• Jing Wu, Min-xiang Lei, Xiao-yun Xie, and Xiang-ling Feng.
• Department of Endocrinology, Xiangya Hospital, Central South University, Changsha 410008, China. wujing0731@hotmail.com
• Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2007 Oct 1; 32 (5): 824-30.

ObjectiveTo observe the effect of rosiglitazone on the production of nitric oxide (NO) and the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) /the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells(HUVECs), and to investigate the mechanism of signal transduction of rosiglitazone in improving the endothelial function.MethodsHUVECs were treated with various concentrations of rosiglitazone. The NO level was measured using Griess Reaction in cell culture supernatants; the expressions of PI3K-, PKB- and eNOS mRNA were measured using RT-PCR; and the expressions of PKB, eNOS, and phosphorylation of PKB-Ser473, eNOS-Ser1177 were measured using Western Blot.ResultsRosiglitazone increased the endothelial NO production in a dose- and time-dependent manner in cultured HUVECs, and also increased the expression of PI3K mRNA and the phosphorylation of PKB-Ser473 and eNOS-Ser1177 in a concentration-dependent manner, with no alteration in the expression of PKB and eNOS in cultured HUVECs. N(w)-nitro-L- arginine methyl ester (L-NAME, eNOS synthase inhibitor) blocked the rosiglitazone-induced NO formation; LY294002 (a PI3K inhibitor) prevented the NO production; and the phosphorylation of eNOS and PKB was induced by rosiglitazone.ConclusionTreatment with rosiglitazone can increase the NO production and improve the endothelial function through up-regulating the PI3K/PKB/eNOS signal pathways in cultured HUVECs.

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