Suppressive effect of pulmonary hypertension and leukocyte activation by inhaled prostaglandin E1 in rats with monocrotaline-induced pulmonary hypertension

The effect of long-term prostaglandin E-1 (PGE(1)) aerosol was investigated in rats with chronic pulmonary hypertension induced by monocrotaline (MCT). Six-week-old Sprague-Dawley rats were separated into groups of 6 and administered 1 mL of saline (group A) or 60 mg/kg of MCT. The MCT-treated mice were then administered either nothing (group B) or 5 mL of PGE(1) (4 mug/mL) via a nebulizer every day for 1 week (group C), 2 weeks (group D), 3 weeks (group E), or 4 weeks (group F) after MCT injection. The pulmonary artery medial wall thickness was measured and the weight ratio of the right ventricle to the intraventricular septum plus the left ventricle (RV ratio) was determined 1 month after saline or MCT injection. Leukocytes positive for the activation markers CD18, CD49d, CD62L were determined in each group every week for 1 month. The pulmonary artery medial wall thickness and RV ratio gradually decreased in proportion to the duration of PGE(1) inhalation. In groups E and F, the level of CD62L-positive leukocytes gradually decreased after MCT injection in proportion to the duration of PGE(1) inhalation. We conclude that long-term inhalation of PGE(1) is very useful therapy in chronic pulmonary hypertension and that the anti-leukocyte effect of PGE(1) is associated with the suppression of CD62L-positive leukocytes at an early stage of progression.