title: 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 cyclic adenosine monophosphate (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 three groups: the control group, the monocrotaline (M) group (MCT 60 mg/kg), and 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-α, 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.
authors.affiliation: Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hyeryon
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Kwan Chang
authors.initials: KC
authors.lastname: Kim
authors.affiliation: Department of Pathology, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Min-Sun
authors.initials: MS
authors.lastname: Cho
authors.affiliation: Department of Physiology, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Suk-Hyo
authors.initials: SH
authors.lastname: Suh
authors.affiliation: Department of Pediatrics, Ewha Womans University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Hong
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001835:Body Weight; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000188:drug therapy*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D008297:Male; D000077408:Modafinil; D016686:Monocrotaline; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D011312:Pressure; D011651:Pulmonary Artery / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000378:metabolism; D014661:Vasoconstriction
chemical_list: D001559:Benzhydryl Compounds; D019332:Endothelin-1; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C491575:Kcnn4 protein, rat; D044022:Receptor, Endothelin A; D016686:Monocrotaline; D000242:Cyclic AMP; D000077408:Modafinil