Modulation of ATP/ADP concentration at the endothelial surface by shear stress: effect of flow disturbance

Abstract

The adenine nucleotides ATP and ADP modulate the release of endothelial-derived relaxing factors and hence play an important role in flow-mediated arterial vasoregulation. Adenine nucleotide concentration at the endothelial cell (EC) surface within an artery is determined by a balance of convective-diffusive delivery of blood-borne nucleotides to the EC surface, hydrolysis of these nucleotides at the cell surface, and flow-induced ATP release from ECs. Previous numerical simulations in a parallel plate flow chamber had demonstrated that flow-induced ATP release has a profound effect on nucleotide concentration under both steady and pulsatile flow conditions. In the present study, we have extended this analysis to probe the impact of disturbed flow downstream of a backward facing step on adenine nucleotide concentration at the EC surface. The results have demonstrated that over a wide range of applied wall shear stress, the ATP concentration at the EC surface drops abruptly within the disturbed flow zone due to increased nucleotide residence time within this region. The concentration is intricately sensitive to the kinetics of flow-induced ATP release, and this sensitivity is more pronounced at lower levels of wall shear stress.