Avaliação do papel da via do triptofano e do exercício físico aeróbio sobre o efeito hipotensor do alpiste (phalaris canariensis) em ratos espontaneamente hipertensos
Data
2015-07-31
Autores
Passos, Clévia dos Santos 
Orientadores
Boim, Mirian Aparecida Boim
Tipo
Tese de doutorado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
Foi demonstrado anteriormente que o Phalaris canariensis (Pc), conhecido popularmente por alpiste, foi capaz de reduzir a PA em ratos espontaneamente hipertensos (SHR), o que foi atribuído ao triptofano, que pode ser metabolizado pela rota da quinurenina, um agente vasodilatador, através da enzima indoleamina 2,3 dioxigenase (IDO). Por outro lado, o exercício físico (EF) tem sido um grande aliado no tratamento de doenças cardiovasculares. Considerando essas duas estratégias, o objetivo deste estudo foi avaliar se a associação do exercício físico potencializa o efeito anti-hipertensivo do extrato aquoso do Phalaris canariensis (EAPc) em SHR e quais os mecanismos envolvidos. Para tanto, utilizamos dois protocolos experimentais, agudo e crônico, ambos utilizando SHR adultos (250-260g). No tratamento agudo, os animais foram separados nos grupos, controle (H2O); tratados com EAPc (400 mg/kg/dia) na presença e ausência do inibidor da IDO (1MT, 50mg/kg); tratados com triptofano (100mg/kg). No estudo crônico, a associação do EF e EAPc foi avaliada nos seguintes grupos: controle sedentário (H2O Sed); tratado com EAPc (400 mg/kg, v.o.) (EAPc-Sed,); controle exercício (H2O-Ex); tratado com EAPc e exercício (EAPc-Ex). O protocolo do treinamento aeróbio foi em esteira ergométrica por oito semanas. A reatividade vascular foi avaliada in vitro, através de resposta de anéis de aorta a agentes vasoativos nos grupos controle (H2O) e SHR tratado com EAPc durante quatro semanas. Resultados: A administração aguda do EAPc induziu redução em 10% na PAM semelhante à produzida pelo triptofano (9%). Esse efeito foi abolido pelo inibidor da enzima IDO. Houve maior relaxamento vascular dependente de endotélio em resposta à acetilcolina em anéis de aorta provenientes de SHR tratados. O EAPc e o EF isoladamente tiveram efeitos benéficos sobre vários parâmetros metabólicos, nos marcadores de inflamação no rim como a expressão de IL-1 e sobre o sistema cardiovascular com redução semelhante na PAM. A associação das duas estratégias resultou em potencialização da maioria desses efeitos benéficos. Conclusão: O metabolismo do triptofano via IDO pode ser um dos mediadores do efeito hipotensor do EAPc. O tratamento com EAPc favoreceu melhora endotelial. Tanto o EAPc quanto o TF produziram efeitos benéficos sobre o metabolismo da glicose, inflamação e sistema cardiovascular. Esses efeitos foram potencializados com a associação das duas estratégias.
It was previously demonstrated that Phalaris canariensis (Pc), known as birdseed, was able to reduce blood pressure in spontaneously hypertensive rats (SHR), which was assigned to tryptophan, which can be metabolized by through kynurenine pathway, vasodilator agent, through the enzyme indoleamine 2,3-dioxygenase (IDO). On the other hand, the physical exercise (PE) has been a great ally in the treatment of cardiovascular diseases. The aim of this study was to evaluate the association of PE with the aqueous extract of Phalaris canariensis (AEPc) in SHR. For that, it was employed 2 protocols: acute and chronic. Adult male SHR were used (250-260g). In the acute treatment, the animals were divided into groups: control (H2O); treated with AEPc in the presence and absence of the IDO inhibitor; treated with tryptophan. The chronic association of PE and the AEPc was evaluated in the following groups: untreated sedentary control (H2O Sed); treated with AEPc (400 mg / kg, p.o.) (AEPc- Sed); control exercise (H2O Ex); treated with AEPc and exercise (AEPc-Ex). The aerobic training was performed on a treadmill during 8 weeks. Vascular reactivity was assessed in vitro, in SHR control (H2O) and treated with AEPc during 4 weeks. Results: The acute administration of AEPc induced reduction of 10% in MAP, similar to that produced by tryptophan (9%). This effect was abolished by the IDO inhibitor. Chronically, AEPc favored better endothelium-dependent vascular relaxation response to acetylcholine. The AEPc and PE alone had beneficial effects on the cardiovascular system, metabolic parameters and IL-1 expression in the kidney. The combination of the two strategies resulted in potentiation of most of these beneficial effects. Conclusion: The metabolism of tryptophan via IDO pathway can be one of the mediators of the hypotensive effect of AEPc. Chronically AEPc treatment improved endothelial mediated vasorelaxation. Both the AEPc as PE produced beneficial effects on glucose metabolism, inflammation and cardiovascular system. These effects were potentiated with the combination of both strategies.
It was previously demonstrated that Phalaris canariensis (Pc), known as birdseed, was able to reduce blood pressure in spontaneously hypertensive rats (SHR), which was assigned to tryptophan, which can be metabolized by through kynurenine pathway, vasodilator agent, through the enzyme indoleamine 2,3-dioxygenase (IDO). On the other hand, the physical exercise (PE) has been a great ally in the treatment of cardiovascular diseases. The aim of this study was to evaluate the association of PE with the aqueous extract of Phalaris canariensis (AEPc) in SHR. For that, it was employed 2 protocols: acute and chronic. Adult male SHR were used (250-260g). In the acute treatment, the animals were divided into groups: control (H2O); treated with AEPc in the presence and absence of the IDO inhibitor; treated with tryptophan. The chronic association of PE and the AEPc was evaluated in the following groups: untreated sedentary control (H2O Sed); treated with AEPc (400 mg / kg, p.o.) (AEPc- Sed); control exercise (H2O Ex); treated with AEPc and exercise (AEPc-Ex). The aerobic training was performed on a treadmill during 8 weeks. Vascular reactivity was assessed in vitro, in SHR control (H2O) and treated with AEPc during 4 weeks. Results: The acute administration of AEPc induced reduction of 10% in MAP, similar to that produced by tryptophan (9%). This effect was abolished by the IDO inhibitor. Chronically, AEPc favored better endothelium-dependent vascular relaxation response to acetylcholine. The AEPc and PE alone had beneficial effects on the cardiovascular system, metabolic parameters and IL-1 expression in the kidney. The combination of the two strategies resulted in potentiation of most of these beneficial effects. Conclusion: The metabolism of tryptophan via IDO pathway can be one of the mediators of the hypotensive effect of AEPc. Chronically AEPc treatment improved endothelial mediated vasorelaxation. Both the AEPc as PE produced beneficial effects on glucose metabolism, inflammation and cardiovascular system. These effects were potentiated with the combination of both strategies.
Descrição
Citação
PASSOS, Clevia dos Santos. Avaliação do papel da via do triptofano e do exercício físico aeróbio sobre o efeito hipotensor do alpiste (phalaris canariensis) em ratos espontaneamente hipertensos. 2015. 86 f. Tese (Doutorado em Nefrologia) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2015.