Abstract
The role of leukocytes (WBCs) and platelets (PLTs) in the pulmonary circulation may be important in the development of monocrotaline (MCT)-induced pulmonary hypertension in rats. We investigated the suppressive effects of long-term prostaglandin E<sub>1</sub> (PGE<sub>1</sub>) aerosol on the changes in WBCs and PLTs in the peripheral blood and the pulmonary microvasculature during the development of chronic pulmonary hypertension in MCT rats by real-time confocal scanning laser microscopy. The number of WBCs and PLTs in peripheral blood did not significantly change by inhalation of PGE<sub>1</sub>. The number of WBCs and PLTs sequestered in the pulmonary microvasculature of rats subjected PGE<sub>1</sub> inhalation immediately after MCT injection rats with (MCT plus PGE<sub>1</sub> inhalation) significantly decreased from 1 to 4 weeks compared to rats not subjected to PGE<sub>1</sub> inhalation (p < 0.01). The pulmonary systolic arterial pressure and the weight ratio of the right ventricle to the intraventricular septum plus the left ventricle (RV/IVS + LV weight ratio or RV weight ratio) in rats with MCT plus PGE<sub>1</sub> inhalation significantly decreased compared to rats not subjected to PGE<sub>1</sub> inhalation (p < 0.01). The levels of peripheral CD62L-positive WBCs in rats with MCT plus PGE<sub>1</sub> inhalation significantly decreased from 1 to 2 weeks compared to rats not subjected to PGE<sub>1</sub> inhalation, but the levels of peripheral CD18 and CD49d-positive WBCs did not significantly change. We conclude that long-term inhalation of PGE<sub>1</sub> is a very useful therapy in chronic pulmonary hypertension, and the mechanism of suppressing pulmonary hypertension is associated with suppressive effects on sequestered WBCs, especially CD62-positive WBCs and PLTs in the pulmonary microvasculature.
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