Aim To testify that nitric oxide(NO)/ cGMP-dependent protein kinase(PKG) can regulate expression of inositol 1,4,5-trisphosphate receptor type Ⅰ(IP3RⅠ) and further adjust intracellular Ca²⁺ level in vascular smooth muscle cells(VSMC). Methods Colorimetric Assay(MTT assay) was used for cellular growth.Fluorescence measurements of [Ca²⁺]i were performed using a laserscanning confocal microscope.IP3RI expression was determined by using reverse transcripase-polymerase chain reaction(RT-PCR) and immunoblotting methods. Results Proliferative response of VSMC was inhibited by S-nitroso-N-acetylpenicillamine(SNAP) and Sp8-pCPT-cGMP and promoted by Rp-8-pCPT-cGMP.After VSMC were pretreated with Verapamil,cell proliferation was further inhibited by SNAP and Sp-8pCPT-cGMP respectively.Verapamil inhibited phenylephrine(PE)-stimulated intracellular Ca²⁺ variations,which could be further inhibited by SNAP and Sp-8pCPT-cGMP respectively and slightly promoted by Rp-8-pCPT-cGMP.IP3R Ⅰ mRNA expression levels were decreased by SNAP and Sp-8-pCPT-cGMP,and increased by Rp-8-pCPT-cGMP.Protein levels of IP3R Ⅰ paralleled the changes in mRNA levels in response to preceding stimulus factors. Conclusion NO/PKG can suppress IP3R Ⅰ expression at the transcriptional and translational level,and further modulate intracellular Ca²⁺ concentrations in VSMC.