ROLE OF 5-HYDROXYTRYPTAMINE IN THE PROGRESSION OF MONOCROTALINE-INDUCED PULMONARY-HYPERTENSION IN RATS

Objective: The aim was to clarify the role of serotonin (5-hydroxytryptamine, 5-HT) in monocrotaline induced pulmonary hypertension. Methods: Plasma 5-HT levels, pulmonary capillary platelet count, and vascular responsiveness to 5-HT were evaluated in the model. The effects of the selective 5-HT2 receptor antagonist, DV-7028, on the development of pulmonary hypertension were also investigated. Results: Plasma 5-HT was raised 12 h to 3 d after monocrotaline administration (60 mg.kg-1), coinciding with accumulation of platelets in the pulmonary circulation. Isolated pulmonary arteries showed hyperreactivity to 5-HT at 14 and 21 d after monocrotaline. Administration of DV-7028 (20 mg.kg-1.d-1) attenuated the increase in pulmonary arterial pressure, right ventricular hypertrophy, and medial thickening of the pulmonary arteries. Conclusions: The present study suggests that 5-HT released from platelets contributes to the initiation and progression of monocrotaline induced pulmonary hypertension.