Effects of drugs activating NO-cGMP pathway in vascular changes associated with experimental hypertension 2R1C

• Grant number: 10/15861-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2011
• End date: November 30, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Jose Eduardo Tanus dos Santos
• Grantee: Danielle Aparecida Guimarães
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 13/09930-0 - Effects of drugs activating the NO-cGMP pathway on the production of MMPs in cell culture, BE.EP.DR

Abstract

Hypertension is a growing public health problem, being a major factor associated with increased risk of cardiovascular disease. The experimental model of hypertension 2 kidney-1clip (2R1C) causes significant activation of the renin-angiotensin system, and produces vascular changes associated with increased oxidative stress and excessive activation of extracellular matrix metalloproteinases (MMPs). MMPs can be regulated by several processes, mainly by oxidative stress, and increased activation of these proteases, promotes excessive degradation of extracellular matrix components, and thereby causes a pathological vascular remodeling. Statins reduce cholesterol production, and as sildenafil, which is widely used to treat erectile dysfunction and is an inhibitor of phosphodiesterase (PDE5), has beneficial effects called pleiotropic effects. Among these effects include: the improvement in endothelial function, reduced blood pressure, increased NO bioavailability and antioxidant effects. Thus, as the expression/activity of MMPs can be regulated by oxidative stress, drugs such as statins and sildenafil that activate via NO-cGMP and have antioxidant effects could reduce the levels of MMPs and oxidative stress, in addition to pathological vascular remodeling occurred during experimental hypertension 2K1C. Additionally, we analyzed biochemical, molecular and structural groups.