Impact of polymorphisms of adiponectin, leptin and aldosterone synthase on haemodynamic profile and anti-hypertensive response in resistant hypertension.

• Grant number: 12/01386-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2012
• End date: June 30, 2014
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: Heitor Moreno Junior
• Grantee: Vanessa Fontana
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated scholarship(s): 12/21782-4 - Genetic polymorphisms associated with cardiovascular outcomes and blood pressure control in resistant hypertension of INVEST-GENE substudy (the international Verapamil-Trandolapril study), BE.EP.PD

Abstract

Resistant Hypertension is characterized as the presence of hypertension and concomitant use of three different classes of antihypertensive drugs with at least one of these agents been a diuretic, or patients who require four or more classes of antihypertensive drugs to achieve blood pressure control. Recently we show that such subgroups: resistant uncontrolled and resistant controlled are quite distinct in several characteristics, especially regarding the degree of obesity, the prevalence of aldosteronism and arterial stiffness. Currently it has been largely discussed the influence of obesity both in hypertension and in resistance to antihypertensive therapy. Hormones secreted by adipose tissue, such as adiponectin and leptin, may have direct and indirect effects regardless of obesity on blood pressure control. In addition to conventional environmental factors is known that genetic factors influence the mechanisms of blood pressure control and may play a role in determining resistance to antihypertensive drugs. This project aims to assess whether polymorphisms in aldosterone synthase, adiponectin and leptin are associated with specific hemodynamic patterns in patients with resistant hypertension as well as evaluating the association of these polymorphisms with resistance to antihypertensive therapy. In this study will be included 125 obese resistante hypertensive patients from the Ambulatory of Resistant Hypertension HC-FCM/UNICAMP. The hemodynamic evaluation and the arterial stiffness related parameters will be obtained by qualified professional. The genotyping will be performed by real time PCR using TaqMan detection system (Applied Biosystems, Foster City, U.S.). The plasma concentrations of adiponectin and leptin will be determined by ELISA. The identification of genetic markers as well as the characterization of the hemodynamic profile and hormonal (aldosterone, plasma leptin and adiponectin) contribute to improve the understanding of drug resistance in patients with resistant hypertension.