Effect of Ambrisentan Therapy on the Expression of Endothelin Receptor, Endothelial Nitric Oxide Synthase and NADPH Oxidase 4 in Monocrotaline-induced Pulmonary Arterial Hypertension Rat Model
Korean Circulation Journal
; : 866-876, 2019.
Article
em En
| WPRIM
| ID: wpr-759469
Biblioteca responsável:
WPRO
ABSTRACT
BACKGROUND AND OBJECTIVES:
Elevated endothelin (ET)-1 level is strongly correlated with the pathogenesis of pulmonary arterial hypertension (PAH). Expression level of nicotinamide adenine dinucleotide phosphate oxidase (NOX) 4 is increased in the PAH patients. Ambrisentan, a selective endothelin receptor A (ERA) antagonist, is widely used in PAH therapy. The current study was undertaken to evaluate the effects of ambrisentan treatment in the monocrotaline (MCT)-induced PAH rat model.METHODS:
Rats were categorized into control group (C), monocrotaline group (M) and ambrisentan group (Am). The M and Am were subcutaneously injected 60 mg/kg MCT at day 0, and in Am, ambrisentan was orally administered the day after MCT injection for 4 weeks. The right ventricle (RV) pressure was measured and pathological changes of the lung tissues were observed by Victoria blue staining. Protein expressions of ET-1, ERA, endothelial nitric oxide synthase (eNOS) and NOX4 were confirmed by western blot analysis.RESULTS:
Ambrisentan treatment resulted in a recovery of the body weight and RV/left ventricle+septum at week 4. The RV pressure was lowered at weeks 2 and 4 after ambrisentan administration. Medial wall thickening of pulmonary arterioles and the number of intra-acinar arteries were also attenuated by ambrisentan at week 4. Protein expression levels of ET-1 and eNOS were recovered at weeks 2 and 4, and ERA levels recovered at week 4.CONCLUSIONS:
Ambrisentan administration resulted in the recovery of ET-1, ERA and eNOS protein expression levels in the PAH model. However, the expression level of NOX4 remained unaffected after ambrisentan treatment.Palavras-chave
Texto completo:
1
Índice:
WPRIM
Assunto principal:
Oxirredutases
/
Artérias
/
Arteríolas
/
Peso Corporal
/
Vitória
/
Expressão Gênica
/
Western Blotting
/
Endotelinas
/
Monocrotalina
/
Receptores de Endotelina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
País/Região como assunto:
Oceania
Idioma:
En
Revista:
Korean Circulation Journal
Ano de publicação:
2019
Tipo de documento:
Article