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Effects of the TNF-alpha inhibiton on blood pressure, hemodynamic parameters and biomarkers in resistant hypertension

Grant number: 15/17151-7
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): December 01, 2015
Effective date (End): March 31, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Heitor Moreno Junior
Grantee:Ana Paula Cabral de Faria Modolo
Host Institution: Hospital de Clínicas (HC). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):16/02316-3 - Effect of transcranial direct current stimulation on hemodynamic parameters in resistant hypertensive subjects, BE.EP.PD

Abstract

Resistant hypertension (RH) is characterized by high blood pressure (BP) in spite of concurrent use of three or more antihypertensive agents of different classes, combined at optimal doses. Currently it has been largely discussed the influence of inflammation in RH. The BP variation promotes increased expression of pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukins 1 and 6. It was showed that treatment with TNF-alpha inhibitor improves BP and endothelial function, and reduces arterial stiffness in patients with rheumatoid arthritis. Recently, it was demonstrated that TNF-alpha levels are increased in RH subjects compared to normotensives. This project aims to assess whether the acute inhibition of TNF-alpha reduces BP levels, as well as changes hemodynamic parameters, target organ damage and inflammatory biomarkers in RH. This crossover, double-blind study will include 12 resistant hypertensive subjects -regularly followed at the Outpatient Resistant Hypertension Clinic/UNICAMP - which will randomized assigned to (1) serum infusion followed by infliximab infusion (TNF-alpha inhibitor, 3 mg/kg) and (2) infliximab followed by serum, for two hours and washout of the 40-day period between both infusions. Office, central and ABPM BP, inflammatory biomarkers, cardiac hypertrophy (echocardiography), endothelial function by flow-mediated dilation, arterial stiffness by pulse wave velocity (Sphygmocor CPV system) will be determined before and after 7 days of infusion. Hemodynamic parameters will be simultaneously assessed during infusions. The plasma concentrations of TNF-alpha, ILs-1, -6 e -10, monocyte chemoattractant protein-1, cGMP, chemerin and adiponectin will be determined by ELISA and of nitric oxide by chemiluminescence. It is expected that the TNF-alpha inhibition regulates BP levels, which may allow a better rational approach for the RH treatment as well as prevent target organ damage.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DE FARIA, ANA PAULA; RITTER, V, ALESSANDRA M.; SANTA-CATHARINA, ARTHUR; SOUZA, DEBORA P.; NASERI, ESTEPHANIA P.; BERTOLO, MANOEL B.; PIOLI, MARIANA RODRIGUES; CARVALHO, CAIO C.; MODOLO, RODRIGO; MORENO, HEITOR. Efeitos da Terapia com Anti-TNF alfa na Pressão Arterial em Pacientes com Hipertensão Resistente: Um Estudo Piloto Randomizado, Duplo-Cego e Controlado por Placebo. Arquivos Brasileiros de Cardiologia, v. 116, n. 3, p. 443-451, . (15/17151-7)

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