TY - JOUR AU - Chen Xiao-niao AU - Xu Jun AU - Feng Zhe AU - Fan Ming AU - Han Jing-yao AU - Yang Zhuo PY - 2016 TI - Simvastatin combined with nifedipine enhances endothelial cell protection by inhibiting ROS generation and activating Akt phosphorylation JF - Acta Pharmacologica Sinica; Vol 31, No 7 (July 2010): Acta Pharmacologica Sinica Y2 - 2016 KW - N2 - Aim: To investigate the protective effects of simvastatin (Sim) combined with nifedipine (Nif) on endothelial cells and elucidate the action mechanism. Methods: Human umbilical vein endothelial cells (HUVEC) were used. mRNA and protein levels were measured by using reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively. Intracellular calcium and reactive oxygen species (ROS) were detected using confocal microscopy. The Griess assay was used to evaluate nitric oxide (NO) release. Results: Treatment of HUVEC with H 2 O 2 100 μmol/L for 30 min inhibited the mRNA and protein expression of endothelial nitric oxide synthase (eNOS). With increased concentrations of Nif, eNOS mRNA and protein levels increased (P 0.05). Compared with individual drug treatment, Akt phosphorylation and the ratio of p-eNOS/eNOS were up-regulated in the combination group, and this effect was inhibited by the phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002. Conclusion: The Sim-Nif combination effectively protects HUVEC against H 2 O 2 injury by inhibiting intracellular ROS generation, increasing the ratio of p-eNOS/eNOS and up-regulating Akt phosphorylation. UR - http://www.chinaphar.com/article/view/6724