Pulmonary hypertension (PH) is associated with profound vascular remodeling and alterations in Ca2+ homeostasis in puhnonary arterial smooth muscle cells(PASMCs).Elevated [Ca2-]i in PASMCs of chronic hypoxia-and monocrotaline (MCT)-induced PH rats, and idiopathic PH patients, has been demonstrated through up-regulation of store-operated Ca2+ channels (SOCCs) which is encoded by the transient receptor potential (TRP) channel protein.STIM(stromal interaction nolecules)-Orai-TRPC pathway is thought to be involved in the regulation of Ca2+ homeostasis and pathogenesis of PH.Here we sought to examine the alterations in the expression of these molecular constituents of this signalling pathway in the PASMCs of MCT-induced PH rats.Rats developed severe PH and right ventrieular hypertrophy within three weeks after a single injection of MCT.Quantitative RTPCR found that there was a significant increase in the expression of STIM2, Orail/Orai2, TRPC1/TRPC4, whereas the expression of STIM1, Orai3 and TRPC6 was unchanged.Western blot confirned the upregulation of STIM2,Orail/Orai2 and TRPC1/TRPC4 protein.The time course of increase in the mRNA expression of STIM2, Orail and TRPC1 matched that of the increase in SOCE induced PAs(pulmonary arteries) contraction and mRVP(mean right ventricular pressure).Furthermore, correlation analysis showed STIM2-Orai2-TRPC1 are strongly related with SOCE induced PAs contraction.These results suggest that multiple components of Ca2+ signalling pathways are altered during PH and contribute synergistically to the enhanced SOCE in PASMCs.