Alteration of nitric oxide gas on gene expression of endothelin-1 and endothelial nitric oxide synthase by a time- and dose-dependent manner in human endothelial cells

Our purpose was to investigate the gene expression of endothelin-1 (ET-1) and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVECs) under various concentrations and periods of exogenous nitric oxide (NO) gas exposure. Cultured HUVECs were exposed to 0, 20, and 80 ppm NO for 0, 24, and 48 h. With NO exposure for 24 h, ET-1 peptide levels decreased in both the 20 and 80 ppm groups. Thereafter, at 48 h, ET-1 peptide levels persistently decreased in the 20 ppm group, but significantly increased in the 80 ppm group. Furthermore, there was a significant decrease in the expression levels of eNOS protein and mRNA in the 80 ppm 48 h group. The data suggest a time- and dose-dependent effect of NO gas exposure on the gene expression of ET-1 and eNOS in HUVECs. A high concentration and long period of NO exposure induces an inhibition of eNOS and enhancement of ET-1, which could lead to vasoconstriction. These findings may have clinical implications in NO therapy regarding the optimal dose and period.