Role of serotonin in the progression of pulmonary hypertension

From 0.5 to 3 days after subcutaneous injection of monocrotaline (MCT) 60 mg/kg, prominent accumulation of platelets in the pulmonary capillaries accompanied with significant elevation of the plasma serotonin level was observed. To clarify the role of serotonin, the in vivo and in vitro effects of the selective 5-HT2 receptor antagonist, DV-7028, on MCT-induced pulmonary hypertension were studied. Oral administration of DV-7028 (10 mg/kg, twice daily) significantly suppressed the MCT-induced elevation of pulmonary arterial pressure, right ventricular hypertrophy and medial thickening of the muscular-type pulmonary arteries which occurred 23 days after MCT administration. The plasma level achieved by oral administration of 10 mg/kg DV-7028 was more than 10(-7) M. The hyperreactivity to serotonin in isolated pulmonary artery segments from MCT-treated rats was significantly reduced by DV-7028 (10(-7) M). The present study suggests that serotonin, released from platelets and accumulated in pulmonary capillaries, contributes to the initiation and/or progression of pulmonary hypertension in MCT-treated rats.