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Role of aldosterone synthase, adiponectin, and leptin polymorphisms on hemodynamic parameter and vascular stiffness in obese resistant hypertensives

Grant number: 11/00083-8
Support Opportunities:Regular Research Grants
Duration: July 01, 2011 - December 31, 2013
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal Investigator:Heitor Moreno Junior
Grantee:Heitor Moreno Junior
Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated researchers:Caroline Demacq Souza Tarlá


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. In 2008, the American Heart Association (AHA) added to this hypertensive group those patients who require four or more classes of antihypertensive drugs to achieve blood pressure control. Recently (2010) 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. For example, the decrease in adiponectin is associated with endothelial dysfunction and vasoconstriction. Leptin, in turn, increases the activity of the sympathetic nervous system causing, among other effects, aldosterone secretion by the adrenal cortex. Elevated levels of aldosterone in association with obesity and insulin resistance resulting in pro-inflammatory and pro-oxidants effects which implicated in the development of resistant hypertension mainly because they lead to arterial stiffness in addition to sodium retention with expansion of blood volume. 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. Finally, it has been shown that polymorphisms in adiponectin, leptin and aldosterone synthase genes may have clinically relevant polymorphisms that can be associated to resistance to antihypertensive therapy. 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, by comparing allele frequencies and genotype among controlled and uncontrolled resistant hypertensive patients. In this study will be included 125 resistante hypertensive patients from the Ambulatory of Resistant Hypertension HC-FCM/UNICAMP, proven pharmacological and not pharmacological adherence. They will be divided in two subgroups: 1 - controlled resistant hypertensives, 2 - uncontrolled resistant hypertensives. The noninvasive hemodynamic evaluation will be conducted by Finometer system (Finapres, Amsterdam, Netherlands) and the arterial stiffness related parameters will be obtained by analyzing the pulse wave velocity using the Sphygmocor CPV system (AtCor Medical, USA). 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. Moreover, it is expected that the adipose tissue participation in regulating the production/secretion of aldosterone in patients with resistant hypertension may be better understood by studying the pathophysiology of this syndrome. (AU)

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