726 NO release from vascular endothelial cells in response to wall shear stress

Abstract

The physiological and pathophysiological mechanisms linked to reactive oxygen and nitrogen species in arterial vessel and tissue are not well established because the predictions and results in the past were not in agreement. In order to address the role of nitric oxide and its downstream mechanism in the localization of atherosclerosis, the effects of mass transport and hemodynamics on endothelial cells functions were investigated. An experiment model that simulates in vivo spatial patterns of flow separation, recirculation, and reattachment have been developed to examine the release of nitric oxide from the endothelial cell layer in response to the shear stress with a complex spatial variation. Direct exposure of cells to 20dyne/cm^2 shear stress after the onset of flow induced a rapid elevation in the nitric oxide release in the first ten minutes followed by a less rapid production. A mathematical mass transport model was constructed in the geometry mimicking the experimental flow domain to follow coupled biochemical reactions and diffusion of oxygen, nitric oxide, superoxide, and peroxynitrite, around the recirculation region. Steady state mass transport in nitric oxide, oxygen partial pressure and the associated production of peroxynitrite were predicted. The mass transport model provides an objective way to evaluate the relative influence of mass transport and hemodynamics on biochemical pathways related to the initiation of atherosclerotic lesions.