title: Concurrent rho-kinase and tyrosine kinase platelet-derived growth factor inhibition in experimental pulmonary hypertension.
abstract: BACKGROUND
  We hypothesized that inhibition of Rho-kinase by fasudil, together with tyrosine kinase platelet-derived growth factor (PDGF) receptor inhibition by imatinib, results in greater pulmonary arterial hypertension (PAH) improvement.
  
  
  METHODS
  The effects of such regimens were investigated on hemodynamics, right ventricle hypertrophy, PDGF and ROCK in experimental monocrotaline (MCT)-induced pulmonary hypertension. Fourteen days after MCT injection, male rats were treated orally for another 14 days with imatinib, fasudil or their combination.
  
  
  RESULTS
  Concurrent imatinib and fasudil administration reversed an MCT-induced increase in right ventricular pressure more than either drug alone and decreased right ventricle hypertrophy (right ventricle weight to left ventricle plus septum weight ratio) significantly. The simultaneous administration of fasudil and imatinib caused a further decrease in plasma PDGF-BB levels compared to either drug alone.
  
  
  CONCLUSIONS
  Inhibition of Rho-kinase by fasudil in addition to tyrosine kinase PDGF inhibition by imatinib can result in further PAH improvement. Such outcome may result from additional impact of the Rho-kinase inhibitor on the decrease in PDGF-induced effects.
authors.affiliation: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jasińska-Stroschein
authors.forename: Jacek
authors.initials: J
authors.lastname: Owczarek
authors.forename: Paulina
authors.initials: P
authors.lastname: Plichta
authors.forename: Daria
authors.initials: D
authors.lastname: Orszulak-Michalak
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000077214:Becaplermin; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy; D000068877:Imatinib Mesylate; D008297:Male; D016686:Monocrotaline / Q000633:toxicity; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D017725:Ventricular Pressure / Q000187:drug effects; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D020574:Proto-Oncogene Proteins c-sis; D011743:Pyrimidines; D000077214:Becaplermin; D016686:Monocrotaline; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000068877:Imatinib Mesylate; C099852:PDGF receptor tyrosine kinase; D017479:Receptors, Platelet-Derived Growth Factor; D054460:rho-Associated Kinases; C049347:fasudil