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Updated: May 1, 2026
Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Concurrent rho-kinase and tyrosine kinase platelet-derived growth factor inhibition in experimental pulmonary
Magdalena Jasińska-Stroschein1, Jacek Owczarek, Paulina Plichta
1Department of Biopharmacy, Medical University of Łódź, Łódź, Poland.
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.
Insights
Combining fasudil (Rho-kinase inhibitor) and imatinib (PDGF receptor inhibitor) significantly improved pulmonary arterial hypertension (PAH) in rats, reducing right ventricular pressure and hypertrophy more than either drug alone.
Area of Science:
- Pharmacology
- Cardiovascular Research
- Pulmonary Hypertension
Background:
- Pulmonary arterial hypertension (PAH) is a severe condition.
- Targeting Rho-kinase and platelet-derived growth factor (PDGF) receptor pathways are potential therapeutic strategies for PAH.
Purpose of the Study:
- To investigate the combined effects of fasudil (Rho-kinase inhibitor) and imatinib (PDGF receptor inhibitor) on experimental PAH.
- To determine if this combination therapy offers superior improvement compared to monotherapy.
Main Methods:
- Monocrotaline (MCT)-induced pulmonary hypertension model in male rats.
- Rats were treated with imatinib, fasudil, or their combination for 14 days post-MCT injection.
- Evaluated hemodynamics, right ventricle hypertrophy, PDGF levels, and Rho-kinase (ROCK) activity.
Main Results:
- Combined fasudil and imatinib significantly reduced right ventricular pressure and hypertrophy compared to individual treatments.
- The combination therapy led to a greater decrease in plasma PDGF-BB levels than either drug alone.
- Fasudil and imatinib combination demonstrated enhanced efficacy in reversing MCT-induced PAH markers.
Conclusions:
- Inhibiting Rho-kinase with fasudil alongside PDGF receptor inhibition with imatinib provides significant improvement in PAH.
- The enhanced therapeutic effect is likely due to the additive impact on reducing PDGF-induced effects and Rho-kinase activity.
- This combination therapy represents a promising strategy for managing pulmonary arterial hypertension.
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