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Updated: Aug 8, 2026
The Left Pneumonectomy Combined with Monocrotaline or Sugen as a Model of Pulmonary Hypertension in Rats
Published on: March 8, 2019
PAF receptor blockade inhibits lung vascular changes in the rat monocrotaline model
1Cardiovascular Pulmonary Research Laboratory, University of Colorado Health Sciences Center, Denver 80262.
Abstract:
We recently reported that platelet-activating factor (PAF) levels increased in lung tissue after 1 subcutaneous injection of monocrotaline (MCT) (which causes lung injury), and, further, that treatment with PAF antagonists reduced pulmonary hypertension in this chronic lung injury rat model [15]. In the present study, we examined the effect of WEB 2170, a specific PAF antagonist, on MCT-induced pulmonary vascular remodeling. At 3 weeks after MCT injection, pulmonary hypertension in the animals was associated with an increase in the vessel wall thickness of the muscular arteries, reduction in number of peripheral arterioles, and right ventricular hypertrophy. In WEB 2170-treated rats, these changes were significantly less severe when compared with those observed in MCT-treated rats. In MCT-treated rats, there were significant increases in in vitro [3H]thymidine incorporation and accumulation of hydroxyproline in the lung tissue, and these changes were inhibited by WEB 2170 treatment. Our results suggest that PAF or a PAF-dependent sequence of events is involved in MCT-induced lung vascular remodeling.
Insights
Platelet-activating factor (PAF) plays a role in monocrotaline-induced lung injury. A PAF antagonist, WEB 2170, significantly reduced pulmonary hypertension and vascular remodeling in rats.
Area of Science:
- Pulmonary Hypertension Research
- Vascular Biology
- Pharmacology
Background:
- Platelet-activating factor (PAF) levels increase in lung tissue following monocrotaline (MCT) administration.
- PAF antagonists have previously shown potential in reducing pulmonary hypertension in chronic lung injury models.
Purpose of the Study:
- To investigate the efficacy of WEB 2170, a specific PAF antagonist, in mitigating MCT-induced pulmonary vascular remodeling.
- To further elucidate the role of PAF in the pathogenesis of MCT-induced pulmonary hypertension.
Main Methods:
- Rats were injected with monocrotaline (MCT) to induce lung injury and pulmonary hypertension.
- One group received WEB 2170 treatment, while another served as a control.
- Pulmonary vascular remodeling, right ventricular hypertrophy, and lung tissue markers ([3H]thymidine incorporation, hydroxyproline) were assessed.
Main Results:
- MCT-induced pulmonary hypertension was characterized by increased arterial wall thickness, reduced arteriole number, and right ventricular hypertrophy.
- WEB 2170 treatment significantly attenuated these MCT-induced changes.
- WEB 2170 inhibited increases in [3H]thymidine incorporation and hydroxyproline accumulation in lung tissue.
Conclusions:
- PAF or PAF-dependent pathways are implicated in the vascular remodeling associated with MCT-induced lung injury.
- WEB 2170 demonstrates a protective effect against MCT-induced pulmonary hypertension and vascular remodeling.
