Skip to main content
SpringerLink
Log in

Endothelial Nitric Oxide Production and Transport in Flow Chambers: The Importance of Convection

  • Published:
Annals of Biomedical Engineering Aims and scope Submit manuscript

Abstract

A computational model of Nitric Oxide (NO) production and transport within a parallel-plate flow chamber coated with endothelial cells is presented. The relationship between NO concentration and Wall Shear Stress (WSS) at the endothelium is investigated in detail. An increase in WSS is associated with two phenomena: enhanced NO production by the endothelial cells, and an increase in the velocity at which NO is convected out of the chamber. These two phenomena have opposite effects on endothelial NO concentration. In physiologically realistic cases, the balance between them is found to vary as WSS is raised, resulting in a complex non-monotonic dependence of endothelial NO concentration on WSS. Also, it is found that a NO concentration boundary layer develops within the chamber, leading to substantial spatial variations in NO concentration along the length of the device. Finally, the implications of a negative feedback mechanism (that affects NO production) are presented. The results emphasize the role of convection on NO transport within flow chambers, which has been overlooked or misinterpreted in most previous theoretical studies. It is hoped that the conclusions of this study can be used to aid accurate interpretation of related experimental data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8

Similar content being viewed by others

References

  1. Azarov, I., K. Huang, S. Basu, M. Gladwin, N. Hogg, and D. Kim-Shapiro. Nitric oxide scavenging by red blood cells as a function of hematocrit and oxygenation. J. Biol. Chem. 280(47):39,024–39,032, 2005.

    Article  CAS  Google Scholar 

  2. Butler, A., I. Megson, and P. Wright. Diffusion of nitric oxide and scavenging by blood in the vasculature. Biochim. Biophys. Acta (BBA) - General Subjects 1425(1):168–176, 1998.

    Article  CAS  Google Scholar 

  3. Caro, C., J. Fitz-Gerald, and R. Schroter. Arterial wall shear and distribution of early atheroma in man. Nature 223(5211):1159–1160, 1969.

    Article  CAS  PubMed  Google Scholar 

  4. Chen, K., R. Pittman, and A. Popel. Nitric oxide in the vasculature where does it come from and where does it go? A quantitative perspective. Antioxid. Redox Signal. 10(7):1185–1198, 2008.

    Article  CAS  PubMed  Google Scholar 

  5. Chen, K., and A. S. Popel. Theoretical analysis of biochemical pathways of nitric oxide release from vascular endothelial cells. Free Radic. Biol. Med. 41:668–680, 2006

    Article  CAS  PubMed  Google Scholar 

  6. Cheng, C., R. van Haperen, M. de Waard, L. van Damme, D. Tempel, L. Hanemaaijer, G. van Cappellen, J. Bos, C. Slager, D. Duncker, A. van der Steen, R. Crom, and R. Krams. Shear stress affects the intracellular distribution of enos: direct demonstration by a novel in vivo technique. Blood 106(12):3691–3698, 2005.

    Article  CAS  PubMed  Google Scholar 

  7. Cheng, C., D. Tempel, A. Oostlander, F. Helderman, F. Gijsen, J. Wentzel, R. van Haperen, D. Haitsma, P. Serruys, A. F. W. van der Steen, R. de Crom, and R. Krams. Rapamycin modulates the enos vs. shear stress relationship. Cardiovasc. Res. 78(1):123–129, 2008.

    Article  CAS  PubMed  Google Scholar 

  8. David, T. Wall shear stress modulation of atp/adp concentration at the endothelium. Ann. Biomed. Eng. 31(10):1231–1237, 2003.

    Article  Google Scholar 

  9. Diem, K., editor. Documenta Geigy, Scientzjic Tables. Geigy Pharmaceuticals, Div. of Geigy Chemicals Corp., 1962.

  10. Ethier, R. Computational modeling of mass transfer and links to atherosclerosis. Ann. Biomed. Eng. 30(4):461–471, 2002.

    Article  PubMed  Google Scholar 

  11. Fadel, A., K. Barbee, and D. Jaron. A computational model of nitric oxide production and transport in a parallel plate flow chamber. Ann. Biomed. Eng. 37(5):943–954, 2009.

    Article  CAS  PubMed  Google Scholar 

  12. Frangos, J., T. Huang, and C. Clark. Steady shear and step changes in shear stimulate endothelium via independent mechanism—superposition of transient and sustained nitric oxide production. Biochem. Biophys. Res. Commun. 224:660–665, 1996.

    Article  CAS  PubMed  Google Scholar 

  13. Grumbach, I., C. Wei, S. Mertens, and D. Harrison. A negative feedback mechanism involving nitric oxide and nuclear factor kappa-b modulates endothelial nitric oxide synthase transcription. J. Mol. Cell. Cardiol. 39(4):595–603, 2005.

    Article  CAS  PubMed  Google Scholar 

  14. Hakim, T., K. Sugimori, E. Camporesi, and G. Anderson. Half-life of nitric oxide in aqueous solutions with and without haemoglobin. Physiol. Meas. 17(4):267–277, 1996.

    Article  CAS  PubMed  Google Scholar 

  15. Kanai, A., H. Strauss, G. Truskey, A. Crews, S. Grunfeld, and T. Malinski. Shear stress induces atp-independent transient nitric oxide release from vascular endothelial cells, measured directly with a porphyrinic microsensor. Circ. Res. 77(2):284–293, 1995

    CAS  PubMed  Google Scholar 

  16. Kavdia, M., and A. Popel. Wall shear stress differentially affects no level in arterioles for volume expanders and hb-based O2 carriers. Microvasc. Res. 66(1):49–58, 2003.

