dv-7028 and Hypertension--Pulmonary

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.

Topics: Animals; Blood Platelets; Disease Models, Animal; Hypertension, Pulmonary; In Vitro Techniques; Lung; Male; Monocrotaline; Piperidines; Rats; Rats, Sprague-Dawley; Serotonin; Serotonin Antagonists; Triazines; Vasoconstriction

The aim was to clarify the role of serotonin (5-hydroxytryptamine, 5-HT) in monocrotaline induced pulmonary hypertension.. 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.. 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 x d-1) attenuated the increase in pulmonary arterial pressure, right ventricular hypertrophy, and medial thickening of the pulmonary arteries.. The present study suggests that 5-HT released from platelets contributes to the initiation and progression of monocrotaline induced pulmonary hypertension.

Topics: Animals; Blood Platelets; Culture Techniques; Hypertension, Pulmonary; Lung; Male; Monocrotaline; Piperidines; Platelet Count; Pulmonary Artery; Rats; Serotonin; Serotonin Antagonists; Triazines