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PAF antagonists inhibit monocrotaline-induced lung injury and pulmonary hypertension

S Ono1, N F Voelkel

  • 1Department of Medicine, University of Colorado Health Sciences Center, Denver 80262.

Journal of Applied Physiology (Bethesda, Md. : 1985)
|December 1, 1991
PubMed

Insights

Platelet-activating factor (PAF) antagonists reduced lung injury and pulmonary hypertension in rats. Targeting PAF may prevent inflammation and vascular damage in lung disease.

Area of Science:

  • Pulmonary Medicine
  • Inflammation Research
  • Pharmacology

Background:

  • Monocrotaline (MCT) injection in rats causes lung injury, pulmonary hypertension, and right ventricular hypertrophy.
  • Platelet-activating factor (PAF) levels increase in the lungs following MCT administration.
  • PAF is implicated in inflammatory processes and vascular permeability.

Purpose of the Study:

  • To investigate the therapeutic potential of PAF antagonists (WEB 2086 and WEB 2170) in a rat model of MCT-induced lung injury and pulmonary hypertension.
  • To determine the role of PAF in the early vascular leak and chronic inflammatory phases of MCT-induced lung disease.

Main Methods:

  • Rats were injected with monocrotaline (MCT) to induce lung injury.
  • Specific PAF antagonists, WEB 2086 and WEB 2170, were administered at various time points.
  • Pulmonary hypertension, right ventricular hypertrophy, and pulmonary vascular leak were assessed.

Main Results:

  • Treatment with WEB 2086 or WEB 2170 significantly reduced MCT-induced pulmonary hypertension and right ventricular hypertrophy.
  • WEB 2170 administration decreased pulmonary vascular leak at 1 week post-MCT.
  • Early administration of WEB 2086 also attenuated right ventricular hypertrophy.
  • Late administration of WEB 2170 inhibited the progression of right ventricular hypertrophy.

Conclusions:

  • PAF plays a critical role in the early pulmonary vascular leak following MCT injury.
  • The early vascular leak phase is crucial for the development of sustained pulmonary hypertension and right ventricular hypertrophy.
  • PAF contributes to a chronic inflammatory process involving other lipid mediators, exacerbating pulmonary hypertension.
  • PAF antagonists represent a potential therapeutic strategy for mitigating inflammatory lung injury and pulmonary hypertension.

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