title: Bucindolol improves right ventricle function in rats with pulmonary arterial hypertension through the reversal of autonomic imbalance.
abstract: Pulmonary arterial hypertension (PAH) is characterised by an elevation in afterload imposed on the right ventricle (RV), leading to hypertrophy and failure. The autonomic nervous system (ANS) plays a key role in the progression to heart failure, and the use of beta-blockers attenuates this process. The aim of this study was to verify the role of bucindolol, aβ1-, β2- and α1-blocker, on the ANS, and its association with RV function in rats with PAH. Male Wistar rats were divided into four groups: control, monocrotaline, control+bucindolol, and monocrotaline+bucindolol. PAH was induced by a single intraperitoneal injection of monocrotaline (60mg/kg). After two weeks, animals were treated for seven days with bucindolol (2mg/kg/day i.p.) or vehicle. At the end of the treatment, animals underwent echocardiographic assessment, catheterisation of the femoral artery and RV, and tissue collection for morphometric and histological evaluation. In the monocrotaline+bucindolol group, there was a decrease in mean pulmonary artery pressure (33%) and pulmonary congestion (21%), when compared to the monocrotaline. Bucindolol treatment also reduced RV pleomorphism, necrosis, fibrosis and infiltration of inflammatory cells. An improvement in RV systolic function was also observed in the monocrotaline+bucindolol group compared to the monocrotaline. In addition, bucindolol promoted a decrease in the cardiac sympathovagal balance (93%) by reducing sympathetic drive (70%) and increasing parasympathetic drive (142%). Bucindolol also reduced blood pressure variability (75%). Our results show that the beneficial effects from bucindolol treatment appeared to be a consequence of the reversal of monocrotaline-induced autonomic imbalance.
authors.affiliation: Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rio Grande do Sul, Brazil. Electronic address: bruna.gazzi@hotmail.com.
authors.forename: Bruna Gazzi de
authors.initials: BG
authors.lastname: Lima-Seolin
authors.affiliation: Laboratory of Pharmacology and Physiology, Universidade de Caxias do Sul (UCS), Rio Grande do Sul, Brazil. Electronic address: rcolombo1@ucs.br.
authors.forename: Rafael
authors.initials: R
authors.lastname: Colombo
authors.affiliation: Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rio Grande do Sul, Brazil. Electronic address: jpbonetto@gmail.com.
authors.forename: Jéssica Hellen Poletto
authors.initials: JHP
authors.lastname: Bonetto
authors.affiliation: Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rio Grande do Sul, Brazil. Electronic address: rayca_shumi@hotmail.com.
authors.forename: Rayane Brinck
authors.initials: RB
authors.lastname: Teixeira
authors.affiliation: Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rio Grande do Sul, Brazil. Electronic address: luizadonatti@hotmail.com.
authors.forename: Luiza Mezzomo
authors.initials: LM
authors.lastname: Donatti
authors.affiliation: Institute of Science and Technology (ICT), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil.
authors.forename: Karina Rabello
authors.initials: KR
authors.lastname: Casali
authors.affiliation: Research Institute for Multicenter Studies (IPCEM), Universidade de Caxias do Sul (UCS), Rio Grande do Sul, Brazil. Electronic address: aeggodoy@gmail.com.
authors.forename: Alessandra Eifler Guerra
authors.initials: AEG
authors.lastname: Godoy
authors.affiliation: Research Institute for Multicenter Studies (IPCEM), Universidade de Caxias do Sul (UCS), Rio Grande do Sul, Brazil. Electronic address: ielitvin@ucs.br.
authors.forename: Isnard Elman
authors.initials: IE
authors.lastname: Litvin
authors.affiliation: Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rio Grande do Sul, Brazil. Electronic address: schenkel.paulo@gmail.com.
authors.forename: Paulo Cavalheiro
authors.initials: PC
authors.lastname: Schenkel
authors.affiliation: Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rio Grande do Sul, Brazil. Electronic address: 00029242@ufrgs.br.
authors.forename: Alex Sander da
authors.initials: ASD
authors.lastname: Rosa Araujo
authors.affiliation: Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Institute of Basic Health Science (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Rio Grande do Sul, Brazil. Electronic address: belklein@ufrgs.br.
authors.forename: Adriane
authors.initials: A
authors.lastname: Belló-Klein
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D004562:Electrocardiography; D006352:Heart Ventricles / Q000187:drug effects* / Q000503:physiopathology*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D011412:Propanolamines; D016686:Monocrotaline; C024307:bucindolol
keywords: Beta-blocker; Bucindolol; Monocrotaline; Right heart failure; Spectral analysis