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 the cerebral vasculature. Although the response of NO levels to shear stress has been investigated in various models using systemic endothelium, no study has evaluated human cerebral endothelial cells (HCE). We determined the NO levels of HCE cultured in an artificial capillary system in response to changes in shear stress. With direct measurement by a porphyrinic microsensor, we found that NO levels increased immediately with a peak at 7 h after changes in shear stress, and by 24 h dropped to a constant elevated baseline. Shear stress-mediated increases in NO levels were confirmed by the measurement of citrulline, an indirect measure of NO. Furthermore, NO levels by HCE were shown to decrease with decreasing shear stress levels. This study presents a novel system to study NO production by microvascular HCE, and indicates a linear relationship between shear stress and NO levels. As cerebral vessels age and lose transmural compliance, shear stress-mediated production of NO may play a greater role in cerebrovascular function and dysfunction.