title: Rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension.
abstract: BACKGROUND
  It remains controversial whether statins have a beneficial effect on pulmonary arterial hypertension (PAH). This study is intended to evaluate whether statin, co-administered with Rho-kinase inhibitor, could enhance its efficacy. Although Rho-kinase inhibitors, including fasudil, have been reported to improve pulmonary hypertension in experimental and clinical studies, the combination of these agents has not been tested in the treatment of pulmonary hypertension (PH).
  
  
  METHODS
  The effects of such a regimen on hemodynamics, right ventricle hypertrophy, and Rho-associated protein kinase (ROCK) activity in experimental monocrotaline (MCT)-induced pulmonary hypertension were examined. Fourteen days after monocrotaline injection (60 mg/kg), male rats were treated orally for another 14 days with fasudil (15 mg/kg per day), or with a combination of fasudil + rosuvastatin (10 mg/kg per day).
  
  
  RESULTS
  The drug combination reversed the MCT-induced increase in right ventricle pressure (RVP) and reduced right ventricular hypertrophy (RV/LV + S ratio) more than Rho kinase inhibitor alone. The simultaneous administration of fasudil and rosuvastatin caused a further decrease of RhoA kinase activity in isolated lung tissues as compared to fasudil alone.
  
  
  CONCLUSIONS
  The results indicate that rosuvastatin intensifies the beneficial effects of Rho-kinase inhibitor on the Rho/Rho-kinase pathway and such a combination may represent an option for the treatment of pulmonary arterial hypertension.
authors.affiliation: Department of Biopharmacy, Medical University of Lodz, Lodz, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jasińska-Stroschein
authors.affiliation: Department of Biopharmacy, Medical University of Lodz, Lodz, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Owczarek
authors.affiliation: Department of Biopharmacy, Medical University of Lodz, Lodz, Poland.
authors.forename: Urszula
authors.initials: U
authors.lastname: Sołtysiak
authors.affiliation: Department of Biopharmacy, Medical University of Lodz, Lodz, Poland.
authors.forename: Daria
authors.initials: D
authors.lastname: Orszulak-Michalak
keywords: Rho/Rho kinase pathway; combination therapy; fasudil; pulmonary hypertension; rosuvastatin