Disfunção renal induzida por modelo polimicrobiano de Sepse: avaliação de componentes do sistema renina-angiotensina

• Ano de defesa: 2011
• Autor(a) principal: Lucio Ricardo Leite Diniz
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Sepse; sistema renina angiotensina; disfunção renal; Rins Fisiologia; Sistema renina-angiotensina Fisiologia; Insuficiencia renal aguda; Septicemia; Fisiologia; Rins Doenças
• Link de acesso: http://hdl.handle.net/1843/ICBD-8LPKB4

Sepsis, a systemic inflammatory response syndrome caused by infection, is the most predisposing factor for development of acute kidney injury (AKI). An intensive inflammatory response associated with circulatory disturbances characterized by hypotension, vascular damage and hyporesponsiveness to vasoconstrictors are important factors involved in the sepsis-induced AKI. The control of hemodynamic parameters, mainly blood pressure regulation, and the development of inflammatory cascade are some of the roles attributed to renin-angiotensin system (RAS). It has been reported two different axis in RAS. The first one, denominated vasoconstrictor axis, is formed by ACE - Ang II AT1 receptor and its blocked shows renoprotector effect in renal disease promoted by hypertension, ischemia and diabetis. The second axis is composed by ACE2 - Ang - (1-7) - Mas receptor axis and produces a counter-regulatory activity, in majority of tissues, inducing opposite effects by which induced by vasoconstrictor axis. Therefore, the involvement of the counter-regulatory arm of RAS on sepsis-induced renal dysfunction and kidney inflammatory responses was evaluated 6, 12 and 24 h after Cecal Ligation and Puncture (CLP) surgery. The effects of exogenous Angiotensin-(1-7) were also investigated. Sepsis produces an increase in the components of the SRA two axis, as evidenced by increased renal expression of mRNA encoding ACE and ACE 2 as well as by increase of renal content of Ang II and Ang-(1-7). The ratios of renal expression ECA/ECA2 and renal content of Ang II / Ang - (1-7) were similar in the sham and CLP groups. A downregulation of the receptor in CLP animals, evidenced by a staining reduced intensity the cortex Mas receptor was also observed. Treatment with Ang-(1-7) reduced the renal concentrations of TNF-, IL-6, infiltration of neutrophils, reduced urinary volume, increased clearance creatinine and decreased microalbuminuria when compared to untreated CLP animals. We have showed that renal protective effects produced by a single Ang-(1-7) administration still remained 7 days after treatment. In summary, we showed that the SRA counter-regulatory axis is activated in the sepsis-induced AKI and that the effects of administration of Ang-(1-7) exhibited anti-inflammatory and renal protective