Influence of polymorphisms of genes of adrenergic receptors, nitric oxide synthase and bradykinin in peripheral vasodilation and functional capacity of patients with heart failure

• Grant number: 11/20007-4
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2012
• End date: February 28, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Alfredo José Mansur
• Grantee: Alfredo José Mansur
• Host 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
• Associated researchers: Alexandre da Costa Pereira ; Carlos Eduardo Negrão ; Gustavo Ferreira Correia ; José Eduardo Krieger ; Maria Urbana Pinto Brandão Rondon ; Rafael Amorim Belo Nunes

Abstract

The functional capacity of patients with heart failure may be influenced by clinical and metabolic characteristics, vascular function and genetic factors. We hypothesized that the polymorphisms of genes of adrenergic receptors, nitric oxide synthase and bradykinin may influence peripheral vasodilation and functional capacity of patients with heart failure. The aim of this study to evaluate functional capacity of outpatients with heart failure relative to clinical variables, to forearm blood flow measured by venous occlusion plethysmography and to functional variants of genes of alpha1-adrenergic receptor (Arg347Cys), alpha2-adrenergic receptor (C1291G), alpha2B-adrenergic receptor (12Glu9), alpha2C-adrenergic receptor (Del 322-325), beta-2 adrenergic receptor (Gly16Arg), genes of the nitric oxide synthase (-786T / C and Glu298Arg) and bradykinin (BK2R). The sample size was calculated in 505 patients, considering 95% power to estimate a change of forearm muscle blood flow of 0.05 ml.min-1. 100 ml tissue -1. The forearm muscle vasodilator response will be evaluated by the forearm muscle blood flow at rest and during isometric exercise (handgrip maneuver). The functional capacity will be evaluated by cardiopulmonary exercise test on a electromagnetic bicycle. Genotyping of the following polymorphisms will be perrformed: alpha1-adrenergic receptor (Arg347Cys), alpha2-adrenergic receptor (C1291G), alfa2B-adrenergic receptor (12Glu9), alfa2C-adrenergic receptor (Del 322-325), beta-2 adrenergic receptor (Gly16Arg), oxide synthase (-786T / C and Glu298Arg) and bradykinin (BK2R). We will study the influence of polymorphisms of genes of adrenergic receptors, nitric oxide synthase and bradykinin in peripheral vasodilation and functional capacity of patients with heart failure. (AU)