Bucindolol improves right ventricle function in rats with pulmonary arterial hypertension through the reversal of autonomic imbalance

Bruna Gazzi de Lima-Seolin, Rafael Colombo, Jéssica Hellen Poletto Bonetto, Rayane Brinck Teixeira, Luiza Mezzomo Donatti, Karina Rabello Casali, Alessandra Eifler Guerra Godoy, Isnard Elman Litvin, Paulo Cavalheiro Schenkel, Alex Sander da Rosa Araujo, Adriane Belló-Klein

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 (60 mg/kg). After two weeks, animals were treated for seven days with bucindolol (2 mg/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.

Original languageEnglish
Pages (from-to)57-65
Number of pages9
JournalEuropean Journal of Pharmacology
Volume798
DOIs
StatePublished - 2017
Externally publishedYes

Keywords

  • Beta-blocker
  • Bucindolol
  • Monocrotaline
  • Right heart failure
  • Spectral analysis

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