Estrogen increases inducible nitric oxide synthase gene expression

Objective: The goal of this study was to determine whether estrogen increases the expression of the inducible nitric oxide synthase gene. Study Design: An inducible nitric oxide synthase fusion gene was created with its promoter and the reporter gene, luciferase. COS cells were transfected transiently with the fusion gene and cotransfected with an estrogen receptor-α expression plasmid to ensure the presence of an estrogen receptor. Cells were then exposed to estradiol (1 nmol/L and 10 nmol/L) or a cytokine mix that consisting of tumor necrosis factor-α, interleukin-1β, and interferon gamma. Gene expression was measured in relative light units. Results: Estradiol increased the expression of inducible nitric oxide synthase by an average of 31.2% in the COS cells that were cotransfected with estrogen receptor compared with −10.4% in cells without estrogen receptor (P = .006). Conclusion: Inducible nitric oxide synthase expression was increased with the addition of estrogen. These data support previous studies that demonstrated the inflammatory effects of estrogen and provides further insight into the mechanism by which estrogen might have an impact on the cardiovascular system.