Efeitos da endotoxemia sobre o sistema Renina-Angiotensina renal de ratos Wistar
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Data
2013-09-25
Autores
Rosa, Rodolfo Mattar [UNIFESP]
Orientadores
Casarini, Dulce Elena [UNIFESP]
Tipo
Dissertação de mestrado
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Resumo
A sepse é um grande problema de saúde pública mundial, provocando a morte de cerca de 215 mil pessoas por ano com custos que chegam aos 17 bilhões de dólares. Essa doença é definida como uma resposta inflamatória sistêmica e descontrolada frente a uma infecção, sendo que um dos principais órgãos acometidos por ela é o rim, em especial quando ocorre infecção por bactérias Gram-negativas. Tendo em vista as alterações renais e cardiovasculares provocadas pela sepse, o objetivo do presente estudo foi verificar a modulação de alguns componentes do SRA em rim de animais tratados com lipopolissacarídeo de E. coli (LPS), um modelo de IRA decorrente da sepse.
Inicialmente, ratos Wistar receberam injeção de 4 mg/kg de LPS e foram eutanasiados 3 dias após o tratamento. Os animais endotoxêmicos mostraram redução do peso corporal e da pressão arterial. Os níveis plasmáticos de citocinas pró-inflamatórias não se encontrou alterado três dias após o tratamento. Contudo os valores de NO plasmático e iNOS renal também mostram-se reduzidos nos animais tratados com LPS. Isso indica que, em nosso modelo, 3 dias após a injeção de toxina, o NO não é mais o principal responsável pela manutenção da hipotensão e outras vias de vasodilatação podem estar mais ativadas. O ritmo de filtração glomerular não se alterou, o que foi evidenciado pela manutenção dos valores da depuração de creatinina entre os grupos. Contudo, a vasoconstrição renal parece estar instalada pelo tratamento com LPS, pois foram observados altos níveis de Ang II no rim desses animais. Além disso, esse peptídeo também pode estar associado à progressão da resposta inflamatória podendo desencadear dano tecidual. A ECA, principal produtora de Ang II, apresentou expressão e atividade diminuídas, indicando que vias alternativas da produção desse hormônio podem estar ativadas. Além disso, a renina também apresentou redução de atividade no rim endotoxêmico, indicando uma tentativa de controle de atividade do SRA. Dessa forma, o tratamento prolongado com LPS pareceu ativar vias compensatórias visando uma tentativa de volta à homeostase e de minimização dos danos provocados pela endotoxemia.
Sepsis is a major public health issue worldwide which causes around 215,000 deaths per year, and the costs of treatment may reach 17 billion dollars. This disease is defined as an uncontrolled systemic inflammatory response against an infection, and one of the major organs damaged by sepsis is the kidney, especially when the infection occurs by Gram-negative bacteria. Given the cardiovascular and renal changes provoked by sepsis, the aim of the present study was to investigate the modulation of some RAS components in the kidney of animals injected with E. coli lipopolysaccharide (LPS), a model of acute renal failure due to sepsis. Firstly, Wistar rats were injected intraperitoneally with LPS 4 mg/kg and were euthanized 3 days after treatment. Endotoxemic rats showed reduction in both body weight and blood pressure. The levels of plasmatic proinflammatory cytokines were not altered by LPS administration three days after treatment. However, the values of plasmatic NO and renal iNOS were decreased by endotoxemia. These data indicate that, in our animal model, three days after toxin injection, NO is no longer the main responsible for the hypotension and other factors may be more important for the maintenance of vasodilatation. The glomerular filtration rate did not change, which was evidenced by the maintenance in the creatinine clearance among the groups. However, renal vasoconstriction seems to be settled by LPS treatment, since high levels of Ang II were found in the kidney from endotoxemic rats. Moreover, this peptide can also be associated with the progression of the inflammatory response and it may be a possible cause of tissue damage. ACE, the main producer of renal Ang II, presented decreased expression and activity in the kidney, which indicates that alternative pathways for Ang II production are activated. Furthermore, renin also showed reduced activity in the endotoxic kidney, indicating an attempt in controlling RAS activity. In summary, prolonged treatment with LPS appears to activate compensatory pathways as targeting an attempt to return to homeostasis and to reduce the damage triggered by exdotoxemia.
Sepsis is a major public health issue worldwide which causes around 215,000 deaths per year, and the costs of treatment may reach 17 billion dollars. This disease is defined as an uncontrolled systemic inflammatory response against an infection, and one of the major organs damaged by sepsis is the kidney, especially when the infection occurs by Gram-negative bacteria. Given the cardiovascular and renal changes provoked by sepsis, the aim of the present study was to investigate the modulation of some RAS components in the kidney of animals injected with E. coli lipopolysaccharide (LPS), a model of acute renal failure due to sepsis. Firstly, Wistar rats were injected intraperitoneally with LPS 4 mg/kg and were euthanized 3 days after treatment. Endotoxemic rats showed reduction in both body weight and blood pressure. The levels of plasmatic proinflammatory cytokines were not altered by LPS administration three days after treatment. However, the values of plasmatic NO and renal iNOS were decreased by endotoxemia. These data indicate that, in our animal model, three days after toxin injection, NO is no longer the main responsible for the hypotension and other factors may be more important for the maintenance of vasodilatation. The glomerular filtration rate did not change, which was evidenced by the maintenance in the creatinine clearance among the groups. However, renal vasoconstriction seems to be settled by LPS treatment, since high levels of Ang II were found in the kidney from endotoxemic rats. Moreover, this peptide can also be associated with the progression of the inflammatory response and it may be a possible cause of tissue damage. ACE, the main producer of renal Ang II, presented decreased expression and activity in the kidney, which indicates that alternative pathways for Ang II production are activated. Furthermore, renin also showed reduced activity in the endotoxic kidney, indicating an attempt in controlling RAS activity. In summary, prolonged treatment with LPS appears to activate compensatory pathways as targeting an attempt to return to homeostasis and to reduce the damage triggered by exdotoxemia.
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Citação
ROSA, Rodolfo Mattar. Efeitos da endotoxemia sobre o sistema Renina-Angiotensina renal de ratos Wistar. São Paulo, 2013. 90 f. Dissertação (Mestrado em Medicina Translacional) – Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2013.