    Article  CAS  PubMed  Google Scholar 

  17. Kelm, M. Nitric oxide metabolism and breakdown. Biochim. Biophys. Acta 1411:273–289, 1999.

    Google Scholar 

  18. Kharitonov, V., A. Sundquist, and V. Sharma. Kinetics of nitric oxide autoxidation in aqueous solution. J. Biol. Chem. 8(269):5881–5883, 1994.

    Google Scholar 

  19. Lewis, R., and W. Deen. Kinetics of the reaction of nitric oxide with oxygen in aqueous solutions. Chem. Res. Toxicol. 7(4):568–574, 2002.

    Article  Google Scholar 

  20. Loscalzo, J. Endothelium, nitric oxide, and atherosclerosis: from basic mechanisms to clinical implications. Circulation 102(8):e51, 2000.

    Google Scholar 

  21. Malek, A., S. Alper, and S. Izumo. Hemodynamic shear stress and its role in atherosclerosis. JAMA 282(21):2035–2042, 1999.

    Article  CAS  PubMed  Google Scholar 

  22. Malinski, T., Z. Taha, S. Grunfeld, S. Patton, M. Kaptruczak, and P. Tomboulian. Diffusion of nitric oxide in the aorta wall monitored in situ by porphyrinic microsensors. Biochem. Biophys. Res. Commun. 193:365–375, 1993.

    Google Scholar 

  23. Nagano, T. Practical methods for detection of nitric oxide. Luminescence 14(6):283–290, 1999.

    Article  CAS  PubMed  Google Scholar 

  24. Nakatsubo, N., H. Kojima, K. Kikuchi, H. Nagoshi, Y. Hirata, D. Maeda, Y. Imai, T. Irimura, and T. Nagano. Direct evidence of nitric oxide production from bovine aortic endothelial cells using new fluorescence indicators: diaminofluoresceins. FEBS Lett. 427(2):263–266, 1998.

    Article  CAS  PubMed  Google Scholar 

  25. Plank, M., D. Wall, and T. David. The role of endothelial calcium and nitric oxide in the localisation of atherosclerosis. Math. Biosci. 207(1):26–39, 2007.

    Article  CAS  PubMed  Google Scholar 

  26. Probstein, R. F. Physicochemical Hydrodynamics: An Introduction. JohnWiley and Sons Inc., 2003.

  27. Qiu, W., D. Kass, Q. Hu, and R. Ziegelstein. Determinants of shear stress-stimulated endothelial nitric oxide production assessed in real-time by 4,5-diaminofluorescein fluorescence. Biochem. Biophys. Res. Commun. 286(2):328–335, 2001.

    Article  CAS  PubMed  Google Scholar 

  28. Sherwin, S. J., and G. Karniakadis. Spectral/hp Element Methods for Computational Fluid Dynamics. Oxford University Press, 2005.

  29. Smith, K., L. Moore, and H. Layton. Advective transport of nitric oxide in a mathematical model of the afferent arteriole. Am. J. Physiol. Renal. Physiol. 284(5):1080–1096, 2003.

    Google Scholar 

  30. Vaughn, M. W., L. Kuo, and J. Liao. Effective diffusion distance of nitric oxide in the microcirculation. AJP Heart Circ. Physiol. 274:1705–1714, 1998.

    Google Scholar 

  31. White, C., and J. Frangos. The shear stress of it all: the cell membrane and mechanochemical transduction. Phil. Trans. R. Soc. B 362:1459–1467, 2007.

    Article  CAS  PubMed  Google Scholar 

  32. Wiesner, T., B. Berk, and R. Nerem. A mathematical model of the cytosolic-free calcium response in endothelial cells to fluid shear stress. Proc. Natl Acad. Sci. USA 94(8):3726–3731, 1997.

    Article  CAS  PubMed  Google Scholar 

  33. Wink, D., J. Darbyshire, R. Nims, J. Saavedra, and P. Ford. Reactions of the bioregulatory agent nitric oxide in oxygenated aqueous media: determination of the kinetics for oxidation and nitrosation by intermediates generated in the nitric oxide/oxygen reaction. Chem. Res. Toxicol. 6(1):23–27, 2002.

    Article  Google Scholar 

  34. Yamamoto, K., T. Sokabe, T. Matsumoto, K. Yoshimura, M. Shibata, N. Ohura, T. Fukuda, T. Sato, K. Sekine, S. Kato, M. Isshiki, T. Fujita, M. Kobayashi, K. Kawamura, H. Masuda, A. Kamiya, and J. Ando. Impaired flow-dependent control of vascular tone and remodeling in p2x4-deficient mice. Nat. Med. 12(1):133–137, 2006.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study is funded by Fundación Caja Madrid and the Engineering and Physical Sciences Research Council. The authors would like to thank Prof. Peter Weinberg and Dr. Peter Vincent for useful discussions throughout the development of this work, and the British Heart Foundation Research Excellence Centre for support.

Author information

Authors and Affiliations

  1. Department of Aeronautics, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK

    A. M. Plata & S. J. Sherwin

  2. Department of Bioengineering, Imperial College London, London, UK

    R. Krams

Authors
  1. A. M. Plata
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. J. Sherwin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Krams
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. J. Sherwin.

Additional information

Associate Editor Jennifer West oversaw the review of this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Plata, A.M., Sherwin, S.J. & Krams, R. Endothelial Nitric Oxide Production and Transport in Flow Chambers: The Importance of Convection. Ann Biomed Eng 38, 2805–2816 (2010). https://doi.org/10.1007/s10439-010-0039-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10439-010-0039-x

Keywords

Search

Navigation