<正> Aim:To examine the time-and dose-dependent effects of ouabain on humanumbilical vein endothelial cells（HUVEC）in vivo,and the changes in aortic endot-helium and the different expression levels of Kv4.2 in vitro.Methods:The prolif-eration of HUVEC and cell death were determined by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyl-2H-tetrazolium bromide（MTT）assay,the incorporation of[3H]TdR,trypan blue staining,and lactate dehydrogenase（LDH）release.The response ofendothelial cells to ouabain was explored with a complementary DNA microarrayand a candidate gene was found."Ouabain-sensitive"hypertensive rats wereestablished by chronic administration of ouabain.Changes in the aortic endothe-lium were observed by electron microscopy,and the expression level of Kv4.2 indifferent animals was studied by using real-time quantitative reverse transcrip-tion-polymerase chain reaction（RT-PCR）.Results:Ouabain stimulated the prolif-eration of HUVEC at physiological concentrations（0.3-0.9 nmol/L）.Ouabain atpathological concentrations（0.9-1.8 nmol/L）inhibited proliferation and inducedcell death,mRNA profile analysis indicated that 340 genes were differentiallyexpressed after ouabain treatment:145 were upregulated,of which 6 wereupregulated significantly,including KCND2（encoding the potassium voltage-gated channel shal-related subfamily member 2）.The upregulated genes weremainly related to cell metabolism and transcription.In ouabain-sensitive hyper-tensive rats,the aortic endothelium was damaged and Kv4.2（coded by KCND2）was over-expressed.Conclusion:The physiological role of ouabain in HUVECmight involve the control of growth and metabolism.Ouabain at pathologicalconcentrations might affect the structure and function of the vascular endothe-lium by modification of expression of the KCND2 gene,and participate vascularremodeling in hypertension.
