Acute hemorrhage in rats anesthetized with sevoflurane and under the effect of losartan. Mechanisms of renal cell death by hypoxia: intrinsic and extrinsic pathway of apoptosis

• Grant number: 11/06167-9
• Support type: Scholarships in Brazil - Post-Doctorate
• Effective date (Start): December 01, 2011
• Effective date (End): November 30, 2014
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal researcher: Yara Marcondes Machado Castiglia
• Grantee: Marcela Marcondes Pinto Rodrigues
• Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Hemorrhagic shock, the focus of studies in experimental models, is the change that must becontrolled in patients who undergo surgical procedures because it results in hypotension andorgan failure, especially kidneys. The advance of renal injury is closely associated to levels ofangiotensin II due to its hemodynamic and non-hemodynamic activity. The use of angiotensinAT1 receptor blockers promotes organ perfusion under conditions of severe hemorrhage,however, as those blockers determine hypotension of difficult control it may interfere with renalperfusion pressure. The purpose of the present study is study the mechanism of renal injury inrats submitted to acute hemorrhage previously treated with the AT1 receptor blocker, losartan,and assessment of apoptosis, proliferation and production of reactive oxygen species andexpression of IL-6 and TNF-±. Wistar rats anesthetized with sevoflurane and divided into fourgroups: placebo without hemorrhage; losartan without hemorrhage; placebo with hemorrhage,losartan with hemorrhage. The kidney function will be studied with urineless method. All animalswill be submitted to bilateral nephrectomy for analysis of gene expression (qRT-PCR), proteinexpression (immunohistochemistry and Western blotting) and morphology analysis. The resultswill be discussed at a significance level of 5%.Key-words: Losartan, IL-6, TNF-±, NADPH oxidase, proliferation, apoptosis.