Role of matrix metalloproteinases 2 and 9 in the vascular alterations associated with the 2k-1c model of arterial hypertension: effects of Aliskiren versus Losartan

• Grant number: 10/02514-3
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2010
• End date: July 31, 2012
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Jose Eduardo Tanus dos Santos
• Grantee: Jose Eduardo Tanus dos Santos
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Alisson Martins de Oliveira

Abstract

The renin-angiotensin system plays an important role in the vascular modifications associated with arterial hypertension, and activation of angiotensin type 1 receptors by angiotensin II is associated with the vascular changes found in hypertension. Recent studies showed that rennin and pro-renin may interact with membrane receptors known as (pro)renin ((P)RR), which are present in smooth muscle cells and cardiomiocytes. This interaction results in significant increases in tissue angiotensin formation. Studies in animal models of hypertension showed that the pharmacological inhibition of renin reduces the tissue levels of angiontensin and pro-fibrotic factores. These effects were independent of the reduction in plasma angiontensin concentrations, thus suggesting the involvement of (P)RR receptors in hypertension. We have shown that matrix metalloproteinases (MMPs) may also play a role in the cardiovascular alterations found in hypertension. In this respect, studies have shown that increased MMPs activities may be associated with angiotensin-dependent and independent effects. This project focuses the hypothesis that prorenin and renin inhibition could produce more clear effects on MMPs than AT1 receptors antagonists, thus allowing more intense attenuation of the vascular alterations associated with hypertension. Therefore, we intend to evaluate he effects of renin inhibition e of angiotensin AT1 receptors on the vascular modifications mediated by MMP-2 and MMP-9. In addition, we will examine biochemical, molecular and structural markers. (AU)