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. 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 of endothelial cells to ouabain was explored with a complementary DNA microarray and a candidate gene was found. “” Ouabain-sensitive "hypertensive rats wereestablished by chronic administration of ouabain. Hearts 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 transcript-polymerase-polymerase chain reaction (RT-PCR). Results: Ouabain stimulated the prolif-eration of HUVEC at physiological concentrations (0.3-0.9 nmol / L) .Ouabain atpa The mRNA profile analysis indicated that 340 genes were differentially expressed after ouabain treatment: 145 were upregulated, of which 6 were highly regulated, including KCND2 (encoding the potassium voltage-gated channel shal -related subfamily member 2). The upregulated genes were mainly related to cell metabolism and transcription. ouabain-sensitive hyper-tensive rats, the aortic endothelium was damaged and Kv4.2 (coded by KCND2) was over-expressed. Conlusion: The physiological role of ouabain in the control of growth and metabolism. Ouabain at pathological conditions likely affect the structure and function of the vascular endotheli li by modification of expression of the KCND2 gene, and participate in vascular remodeling in hypertension.