title: The beneficial impact of fasudil and sildenafil on monocrotaline-induced pulmonary hypertension in rats: a hemodynamic and biochemical study.
abstract: Pulmonary arterial hypertension (PAH) still cannot be cured effectively, hence the search for novel treatments continues. The effects of sildenafil (25 mg/kg body weight) and fasudil (30 mg/kg body weight) given alone or in combination, on normalization of right ventricular pressure (RVP), right ventricle mass, as well as the levels of several biomarkers (HDL-C, BNP, VEGF-A), were assessed in a rat model of monocrotaline (MCT)-induced PAH. MCT (60 mg/kg body weight) induced clear PAH in male Wistar rats. After 21 days, a significant decrease in RVP accompanied by a reduction of right ventricular hypertrophy - a significant decrease in the right ventricle/left ventricle plus septum ratio - as a result of sildenafil or fasudil administration was assessed. The administration of fasudil and sildenafil alone or in combination caused a significant decrease in plasma BNP level as compared to MCT-treated rats. Fasudil alone or with sildenafil, but not sildenafil alone, significantly increased HDL-C level as compared to MCT-treated rats. Fasudil and sildenafil given alone or in combination caused a significant increase in plasma VEGF-A level as compared to rats exposed to MCT.
authors: Department of Biopharmacy, Medical University of Łódź, Łódź, Poland. magdalena.jasinska-stroschein@umed.lodz.pl
authors: Magdalena
authors: M
authors: Jasińska-Stroschein
authors: Jacek
authors: J
authors: Owczarek
authors: Anna
authors: A
authors: Łuczak
authors: Daria
authors: D
authors: Orszulak-Michalak
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood; D004359:Drug Therapy, Combination; D065627:Familial Primary Pulmonary Hypertension; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D016686:Monocrotaline; D020097:Natriuretic Peptide, Brain / Q000097:blood; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors*
chemical_list: D008076:Cholesterol, HDL; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011687:Purines; D013450:Sulfones; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D020097:Natriuretic Peptide, Brain; D016686:Monocrotaline; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000068677:Sildenafil Citrate; D054460:rho-Associated Kinases; C049347:fasudil