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Effects of TNF-alfa inhibition on vascular hypertrophy associated with renovascular hypertension

Grant number: 16/17484-9
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): February 01, 2017
Effective date (End): January 31, 2018
Field of knowledge:Biological Sciences - Morphology - Histology
Principal Investigator:Elen Rizzi Sanchez
Grantee:Victória Thomazelli Garcia
Host Institution: Universidade de Ribeirão Preto (UNAERP). Campus Ribeirão Preto. Ribeirão Preto , SP, Brazil


The activation of renin-angiotensin system (RAS) is involved in the complications associated with hypertension as vascular hypertrophy and endothelial dysfunction. The activation of RAS and consequently, increase of Angiotensin II (AngII) occurs in experimental model of hypertension 2-kidney 1-clip (2K1C) . In this sense, 2K1C rats is a good experimental model to evaluate the effects of AngII and RAS. Evidences has suggested that the cytokine TNF-± is required for AngII-induced hypertrophy and fibrosis cardiac. However, no study evaluated the interaction between TNF-± and AngII in the vascular hypertrophy. AngII and TNF-± may increase the formation of reactive oxygen species (ROS). In the hypertension, ROS is the main factor responsible for matrix metalloproteinases (MMPs) activation. These proteases degrade the extracellular matrix promoting cardiovascular remodelling. Thus, the hypothesis of the present project is that TNF-± inhibition revert the vascular morphological changes in animals 2K1C and decrease the ROS formation and gelatinase activity, which is increased in these hypertensive animals. To evaluate this hypothesis will be used animals sham and 2K1C treated or not with inhibitor of TNF-± (Pentoxifylline). The animals will be operated and after two weeks of surgery will be randomized in four experimental groups: (I) Sham, (II) 2K1C, (III) Sham+Pentoxifylline and (IV) 2K1C+Pentoxifylline. The blood pressure of the animals will be measured weekly by tail plethysmography. The vascular hypertrophy will be evaluated in aorta cuts stained with hematoxylin and eosin. In these cuts, will be evaluated the cross sectional area (CSA), number of the cells and the reason between media per lumen (M/L). The increased ROS will be evaluated by DHE fluorescence in cuts of aorta. The activity of MMPs will be observed by in situ zymography. (AU)

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