Role of peptide leukotrienes in monocrotaline-induced lung disease

Monocrotaline (MCT) causes lung inflammation and right ventricular hypertrophy associated with lung vascular thickening in rats. We hypothesized that peptide leukotrienes play a role in MCT-induced lung disease, and examined the effect of ONO 1078, a specific antagonist of LTC4, D4 and E4 receptors on MCT-induced right ventricular hypertrophy and on lung vascular thickening. Next, we measured leukotriene C4 (LTC4) levels in the lung tissue of MCT-treated rats. Within 3 weeks after the injection MCT had caused an increase in the ratio of right ventricular weight to left ventricle + septum weight (RV/(LV + S)) and an increase in media wall thickness of the muscular arteries of the lung. In rats given both ONO 1078 and MCT, these changes were significantly less severe than in rats given MCT only. The LTC4 levels in MCT-treated rats were significantly higher than in saline-treated control rats. These results indicate that this antagonist of peptide leukotriene receptors inhibits right ventricular hypertrophy induced by MCT, and suggest a role for peptide leukotrienes in the inflammatory process that contributes to lung vascular remodeling in MCT-treated rats.