Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor

Nature volume 320, pages 454–456 (1986)Cite this article

Abstract

Endothelium-derived vascular relaxing factor (EDRF)1 is a humoral agent that is released by vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine and bradykinin2. EDRF is very unstable, with a half-life of between 6 (refs 3, 4) and 50 (ref. 5) s, and is clearly distinguishable from prostacyclin6. The chemical structure of EDRF is unknown but it has been suggested that it is either a hydroperoxy- or free radical-derivative of arachidonic acid or an unstable aldehyde, ketone or lactone3. We have examined the role of superoxide anion (O2−) in the inactivation of EDRF released from vascular endothelial cells cultured on microcarrier beads and bioassayed using a cascade of superfused aortic smooth muscle strips7. With this system, we have now demonstrated that EDRF is protected from breakdown by superoxide dismutase (SOD) and Cu2+, but not by catalase, and is inactivated by Fe2+. These findings indicate that O2− contributes significantly to the instability of EDRF.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Furchgott, R. F. & Zawadzki, J. V. Nature 288, 373–376 (1980).

    Article  ADS  CAS  Google Scholar 

  2. Furchgott, R. F. A. Rev. Pharmac. Tox. 24, 175–197 (1984).

    Article  CAS  Google Scholar 

  3. Griffith, T. M., Edwards, D. H., Lewis, M. J., Newby, A. C. & Henderson, A. H. Nature 308, 645–647 (1984).

    Article  ADS  CAS  Google Scholar 

  4. Cocks, T. M., Angus, J. A., Campbell, J. H. & Campbell, G. R. J. cell. Physiol. 123, 310–320 (1985).

    Article  CAS  Google Scholar 

  5. Förstermann, U., Trogisch, G. & Busse, R. Eur. J. Pharmac. 106, 639–643 (1985).

    Article  Google Scholar 

  6. Moncada, S., Gryglewski, R. J., Bunting, S. & Vane, J. R. Nature 263, 663–665 (1976).

    Article  ADS  CAS  Google Scholar 

  7. Gryglewski, R. J., Moncada, S. & Palmer, R. M. J. Br. J. Pharmac. 87, 685–694 (1986).

    Article  CAS  Google Scholar 

  8. Vane, J. R. Br. J. Pharmac. Chemother. 23, 360–373 (1964).

    Article  CAS  Google Scholar 

  9. Rapaport, R. M., Drazin, M. B. & Murad, F. Nature 306, 174–176 (1983).

    Article  ADS  Google Scholar 

  10. Martin, W., Villani, G. M., Jothianandan, D. & Furchgott, R. F. J. Pharmac. exp. Ther. 232, 708–716 (1985).

    CAS  Google Scholar 

  11. Keele, B. B., McCord, J. M. & Fridovich, I. J. biol Chem. 246, 2875–2880 (1971).

    CAS  PubMed  Google Scholar 

  12. Heikkila, R. E. & Cohen, G. in Superoxide and Superoxide Dismutases (eds Michelson, A. M., McCord, J. M. & Fridovich, I.) 367–373 (Academic, London, 1977).

    Google Scholar 

  13. Block, E. R., Patel, J. M. & Sheridan, N. P. J. cell Physiol. 122, 240–248 (1985).

    Article  CAS  Google Scholar 

  14. Epel, B. L. & Neumann, J. Biochim. biophys. Acta. 325, 520–529 (1973).

    Article  CAS  Google Scholar 

  15. Lumsden, J. & Hall, D. C. Biochem. biophys. Res. Commun. 64, 595–602 (1975).

    Article  CAS  Google Scholar 

  16. Michelson, A. M. in Superoxide and Superoxide Dismutases (eds Michelson, A. M., McCord, J. M. & Fridovich, I.) 77–86 (Academic, London, 1977).

    Google Scholar 

  17. Freeman, B. A. & Crapo, J. D. Lab. Invest. 47, 412–426 (1982).

    CAS  PubMed  Google Scholar 

  18. Moncada, S., Gryglewski, R. J., Bunting, S. & Vane, J. R. Prostaglandins. 12, 715–733 (1976).

    Article  CAS  Google Scholar 

  19. Vanhoutte, P. M. & Rubanyi, G. M. Clin. Res. 33, 523A (1985).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wellcome Research Laboratories, Langley Court, Beckenham, Kent, BR3 3BS, UK

    R. J. Gryglewski, R. M. J. Palmer & S. Moncada

Authors
  1. R. J. Gryglewski
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. R. M. J. Palmer
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. S. Moncada
    View author publications

    You can also search for this author inPubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gryglewski, R., Palmer, R. & Moncada, S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320, 454–456 (1986). https://doi.org/10.1038/320454a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/320454a0

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing