Activation and up-regulation of nitric oxide synthase in human umbilical vein endothelial cells by polycyclic aromatic hydrocarbons

PAHs, including naphthalene, fluoranthene and fluorene rapidly induced extracellular Ca²⁺ influx and hence elevation of intracellular Ca²⁺ concentration and NO production. The effect can be inhibited by Ca²⁺ channel blocker but not by P450 inhibitor. In addition to the rapid effect, we have also found that the eNOS mRNA and protein expression were augmented in HUVECs treated with PAHs at concentration as low as 0.1 μM for 24 h. These effects were abolished when the HUVECs were pretreated with the BAPTA, NiCl₂ and SKF96365, as well as SKF525A. Our results revealed that, for the first time, PAHs induce the activation of eNOS and enhance eNOS protein expression in HUVECs both in a Ca²⁺-dependent manner.