Abstract
Monocrotaline (MCT) causes lung inflammatory responses and chronic pulmonary hypertension in rats. Since platelet-activating factor (PAF), a potent mediator of inflammation, increases in the lung tissue of MCT-treated rats, we examined the effect of WEB 2170, a specific PAF-antagonist, on lung in-flammatory responses and subsequent pulmonary hypertension induced by MCT. Treatment with WEB 2170 significantly reduced pulmonary hypertension and right ventricular hypertrophy at 3 weeks after MCT-injection. The eicosanoid levels in the lung tissue and the number of abnormal alveolar macrophages increased in MCT-treated rats at 3 weeks. In WEB 2170-treated MCT rats, the lung 6-keto prostaglandin F1αlevels and the number of abnormal alveolar macrophages were significantly lower than those of MCT-treated rats.Theae results indicate that the PAF-antagonist inhibits the development of pulmonary hypertension induced by MCT, and suggest a role for PAF in the lung inflammatory process that contributes to the development of pulmonary hypertension of MCT-treated rats.
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