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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 in English | WPRIM | ID: wpr-759469
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Oxidoreductases / Arteries / Arterioles / Body Weight / Victoria / Gene Expression / Blotting, Western / Endothelins / Monocrotaline / Receptors, Endothelin Type of study: Prognostic study Limits: Animals / Humans Country/Region as subject: Oceania Language: English Journal: Korean Circulation Journal Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Oxidoreductases / Arteries / Arterioles / Body Weight / Victoria / Gene Expression / Blotting, Western / Endothelins / Monocrotaline / Receptors, Endothelin Type of study: Prognostic study Limits: Animals / Humans Country/Region as subject: Oceania Language: English Journal: Korean Circulation Journal Year: 2019 Type: Article