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

Naturevolume 320pages454456 (1986) | Download Citation

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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.

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References

  1. 1

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

  2. 2

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

  3. 3

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

  4. 4

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

  5. 5

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

  6. 6

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

  7. 7

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

  8. 8

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

  9. 9

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

  10. 10

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

  11. 11

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

  12. 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).

  13. 13

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

  14. 14

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

  15. 15

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

  16. 16

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

  17. 17

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

  18. 18

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

  19. 19

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

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

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

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

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