Effects of shear stress on nitric oxide levels of human cerebral endothelial cells cultured in an artificial capillary system

Nitric oxide (NO) is an important vasodilator with various activities in th e cerebral vasculature. Although the response of NO levels to shear stress has been investigated in various models using systemic endothelium, no stud y has evaluated human cerebral endothelial cells (HCE). We determined the N O levels of HCE cultured in an artificial capillary system in response to c hanges in shear stress. With direct measurement by a porphyrinic microsenso r, we found that NO levels increased immediately with a peak at 7 h after c hanges in shear stress, and by 24 h dropped to a constant elevated baseline . Shear stress-mediated increases in NO levels were confirmed by the measur ement of citrulline, an indirect measure of NO. Furthermore, NO levels by H CE were shown to decrease with decreasing sheer stress levels. This study p resents a novel system to study NO production by microvascular HCE, and ind icates a Linear relationship between shear stress and NO levels, As cerebra l vessels age and lose transmural compliance, shear stress-mediated product ion of NO may play a greater role in cerebrovascular function and dysfuncti on. (C) 1999 Published by Elsevier Science B.V. All rights reserved.