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
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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