Therapeutic effect of sorafenib in monocrotaline-induced pulmonary arterial hypertension rats

ABSTRACT

Sorafenib is an inhibitor of multi-kinases including tyrosine and serine/threonine kinases. This study investigated the efficacy and safety of sorafenib, an inhibitor of multi-kinases, for the treatment of pulmonary arterial hypertension (PAH), in monocrotaline (MCT)-induced PAH rat models. PAH was induced by subcutaneous (sc) injection of 60 mg/ kg monocrotaline (MCT) dissolved in 0.5 N HCl. Rats were assigned into the following groups 1) control (C) group, 2) monocrotaline (M) group, and 3) sorafenib (S) group (MCT injection + sorafenib injection group). Rats in the treatment groups received a daily oral gavage of 2.5 mg/kg sorafenib for seven days. Our results showed that sorafenib treatment reduced systolic pulmonary artery pressure (SPAP) in PAH rats, and improved right ventricular (RV) hypertrophy, an indicator of RV pressure overload caused by elevated pulmonary artery pressure. In addition, the number of intraacinar arteries and medial wall thickening in pulmonary arterioles (an index of vascular remodeling) were decreased. Our results revealed that sorafenib reduced ventricular hypertrophy and the expression of fibrosis. These results support the notion that sorafenib improves the functional properties of RV, thereby highlighting its potential benefits for heart and lung impairment

RESUMEN

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