Background: 

Pulmonary hypertension (PH) is characterized by high pulmonary blood pressure, vascular remodeling, and right ventricular hypertrophy. Suggest that one of pathogenesis factor of PH is the increase in plasma serotonin concentration. But the pathogenesis of PH is not fully understood and the treatment of PH is still unresolved.

Objective: 

The purpose of this study was to investigate whether inhibition of 5- HT transporter by fluoxetine would prevent the development of monocrotaline (MCT)-induced PH in rats.

Methods: 

Daily supplementation with fluoxetine (10 mg/kg/day for 3 weeks) or vehicle was started 7 days after to a single-dose injection of MCT (60 mg/kg). On day 28, dose- dependent change of the reactivity of isolated pulmonary vessels, right ventricular hypertrophy, and medial wall thickness were assessed.

Results: 

In rats that received daily supplementation of fluoxetine, vasoconstrictive response of pulmonary vessels with respect to serotonin was significantly reduced (7.22.9 vs. 20.23.1). Medial wall thickness (24.031.35 vs. 36.081.52) of pulmonary vessels and right ventricular hypertrophy (33.01.7 vs. 36.21.2) of fluoxetine-treated rats were less severe in rats with MCT-induced PH.

Conclusions: 

We conclude that daily supplementation of fluoxetine potently attenuates MCT-induced PH, right ventricular hypertrophy, and vascular remodeling in rats. The results suggest that the chronic administration of fluoxetine can restore the reactivity of pulmonary vessels and eliminate the symptoms of PH.