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: Magdalena Jasińska-Stroschein, Jacek Owczarek, Anna Łuczak, Daria Orszulak-Michalak
• Journal: Pharmacology (Pharmacology) Vol. 91 Issue 3-4 Pg. 178-84 ( 2013) ISSN: 1423-0313 [Electronic] Switzerland
• PMID: 23428587 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 S. Karger AG, Basel.

Chemical References

• Cholesterol, HDL
• Phosphodiesterase 5 Inhibitors
• Piperazines
• Protein Kinase Inhibitors
• Purines
• Sulfones
• Vascular Endothelial Growth Factor A
• vascular endothelial growth factor A, rat
• Natriuretic Peptide, Brain
• Monocrotaline
• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
• Sildenafil Citrate
• rho-Associated Kinases
• fasudil

Topics

• 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine (administration & dosage, analogs & derivatives)
• Animals
• Cholesterol, HDL (blood)
• Drug Therapy, Combination
• Familial Primary Pulmonary Hypertension
• Hemodynamics (drug effects)
• Hypertension, Pulmonary (blood, chemically induced, drug therapy, physiopathology)
• Male
• Monocrotaline
• Natriuretic Peptide, Brain (blood)
• Phosphodiesterase 5 Inhibitors (administration & dosage)
• Piperazines (administration & dosage)
• Protein Kinase Inhibitors (administration & dosage)
• Purines (administration & dosage)
• Rats
• Rats, Wistar
• Sildenafil Citrate
• Sulfones (administration & dosage)
• Vascular Endothelial Growth Factor A (blood)
• rho-Associated Kinases (antagonists & inhibitors)