NITRIC-OXIDE SYNTHESIS BY CULTURED ENDOTHELIAL-CELLS IS MODULATED BY FLOW CONDITIONS

In the present study, we examined the hypothesis that dynamic characte ristics of flow modulate the production of vasoactive mediators, namel y nitric oxide (NO) and endothelin-1. (ET-1), by human umbilical vein endothelial cells (HUVECs). Cells were exposed for 6 hours in a cone-a nd-plate apparatus to different types of flow: steady laminar, with sh ear stresses of 2, 8, and 12 dyne/cm(2); pulsatile laminar, with shear stress from 8.2 to 16.6 dyne/cm(2) and a frequency of 2 Hz; periodic laminar, with square wave cycles of lj minutes and shear stress from 2 to 8 dyne/cm(2); and turbulent, with shear stress of 8 dyne/cm(2) on average. A second culture dish was kept in a normal incubator as a sta tic control for each experiment. Laminar flow induced synthesis of NO by HUVECs that was dependent on shear-stress magnitude. Laminar shear stress at 8 dyne/cm(2) also upregulated the level of NO synthase mRNA. As observed with steady laminar flow, pulsatile flow also induced an increase in NO release by endothelial cells. When HUVECs were subjecte d to step-change increases of laminar shear, a further increase of NO synthesis was observed, compared with steady laminar shear of the same magnitude. Turbulent flow did not upregulate NO synthase mRNA or incr ease NO release. Both laminar and turbulent shear stress reduced, alth ough not significantly, ET-I mRNA and ET-1 production compared with th e static condition. These results indicate that local brood flow condi tions modulate the production of vasoactive substances by endothelial cells. This may affect vascular cell functions such as nonthrombogenic ity, regulation of blood flow, and vascular tone.