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 com pounds in vascular endothelial cells (ECs). Therefore, knowledge of how flo w affects the concentration of ATP and ADP at the EC surface may be importa nt for understanding shear stress-mediated vasoregulation. The concentratio n of ATP and ADP is determined by convective and diffusive transport as wel l as by hydrolysis of these nucleotides by ectonucleotidases at the EC surf ace. Previous mathematical modeling has demonstrated that for steady flow i n a parallel plate flow chamber, the combined ATP+ADP concentration does no t change considerably over a wide range of shear stress. This finding has b een used to argue that the effect of flow on adenine nucleotide transport c ould not account for the dependence of endothelial responses to ATP on the magnitude of applied shear stress. The present study extends the previous m odeling to include pulsatile flow as well as flow-induced endothelial ATP r elease. Our results demonstrate that flow-induced ATP release has a pronoun ced 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 similar to 10% over the wall shear stress range 0.1-10 dyne cm(-2), inclusion of this release leads to a concentration change of similar to 34%-106% over the same shear stress range, depending on how ATP release is modeled. These results sugges t that the dependence of various endothelial responses to shear stress on t he magnitude of the applied shear stress may be partially attributable to f low-induced changes in cell-surface adenine nucleotide concentration. (C) 2 001 Biomedical Engineering Society.