Lima-Seolin Bruna Gazzi de, Colombo Rafael, Bonetto Jéssica Hellen Poletto, Teixeira Rayane Brinck, Donatti Luiza Mezzomo, Casali Karina Rabello, Godoy Alessandra Eifler Guerra, Litvin Isnard Elman, Schenkel Paulo Cavalheiro, Rosa Araujo Alex Sander da, Belló-Klein Adriane
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.
Laboratory of Pharmacology and Physiology, Universidade de Caxias do Sul (UCS), Rio Grande do Sul, Brazil.
Eur J Pharmacol. 2017 Mar 5;798:57-65. doi: 10.1016/j.ejphar.2016.12.028. Epub 2016 Dec 21.
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.
肺动脉高压（PAH）的特征是右心室（RV）后负荷升高，导致肥厚和衰竭。自主神经系统（ANS）在心力衰竭的进展中起关键作用，使用β受体阻滞剂可减轻这一过程。本研究的目的是验证β1、β2和α1受体阻滞剂布新洛尔对ANS的作用及其与PAH大鼠右心室功能的关系。将雄性Wistar大鼠分为四组：对照组、野百合碱组、对照组+布新洛尔组和野百合碱+布新洛尔组。通过单次腹腔注射野百合碱（60mg/kg）诱导PAH。两周后，动物用布新洛尔（2mg/kg/天，腹腔注射）或赋形剂治疗7天。治疗结束时，对动物进行超声心动图评估、股动脉和右心室插管，并收集组织进行形态计量学和组织学评估。与野百合碱组相比，野百合碱+布新洛尔组的平均肺动脉压降低了33%，肺淤血减少了21%。布新洛尔治疗还减少了右心室的多形性、坏死、纤维化和炎性细胞浸润。与野百合碱组相比，野百合碱+布新洛尔组的右心室收缩功能也有所改善。此外，布新洛尔通过降低交感神经驱动（70%）和增加副交感神经驱动（142%），使心脏交感迷走平衡降低了93%。布新洛尔还降低了血压变异性（75%）。我们的结果表明，布新洛尔治疗的有益效果似乎是野百合碱诱导的自主神经失衡逆转的结果。
