Related Experiment Video
Updated: May 14, 2026
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
Transforming growth factor-β inhibition and endothelin receptor blockade in rats with monocrotaline-induced pulmonary
Aikaterini J Megalou1, Chryssoula Glava, Agapi D Vilaeti
1Department of Cardiology, Medical School, University of Ioannina, Ioannina, Greece.
Abstract:
Transforming growth factor-β (TGF-β) inhibition is an investigational therapy for pulmonary arterial hypertension with promising results in experimental studies. The present work compared this approach with endothelin-receptor blockade and evaluated the effects of combined administration. Pulmonary arterial hypertension was induced by single monocrotaline injection (60 mg/kg) in 75 Wistar rats and 15 rats served as controls. Intervention groups consisted of treatment with an antibody against TGF-β-ligand, bosentan, both or none, initiated four weeks after monocrotaline injection. Right ventricular systolic pressure, pulmonary vascular remodeling, and exercise tolerance were evaluated eight weeks after monocrotaline injection. Either treatment, alone or in combination, lowered mortality. Comparable efficacy was found in the three treatment groups in terms of right ventricular systolic pressure (~45% decrease) and hypertrophy (~30% decrease), as well as exercise capacity. The three treatment groups equally ameliorated pulmonary vascular remodeling, evidenced by decreased vessel-wall thickness (in vessels 50-200 μm) and a smaller number of pre-capillary arterioles (< 50 μm) with a muscularized media. Treatment either with an antibody against TGF-β or with endothelin receptor blockade are equally effective in experimental pulmonary hypertension. Their combination provides no added benefit, indicating common mechanisms of action.
Insights
Transforming growth factor-β (TGF-β) inhibition and endothelin-receptor blockade show similar efficacy in treating experimental pulmonary arterial hypertension. Combining these therapies offers no additional benefit, suggesting overlapping mechanisms of action.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Experimental Medicine
Background:
- Pulmonary arterial hypertension (PAH) is a severe condition with limited treatment options.
- Transforming growth factor-β (TGF-β) inhibition is an emerging therapeutic strategy for PAH.
- Endothelin-receptor blockade is an established treatment for PAH.
Purpose of the Study:
- To compare the efficacy of TGF-β inhibition with endothelin-receptor blockade in a rat model of PAH.
- To evaluate the effects of combining these two therapeutic approaches.
Main Methods:
- Pulmonary arterial hypertension was induced in Wistar rats using monocrotaline.
- Rats were treated with an anti-TGF-β antibody, bosentan, both, or neither.
- Hemodynamic parameters, cardiac hypertrophy, exercise tolerance, and pulmonary vascular remodeling were assessed.
Main Results:
- All treatment groups, including monotherapies and combination therapy, reduced mortality.
- Comparable improvements were observed in right ventricular systolic pressure, hypertrophy, and exercise capacity across all treatment groups.
- Pulmonary vascular remodeling, including vessel-wall thickness and media-layer thickness in arterioles, was similarly ameliorated by all interventions.
Conclusions:
- Both TGF-β inhibition and endothelin-receptor blockade are equally effective in experimental PAH.
- Combination therapy does not provide additive benefits over monotherapy.
- These findings suggest that TGF-β inhibition and endothelin-receptor blockade share common underlying mechanisms in PAH treatment.
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