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Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor

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Abstract

Endothelium-derived relaxing factor (EDRF) is a labile humoral agent which mediates the action of some vasodilators. Nitrovasodi-lators, which may act by releasing nitric oxide (NO), mimic the effect of EDRF and it has recently been suggested by Furchgott1 that EDRF may be NO. We have examined this suggestion by studying the release of EDRF and NO from endothelial cells in culture. NO was determined as the chemiluminescent product of its reaction with ozone2. The biological activity of EDRF and of NO was measured by bioassay3. The relaxation of the bioassay tissues induced by EDRF was indistinguishable from that induced by NO. Both substances were equally unstable. Bradykinin caused concentration-dependent release of NO from the cells in amounts sufficient to account for the biological activity of EDRF. The relaxations induced by EDRF and NO were inhibited by haemoglobin and enhanced by superoxide dismutase to a similar degree. Thus NO released from endothelial cells is indistinguishable from EDRF in terms of biological activity, stability, and susceptibility to an inhibitor and to a potentiator. We suggest that EDRF and NO are identical.

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References

  1. 1. Furchgott, R. F. in Mechanisms of Vasodilatation Vol. IV (ed. Vanhoutte, P. M.) (Raven, New York, in the press). 2. Downes, M. J., Edwards, M. W., Elsey, T. S. & Walters, C. L. Analyst 101, 742–748 (1976). 3. Gryglewski, R. J., Moncada, S. & Palmer, R. M. J. Br. J. Pharmac 87, 685–694 (1986). 4. Griffith, T. M., Edwards, D. H., Lewis, M. J., Newby, A. C. & Henderson, A. H. Nature 308, 645–647 (1984). 5. Forstermann, U., Trogisch, G. & Busse, R. Eur. J. Pharmac. 106, 639–643 (1985). 6. Cocks, T. M. & Angus, J. A. in Vascular Neuroeffector Mechanisms (eds Bevan, J. A., Godfraind, T., Maxwell, R. A., Stoclet, J. C. & Worcel, M.) 131–136 (Elsevier, Amsterdam, 1985). 7. Martin, W., Villani, G. M., Jothianandan, D. & Furchgott, R. F. / Pharmac. exp. Ther. 232, 708–716 (1985). 8. Gibson, Q. H & Roughton, F. J. W. J. Physiol., Lond. 136, 507–526 (1957). 9. Gryglewski, R. J., Palmer, R. M. J. & Moncada, S. Nature 320, 454–456 (1986). 10. Rubanyi, G. M & Vanhoutte, P. M. Am. J. Physiol. 250, H222–H227 (1986). 11. Dale, H. H. Hull. Johns Hopkins Hosp. 53, 297–347 (1933). 12. Moncada, S., Palmer, R. M. J. & Gryglewski, R. J. Proc. natn. Acad. Sci. U.S.A. 83,9164–9168 (1986). 13. Blough, N. V. & Zafiriou, O. C. Inorg. Chem. 24, 3502–3504 (1985).

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  1. S. Moncada: To whom correspondence should be addressed.

Authors and Affiliations

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

    R. M. J. Palmer, A. G. Ferrige & S. Moncada

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  1. R. M. J. Palmer
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  2. A. G. Ferrige
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  3. S. Moncada
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Palmer, R., Ferrige, A. & Moncada, S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327, 524–526 (1987). https://doi.org/10.1038/327524a0

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  • DOI: https://doi.org/10.1038/327524a0

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