Bucindolol attenuates the vascular remodeling of pulmonary arteries by modulating the expression of the endothelin-1 A receptor in rats with pulmonary arterial hypertension
Autor: | Bruna Gazzi de Lima-Seolin, Jéssica Hellen Poletto Bonetto, Alessandra Eifler Guerra Godoy, Rafael Colombo, Isnard Elman Litvin, Rafael Oliveira Fernandes, Matheus Mittmann Hennemann, Paulo Cavalheiro Schenkel, Adriane Belló-Klein, Neelam Khaper, Rayane Brinck Teixeira, Alex Sander da Rosa Araujo |
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Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Nitric Oxide Synthase Type III Hypertension Pulmonary Adrenergic beta-Antagonists Pulmonary Artery Vascular Remodeling 030204 cardiovascular system & hematology Propanolamines 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine.artery medicine Animals Rats Wistar Endothelial dysfunction Pharmacology Monocrotaline biology business.industry Nitrotyrosine Bucindolol General Medicine Receptor Endothelin A medicine.disease Receptor Endothelin B Endothelin 1 Rats Nitric oxide synthase Disease Models Animal Oxidative Stress 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Echocardiography Ventricle Pulmonary artery Vascular resistance biology.protein business |
Zdroj: | Biomedicine & Pharmacotherapy. 99:704-714 |
ISSN: | 0753-3322 |
Popis: | The aim of this study was to investigate the role of the ß-adrenergic blocker bucindolol on endothelial dysfunction and pulmonary vascular remodeling in rats with pulmonary arterial hypertension (PAH). Male Wistar rats were divided into four groups: control, monocrotaline (MCT), control?+?bucindolol and monocrotaline?+?bucindolol (MCT?+?BCD). PAH was induced by an injection of monocrotaline (60?mg/kg i.p.). After two weeks, the animals were treated for seven days with bucindolol (2?mg/kg/day i.p.) or vehicle. Echocardiography was performed upon treatment completion to analyze pulmonary vascular resistance (PVR) and right ventricle (RV) myocardial performance index. Lungs were collected for oxidative stress and western blot analysis, and the pulmonary artery was analyzed for histological and immunohistochemical parameters. The MCT?+?BCD group showed a decrease (32%) in the protein expression of endothelin-1 type A receptor (ETAR) and in the ratio of ETA/endothelin-1 type B receptor (ETBR) (62%) as compared to the MCT group. Bucindolol treatment did not alter oxidative stress, as determined by lipid peroxidation analysis and antioxidant enzyme activities and expression, endothelial nitric oxide synthase immunocontent and decreased nitrotyrosine levels. Moreover, bucindolol improved vascular remodeling of the pulmonary artery in the MCT?+?BCD group by decreasing (21%) PVR and increasing RV workload in relation to MCT. |
Databáze: | OpenAIRE |
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