Reduction of nitric oxide producing activity associated with in vitro aging in cultured human umbilical vein endothelial cell.
To investigate the involvement of nitric oxide (NO) in the pathogenesis of the cardiovascular system with aging, we studied the basal release of NO in cultured endothelial cells isolated from normal human umbilical veins (HUVECs) at different population doubling levels (PDLs). The release of NO was assayed by a newly established, highly sensitive assay system monitoring guanosine 3':5'-cyclic monophosphate (cGMP) formation in a pig kidney epithelial cell line cocultured with HUVECs. The cGMP formation by NO released from HUVECs decreased 3.3-fold between PDLs 8 (14.1 pmol/ml) and 50 (4.3 pmol/ml) (P < 0.01). The result suggests that the vaso-constrictive activity of endothelial cells increases during in vitro aging which may reflect the increased vascular disorders in aged people.