Objective To investigation on novel pharmacological target against pulmonary hypertension.It was recognized in the recent years that pulmonary hypertension(PHT)compromised of four components,i.e.vasoconstriction,hyperplasia,micro thrombosis and inflammation of pulmonary vasculature.Pulmonary vascular hyperplasia is a hallmark pathologic feature of pulmonary hypertension.Hyperplasia of rat pulmonary artery smooth muscle cells(PASMCs)was significantly increased,and PASMCs from rats or human beings with PHT grow faster than those from control subjects when stimulated by serotonin or serum.Pulmonary hypertension(PHT)is the major cause of right ventricular hypertrophy and eventually right heart failure.5-hydroxytraptamine(5-HT)as mitogen for vascular smooth muscle cells plays an important role in the development of PHT.It is known that selective serotonin re-uptake inhibitors(SSRIs)restrain 5-HT internalization.Therefore,this study was aimed to investigate if SSRIs may have protective effect against monocrotaline(MCT)-induced right ventricular hypertrophy.Methods induced chronic pulmonary hypertension in Wistar rats was established;fluoxetine and sertraline(2,10 mg·kg-1·d-1 were administered by gavages.3 w after MCT injection,right ventricular index(RVI),pulmonary artery pressure(PAP),heart and lung morphology were measured or investigated.5-HT transporter(SERT)assayed by RT-PCR or Western blot.Results MCT-Results RVI was significantly increased in MCT group(P<0.01 vs control)and reduced to by fluoxetine(10 mg·kg-1·d-1)and 0.42±0.04 by Sertraline(10 mg·kg-1·d-1)(both P<0.05 vs MCT).PAP increased significantly by MCT(P<0.01 vs control).Fluoxetine(10 mg·kg-1·d-1),or sertraline(10 mg·kg-1·d-1)attenuated MCT-induced increase of PAP,respectively(both P<0.05 vs MCT).MCT raised significantly Pulmonary artery muscularization(P<0.01 vs control),and attenuated by fluoxetine or sertraline(P<0.01 vs MCT).MCT increased SERT mRNA and protein expression,and both were significantly attenuated by fluoxetine or sertraline,respectively.Conclusions SSRIs protect against MCT-induced right ventricular hypertrophy,RVI,PAP,Pulmonary artery muscularization,which may be relevant to inhibition of SERT and the results suggest that SERT may be a novel pharmacological target against pulmonary hypertension. Objective To investigate the novel pharmacological target against pulmonary hypertension. It was recognized in the recent years that pulmonary hypertension (PHT) compromised of four components, ievasoconstriction, hyperplasia, microthrombosis and inflammation of pulmonary vasculature. Pulmonary vascular hyperplasia is a hallmark pathologic feature of pulmonary hypertension. Hyperplasia of rat pulmonary artery smooth muscle cells (PASMCs) was significantly increased, and PASMCs from rats or human beings with stimulated by serotonin or serum. Pulmonary hypertension (PHT) is the major cause of right ventricular hypertrophy and eventually right heart failure. 5-hydroxytraptamine (5-HT) as mitogen for vascular smooth muscle cells plays an important role in the development of PHT. It is known that selective serotonin re-uptake inhibitors (SSRIs) restrain 5-HT internalization.Therefore, this study was aimed to investigate if SSRIs may have protective effec t against monocrotaline (MCT) -induced right ventricular hypertrophy. Methods induced chronic pulmonary hypertension in Wistar rats was established; fluoxetine and sertraline (2,10 mg · kg-1 · d-1 were administered by gavages.3 w after MCT injection, right ventricular index (RVI), pulmonary artery pressure (PAP), heart and lung morphology were measured or investigated. 5-HT transporter (SERT) assayed by RT-PCR or Western blot. Results MCT-Results RVI was significantly increased in MCT group (P <0.01 vs control) and reduced to by fluoxetine (10 mg · kg -1 · d -1) and 0.42 ± 0.04 by Sertraline (10 mg · kg -1 · d -1) (both P <0.05 vs. MCT) .PAP increased significantly by MCT (P <0.01 vs control) .Fluoxetine (10 mg · kg -1 · d -1), or sertraline (10 mg · kg -1 · d -1) attenuated MCT-induced increase of PAP, (P <0.05 vs. MCT). MCT increased significantly Pulmonary artery muscularization (P <0.01 vs. control), and attenuated by fluoxetine or sertraline cantly attenuated by fluoxetine or sertraline, respectively. Conclusions SSRIs protect against MCT-induced right ventricular hypertrophy, RVI, PAP, Pulmonary artery muscularization, which may be relevant for inhibition of SERT and the results suggest that SERT may be a novel pharmacological target against pulmonary hypertension .