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Mechanisms underlying the reduction of urinary albumin excretion induced by the pharmacological blockade of the renin-angiotensin system in renovascular hypertensive rats

Grant number: 13/00870-5
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2013
Effective date (End): September 30, 2014
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Adriana Castello Costa Girardi
Grantee:Karoline Ruivo Boaro
Home Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Epidemiological studies show that there is a positive correlation between urinary albumin excretion and the frequency of cardiovascular events and mortality in patients with hypertension. Increased urinary albumin excretion may be due to increased glomerular permeability and/or a decreased reabsorption of this macromolecule in the proximal tubule. In clinical practice, it has been observed that inhibitors of angiotensin converting enzyme as well as angiotensin II AT-1 receptor antagonists exhibit higher capacity to reduce albuminuria than other classes of antihypertensive drugs, suggesting that antagonists of the renin angiotensin system (RAS) promote additional renoprotective effects that are independent of blood pressure reduction. In this project we propose to elucidate the molecular mechanisms involved in the reduction of urinary albumin excretion induced by pharmacological blockade of the RAS in renovascular hypertensive rats. More specifically we will test the following hypothesis: (1) that the double blockade of the RAS exerts superior anti-albuminuric effects than the monotherapy with enalapril or losartan in rats with renovascular hypertension; (2) that rats with renovascular hypertension exhibit decreased expression of essential proteins that maintain the integrity of the glomerular filtration barrier and that the treatment with RAS blockers are able to restore the expression of these proteins; (3) that rats with renovascular hypertension exhibit decreased expression of essential proteins that mediate proximal tubular reabsorption of albumin and that the treatment with RAS blockers are able to restore the expression of these proteins; (4) that rats with renovascular hypertension exhibit RAS intrarenal activation and oxidative stress and that the treatment with RAS blockers are able to attenuate these processes.