Aliskiren attenuates the effects of interleukin-6 on endothelial nitric oxide synthase and caveolin-1 in human aortic endothelial cells.

Renin inhibitors enhance endothelial nitric oxide synthase (eNOS) bioavailability and have protective effects on endothelial function and atherosclerotic changes. This study was designed to investigate whether aliskiren attenuates the effects of interleukin-6 (IL-6) on eNOS and the eNOS-caveolin-1 interaction in human aortic endothelial cells (HAECs). In this study, we examined the effects of pretreatment with aliskiren on the changes of IL-6-induced expression and activation of eNOS and caveolin-1 in cultured HAECs. IL-6 inhibited and aliskiren increased the phosphorylation of eNOS at Ser1177; however, eNOS protein and mRNA expression were not changed. Pretreatment with aliskiren attenuated the inhibitory effects of IL-6 on eNOS phosphorylation and nitric oxide production. IL-6 increased the phosphorylation of caveolin-1 at Tyr14 without affecting the caveolin-1 protein and mRNA expression. Pretreatment with aliskiren attenuated the effects of IL-6 on caveolin-1 phosphorylation. The binding of eNOS and caveolin-1, as determined by a co-immunoprecipitation assay, was increased by IL-6 treatment and decreased by aliskiren pretreatment. Furthermore, treatment with short interfering RNA of the extracellular signal-regulated kinase gene reversed the effects of IL-6 and aliskiren on eNOS and caveolin-1. In conclusion, aliskiren attenuates the inhibitory effects of IL-6 on eNOS phosphorylation and nitric oxide production and IL-6 induced caveolin-1 phosphorylation. In addition, aliskiren reverses the effects of IL-6 on the eNOS-caveolin-1 interaction.