anti-hipertensivo.
Nebivolol (Neb) is third-generation selective β1-adrenergic receptor antagonist which causes vasodilation (by nitric oxide release) and has been shown to reduce oxidative stress (OS) in pre-clinical models and clinical studies. This study aimed to evaluate the OS levels and the enzymatic and non-enzymatic antioxidant systems in saliva of patients with ESH before and after anti-hypertensive therapeutic doses of Neb. Twenty-four essential hypertensive patients were treated with 5 mg Neb once daily for a total of 8 weeks. Unstimulated saliva samples were collected from 25 to 70 years-old patients for evaluation of total antioxidant capacity (TAC), which were measured by the ferric reducing antioxidant power (FRAP) assay, as well as to assess the activity of enzymatic (superoxide dismutase, SOD) and non-enzymatic (uric acid, UA) antioxidant systems, respectively before (C, control group) and after treatment (T, treated group) with Neb. Additionally, clinical, biochemical and electrocardiographic parameters were evaluated in both groups. Data were analyzed by paired Student’s t-test (p < 0.05). Neb did not alter TAC values (UT: 1,697 ± 0,433 versus T: 1,674 ± 0,092 mmol/L, p=0,8454), or SOD activity (EA-UT: 66,56 ± 4,977 versus T: 60,66 ± 6,376 UE/mL, p=0,4886) in saliva. However, Neb treatment increased salivary UA activity in treated patients (UT: 24,64 ± 1,686 versus T: 35,56 ± 2,014 mg/mL, p=0,0002). Clinical, electrocardiographic and biochemical parameters were positively changed with Neb treatment. Our study showed that Neb increased UA, an OS biomarker, in saliva of hypertensive patients in a context of real clinical practice. Therefore this compound could extend its therapeutic potential, providing cardiovascular protection in addition to its β1-antagonist effect.
Nebivolol (Neb) is third-generation selective β1-adrenergic receptor antagonist which causes vasodilation (by nitric oxide release) and has been shown to reduce oxidative stress (OS) in pre-clinical models and clinical studies. This study aimed to evaluate the OS levels and the enzymatic and non-enzymatic antioxidant systems in saliva of patients with ESH before and after anti-hypertensive therapeutic doses of Neb. Twenty-four essential hypertensive patients were treated with 5 mg Neb once daily for a total of 8 weeks. Unstimulated saliva samples were collected from 25 to 70 years-old patients for evaluation of total antioxidant capacity (TAC), which were measured by the ferric reducing antioxidant power (FRAP) assay, as well as to assess the activity of enzymatic (superoxide dismutase, SOD) and non-enzymatic (uric acid, UA) antioxidant systems, respectively before (C, control group) and after treatment (T, treated group) with Neb. Additionally, clinical, biochemical and electrocardiographic parameters were evaluated in both groups. Data were analyzed by paired Student’s t-test (p < 0.05). Neb did not alter TAC values (UT: 1,697 ± 0,433 versus T: 1,674 ± 0,092 mmol/L, p=0,8454), or SOD activity (EA-UT: 66,56 ± 4,977 versus T: 60,66 ± 6,376 UE/mL, p=0,4886) in saliva. However, Neb treatment increased salivary UA activity in treated patients (UT: 24,64 ± 1,686 versus T: 35,56 ± 2,014 mg/mL, p=0,0002). Clinical, electrocardiographic and biochemical parameters were positively changed with Neb treatment. Our study showed that Neb increased UA, an OS biomarker, in saliva of hypertensive patients in a context of real clinical practice. Therefore this compound could extend its therapeutic potential, providing cardiovascular protection in addition to its β1-antagonist effect.
Descrição
Palavras-chave
Nebivolol, Estresse oxidativo, Hipertensão, Humanos, Oxidative stress, Hypertension, Human beings