Endothelial nitric oxide production and transport in flow chambers: The importance of convection.

Abstract

A computational model of Nitric Oxide (NO) production and transport within a parallel-plate flow chamber coated with endothelial cells is presented. The relationship between NO concentration and Wall Shear Stress (WSS) at the endothelium is investigated in detail. An increase in WSS is associated with two phenomena: enhanced NO production by the endothelial cells, and an increase in the velocity at which NO is convected out of the chamber. These two phenomena have opposite effects on endothelial NO concentration. In physiologically realistic cases, the balance between them is found to vary as WSS is raised, resulting in a complex non-monotonic dependence of endothelial NO concentration on WSS. Also, it is found that a NO concentration boundary layer develops within the chamber, leading to substantial spatial variations in NO concentration along the length of the device. Finally, the implications of a negative feedback mechanism (that affects NO production) are presented. The results emphasize the role of convection on NO transport within flow chambers, which has been overlooked or misinterpreted in most previous theoretical studies. It is hoped that the conclusions of this study can be used to aid accurate interpretation of related experimental data.