Modulation of ATP/ADP concentration at the endothelial surface by shear stress: effect of flow-induced ATP release.

The adenine nucleotides ATP and ADP induce the production of vasoactive compounds in vascular endothelial cells (ECs). Therefore, knowledge of how flow affects the concentration of ATP and ADP at the EC surface may be important for understanding shear stress-mediated vasoregulation. The concentration of ATP and ADP is determined by convective and diffusive transport as well as by hydrolysis of these nucleotides by ectonucleotidases at the EC surface. Previous mathematical modeling has demonstrated that for steady flow in a parallel plate flow chamber, the combined ATP+ADP concentration does not change considerably over a wide range of shear stress. This finding has been used to argue that the effect of flow on adenine nucleotide transport could not account for the dependence of endothelial responses to ATP on the magnitude of applied shear stress. The present study extends the previous modeling to include pulsatile flow as well as flow-induced endothelial ATP release. Our results demonstrate that flow-induced ATP release has a pronounced effect on nucleotide concentration under both steady and pulsatile flow conditions. While the combined ATP+ADP concentration at the EC surface in the absence of flow-induced ATP release changes by only approximately 10% over the wall shear stress range 0.1-10 dyne cm(-2), inclusion of this release leads to a concentration change of approximately 34%-106% over the same shear stress range, depending on how ATP release is modeled. These results suggest that the dependence of various endothelial responses to shear stress on the magnitude of the applied shear stress may be partially attributable to flow-induced changes in cell-surface adenine nucleotide concentration.