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Effects of Vitamin D in the arterial hypertension and in the ischemic renal injury induced by chronic stenosis of renal artery induced by 2kidneys-1 clip model

Grant number: 12/11607-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2012
Effective date (End): August 31, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Mirian Aparecida Boim
Grantee:Daniele Berruezo Lucio Silva
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The renovascular hypertension (HARV) is caused by a partial or complete obstruction of the renal artery. The experimental model of HARV most widely used was developed by Goldblatt in 1934, which consists in placing a silver clip on the left renal artery, also known as 2 kidney - 1 clip (2K-1C) model. The objective of this model is to reduce blood flow in 50% and activate the Renin Angiotensin-Aldosterone system (RAAS), resulting in a raise of the systolic blood pressure (SBP). Control of this condition is still critical, so we set out to test the hypothesis that treatment with vitamin D could be useful in minimizing the HARV based on the following criteria: 1 - The HARV is dependent on activation of the RAAS, 2 - Vit D is capable of reducing the activity of the renin gene 3 - Vit D has renoprotective effects with anti-inflammatory action. Male Wistar adult rats will be subject to partial clamping of the left renal artery. After the 3rd. week, when the pressure levels are significantly high, vitamin D will be administered at a dosage 0.5 ug/kg (ip) until the sixth week. The PAS will be monitored weekly using the plethysmography method. 24 hours urine and blood samples samples will be collected before and after treatment for biochemical tests. The expression of renin and other components of the RAS by western blotting and real-time PCR will be evaluated in the cortex and medulla of the clipped kidney The systemic activity of RAS will be assessed by plasma renin activity. Hematoxylin and eosin staining (HE) will be used to analyze the renal morphology. Renal function will be estimated by creatinine clearance, proteinuria and dosage of plasma and urinary sodium and potassium.