Modafinil improves monocrotaline-induced pulmonary hypertension rat model

Abstract Pulmonary arterial hypertension (PAH) progressively leads to increases in pulmonary vasoconstriction. Modafinil plays a role in vasorelaxation and blocking KCa3.1 channel with a result of elevating intracellular cAMP levels. The purpose of this study is to evaluate the effects on modafinil in monocrotaline (MCT)-induced PAH rat. The rats were separated into 3 groups: the control group; the monocrotaline (M) group (MCT 60 mg/kg); the modafinil (MD) group (MCT 60 mg/kg + modafinil. Reduced right ventricular pressure (RVP) was observed in the MD group. Right ventricular hypertrophy was improved in the MD group. Reduced number of intra-acinar pulmonary arteries and medial wall thickness were noted in the MD group. After the administration of modafinil, protein expressions of endothelin-1 (ET-1), endothelin receptor A (ERA) and KCa3.1 channel were significantly reduced. Modafinil suppressed pulmonary artery smooth muscle cell (PASMC) proliferation via cAMP and KCa3.1 channel. Additionally, we confirmed protein expressions such as Bcl-2-associated X, vascular endothelial growth factor, tumor necrosis factor-a and interleukin-6 were reduced in the MD group. Modafinil improved PAH by vasorelaxation and a decrease in medial thickening via ET-1, ERA and KCa3.1 down regulation. This is a meaningful study of a modafinil in PAH model.Pediatric Research (2016); doi:10.1038/pr.2016.38.