Abstract
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 ∼ 10% over the wall shear stress range 0.1-10 dyne/cm -2, inclusion of this release leads to a concentration change of ∼ 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. © 2001 Biomedical Engineering Society.
PAC01: 8716Ac, 8716Uv, 8719Uv, 8715Vv, 8710+e
Similar content being viewed by others
References
Barakat, A. I.Responsiveness of vascular endothelium to shear stress: Potential role of ion channels and cellular cytoskeleton. Int. J. Mol. Med.4:323–332, 1999.
Barakat, A. I., E. V. M. Clark, P. A. Pappone, and P. F. Davies. A flow-activated chloride-selective current in vascular endothelial cells. Circ. Res.85:820–828, 1999.
Bodin, P., and G. Burnstock. ATP-stimulated release of ATP by human endothelial cells. J. Cardiovasc. Pharmacol.27:872–875, 1996.
Burnstock, G., and C. Kennedy. A dual function for adenosine 5′-triphosphate in the regulation of vascular tone. Circ. Res.58:319–330, 1986.
Chappell, D. C., S. E. Varner, R. M. Nerem, R. M. Medford, and R. W. Alexander. Oscillatory shear stress stimulates adhesion molecule expression in cultured human endothelium. Circ. Res.82:532–539, 1998.
Cusack, N. J., J. D. Pearson, and J. L. Gordon. Stereoselectivity of ectonucleotidases on vascular endothelial cells. Biochem. J.214:975–981, 1983.
Davies, P. F.Flow-mediated endothelial mechanotransduction. Physiol. Rev.75:519–560, 1995.
Dewey, Jr., C. F., S. R. Bussolari, M. A. Gimbrone, Jr., and P. F. Davies. The dynamic response of vascular endothelial cells to fluid shear stress. J. Biomech. Eng.103:177–188, 1981.
Dull, R. O., and P. F. Davies. Flow modulation of agonist (ATP)-response (Ca2+) coupling in vascular endothelial cells. Am. J. Physiol.261:H149–H156, 1991.
Furchgott, R. F.The role of endothelium in the response of vascular smooth muscle to drugs. Annu. Rev. Pharmacol. Toxicol.24:175–197, 1984.
Gudi, S., J. P. Nolan, and J. A. Frangos. Modulation of GTPase activity of G proteins by fluid shear stress and phospholipid composition. Proc. Natl. Acad. Sci. U.S.A.95:2515–2519, 1998.
Helmlinger, G., B. C. Berk, and R. M. Nerem. Calcium responses of endothelial cell monolayers subjected to pulsatile and steady laminar flow differ. Am. J. Physiol.269:C367–C375, 1995.
Helmlinger, G., R. V. Geiger, S. Schreck, and R. M. Nerem. Effects of pulsatile flow on cultured vascular endothelial cell morphology. J. Biomech. Eng.113:123–134, 1991.
Langille, B. L., and F. O'Donnell. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science231:405–407, 1986.
Lum, R. M., L. M. Wiley, and A. I. Barakat. Influence of different forms of shear stress on vascular endothelial TGF-β1 mRNA expression. Int. J. Mol. Med.5:635–641, 2000.
Milner, P., K. A. Kirkpatrick, V. Ralevic, V. Toothill, J. S. Pearson, and G. Burnstock. Endothelial cells cultured from human umbilical vein release ATP, substance P, and acetylcholine in response to increased flow. Proc. R. Soc. London, Ser. B Biol. Sci.241:245–248, 1990.
Mo, M., S. G. Eskin, and W. P. Schilling. Flow-induced changes in calcium signalling of vascular endothelial cells: Effects of shear stress and ATP. Am. J. Physiol.260:H1698–H1707, 1991.
Nerem, R. M.Vascular fluid mechanics, the arterial wall, and atherosclerosis. J. Biomech. Eng.114:274–282, 1992.
Nollert, M. U., and L. V. McIntire. Convective mass transfer effects on the intracellular calcium response of endothelial cells. J. Biomech. Eng.114:321–326, 1992.
Nollert, M. U., S. L. Diamond, and L. V. McIntire. Hydrodynamic shear stress and mass transport modulation of endothelial cell metabolism. Biotechnol. Bioeng.38:588–602, 1991.
Olesen, S. P., D. E. Clapham, and P. F. Davies. Hemodynamic shear stress activates a K+ current in vascular endothelial cells. Nature (London)331:168–170, 1988.
Olsson, R. A., and J. D. Pearson. Cardiovascular purinoceptors. Physiol. Rev.70:761–845, 1990.
Pearson, J. D., and J. L. Gordon. Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides. Nature (London)281:384–396, 1979.
Pirotton, S., E. Raspe, D. Demolle, C. Erneux, and J. Boeynaems. Involvement of inositol 1,4,5–triphosphate and calcium in the action of adenine nucleotides on aortic endothelial cells. J. Biol. Chem.262:17461–17466, 1987.
Pohl, U., J. Holtz, R. Busse, and E. Bassenge. Crucial role ofendothelium in the vasodilator response to increased flow in vivo. Hypertension8:37–47, 1986.
Resnick, N., and M. A. Gimbrone, Jr. Hemodynamic forces are complex regulators of endothelial gene expression. FASEB J.9:874–882, 1995.
Rubanyi, G. M., J. C. Romero, and P. M. Vanhoutte. Flow-induced release of endothelium-derived relaxing factor. Am. J. Physiol.250:H1145–H1149, 1986.
Shen, J., F. W. Luscinskas, A. Connolly, C. F. Dewey, Jr., and M. A. Gimbrone, Jr. Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells. Am. J. Physiol.262:C384–C390, 1992.
Shen, J., M. A. Gimbrone, Jr., F. W. Luscinskas, and C. F. Dewey, Jr. Regulation of adenine nucleotide concentration at endothelium-fluid interface by viscous shear flow. Biophys. J.64:1323–1330, 1993.
Suvatne, J., A. I. Barakat, and M. E. O'Donnell. Flow-induced expression of Na-K-Cl cotransport: Dependence on K+ and Cl− channels. Am. J. Physiol.280:C216–C227, 2001.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
John, K., Barakat, A.I. Modulation of ATP/ADP Concentration at the Endothelial Surface by Shear Stress: Effect of Flow-Induced ATP Release. Annals of Biomedical Engineering 29, 740–751 (2001). https://doi.org/10.1114/1.1397792
Issue Date:
DOI: https://doi.org/10.1114/1.1397792