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:

Aspirin causes short-lived inhibition of bradykinin-stimulated prostacyclin production in man

Abstract

Acetylsalicyclic acid (aspirin) inhibits prostanoid synthesis1,2 by irreversible acetylation of fatty acid cyclooxygenase (EC 1.14.99.1)3. It thereby inhibits synthesis of pro-aggregatory thromboxane A2 (TXA2) by platelets2,4 and is widely used in the treatment and prophylaxis of vascular disease. Its efficacy, however, may be reduced since it also inhibits formation of prostacyclin (PGI2)5,6 which is a vasodilator and anti-aggregatory agent7,8. There is uncertainty over the optimum dose regimen for aspirin since although it inhibits platelet thromboxane production for many days4, the magnitude and duration of its effect on PGI2 production by vascular endothelium in vivo is unknown. Resting plasma concentrations of PGI2 (measured as the stable hydrolysis product 6-oxo-PGF) are at or below the limit of sensitivity of the most sensitive assays9 and cannot therefore be used to demonstrate a reduction in production. Bradykinin stimulates PGI2 synthesis by cultured human vascular endothelial cells10 and we have shown that it stimulates PGI2 production by man in vivo11. We report here that an oral dose of aspirin (600 mg) causes rapid and substantial inhibition of bradykinin-stimulated PGI2 production, but recovery occurs within 6 hours; this implies that endothelial PGI2 synthesis would be spared most of the time during dosing once daily with even this relatively large dose of aspirin.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Similar content being viewed by others

References

  1. Ferreira, S. H., Moncada, S. & Vane, J. R. Nature new Biol. 231, 237–239 (1971).

    Article  CAS  Google Scholar 

  2. Smith, J. B. & Willis, A. L. Nature new Biol. 231, 235–237 (1971).

    Article  CAS  Google Scholar 

  3. Roth, G. J. & Majerus, P. W. J. clin. Invest. 56, 624–632 (1975).

    Article  CAS  Google Scholar 

  4. Patrono, C. et al. Thromb. Res. 17, 317–327 (1980).

    Article  CAS  Google Scholar 

  5. Marcus, A.J. New Engl. J. Med. 297, 1284–1285 (1977).

    Article  CAS  Google Scholar 

  6. Burch, J. W., Baenziger, N. L., Stanford, N. & Majerus, P. W. Proc. natn. Acad. Sci. U.S.A. 75, 5181–5184 (1978).

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

  8. Gryglewski, R.J., Bunting, S., Moncada, S., Flower, R.J. & Vane, J.R. Prostaglandins 12, 685–713 (1976).

    Article  CAS  Google Scholar 

  9. Blair, I. A., Barrow, S. E., Waddell, K. A., Lewis, P.J. & Dollery, C. T. Prostaglandins 23, 579–589 (1982).

    Article  CAS  Google Scholar 

  10. Hong, S. L. Thromb. Res. 18, 789–795 (1980).

    Article  Google Scholar 

  11. Barrow, S.E. et al. Br. J. Pharmac. (in the press).

  12. Waddell, K. A. et al. Int. J. Mass Spectrom. ion Phys. 48, 233–236 (1983).

    Article  ADS  CAS  Google Scholar 

  13. Ritter, J. M., Barrow, S. E., Blair, I. A. & Dollery, C. T. Lancet i, 317–319 (1983).

    Article  Google Scholar 

  14. Dollery, C. T. et al. Atherosclerosis: Mechanisms and Approaches to Therapy 105–123 (ed. Miller, N. E.) (Raven, New York, 1983).

    Google Scholar 

  15. Czervionke, R. L., Hoak, J. C. & Haycraft, D.L. J. clin. Invest. 63, 1089–1092 (1979).

    Article  CAS  Google Scholar 

  16. Jaffe, E. A. & Weksler, B. B. J. clin. Invest. 63, 532–535 (1979).

    Article  CAS  Google Scholar 

  17. Dejana, E. et al. Biochem. Pharmac. 32, 710–713 (1983).

    Article  CAS  Google Scholar 

  18. Seymour, R. A. & Rawlins, M. D. Br. J. clin. Pharmac. 13, 807–810 (1982).

    Article  CAS  Google Scholar 

  19. FitzGerald, G. A. et al. J. clin. Invest. 71, 676–688 (1983).

    Article  CAS  Google Scholar 

  20. Weksler, B. B. et al. New Engl. J. Med. 308, 800–805 (1983).

    Article  CAS  Google Scholar 

  21. Preston, F. E. et al. New Engl. J. Med. 304, 76–79 (1981).

    Article  CAS  Google Scholar 

  22. Hanley, S. P., Cockbill, S. R., Bevan, J. & Heptinstall, S. Lancet i, 969–971 (1981).

    Article  Google Scholar 

  23. Moncada, S., Herman, A. G., Higgs, E. A. & Vane, J. R. Thromb. Res. 11, 323–344 (1977).

    Article  CAS  Google Scholar 

  24. Baenziger, N. L., Becherer, P. R. & Majerus, P. W. Cell 16, 967–974 (1979).

    Article  CAS  Google Scholar 

  25. Dusting, G. J. & Nolan, R. D. Br. J. Pharmac. 74, 553–562 (1981).

    Article  CAS  Google Scholar 

  26. Whittle, B. J. R., Higgs, G. A., Eakins, K. E., Moncada, S. & Vane, J. R. Nature 284, 271–273 (1980).

    Article  ADS  CAS  Google Scholar 

  27. Weksler, B. B., Tack-Goldman, K., Subramanian, V. A. & Gay, W. A. Circulation 71, 332–340 (1985).

    Article  CAS  Google Scholar 

  28. DeWitt, D. L., Day, J. S., Sonnenburg, W. K. & Smith, W. L. J. clin. Invest. 72, 1882–1888 (1983).

    Article  CAS  Google Scholar 

  29. Moncada, S. Br. J. Pharmac. 76, 3–31 (1982).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heavey, D., Barrow, S., Hickling, N. et al. Aspirin causes short-lived inhibition of bradykinin-stimulated prostacyclin production in man. Nature 318, 186–188 (1985). https://doi.org/10.1038/318186a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/318186a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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