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-PGF1α) 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
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
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
Ferreira, S. H., Moncada, S. & Vane, J. R. Nature new Biol. 231, 237–239 (1971).
Smith, J. B. & Willis, A. L. Nature new Biol. 231, 235–237 (1971).
Roth, G. J. & Majerus, P. W. J. clin. Invest. 56, 624–632 (1975).
Patrono, C. et al. Thromb. Res. 17, 317–327 (1980).
Marcus, A.J. New Engl. J. Med. 297, 1284–1285 (1977).
Burch, J. W., Baenziger, N. L., Stanford, N. & Majerus, P. W. Proc. natn. Acad. Sci. U.S.A. 75, 5181–5184 (1978).
Moncada, S., Gryglewski, R., Bunting, S. & Vane, J.R. Nature 263, 663–665 (1976).
Gryglewski, R.J., Bunting, S., Moncada, S., Flower, R.J. & Vane, J.R. Prostaglandins 12, 685–713 (1976).
Blair, I. A., Barrow, S. E., Waddell, K. A., Lewis, P.J. & Dollery, C. T. Prostaglandins 23, 579–589 (1982).
Hong, S. L. Thromb. Res. 18, 789–795 (1980).
Barrow, S.E. et al. Br. J. Pharmac. (in the press).
Waddell, K. A. et al. Int. J. Mass Spectrom. ion Phys. 48, 233–236 (1983).
Ritter, J. M., Barrow, S. E., Blair, I. A. & Dollery, C. T. Lancet i, 317–319 (1983).
Dollery, C. T. et al. Atherosclerosis: Mechanisms and Approaches to Therapy 105–123 (ed. Miller, N. E.) (Raven, New York, 1983).
Czervionke, R. L., Hoak, J. C. & Haycraft, D.L. J. clin. Invest. 63, 1089–1092 (1979).
Jaffe, E. A. & Weksler, B. B. J. clin. Invest. 63, 532–535 (1979).
Dejana, E. et al. Biochem. Pharmac. 32, 710–713 (1983).
Seymour, R. A. & Rawlins, M. D. Br. J. clin. Pharmac. 13, 807–810 (1982).
FitzGerald, G. A. et al. J. clin. Invest. 71, 676–688 (1983).
Weksler, B. B. et al. New Engl. J. Med. 308, 800–805 (1983).
Preston, F. E. et al. New Engl. J. Med. 304, 76–79 (1981).
Hanley, S. P., Cockbill, S. R., Bevan, J. & Heptinstall, S. Lancet i, 969–971 (1981).
Moncada, S., Herman, A. G., Higgs, E. A. & Vane, J. R. Thromb. Res. 11, 323–344 (1977).
Baenziger, N. L., Becherer, P. R. & Majerus, P. W. Cell 16, 967–974 (1979).
Dusting, G. J. & Nolan, R. D. Br. J. Pharmac. 74, 553–562 (1981).
Whittle, B. J. R., Higgs, G. A., Eakins, K. E., Moncada, S. & Vane, J. R. Nature 284, 271–273 (1980).
Weksler, B. B., Tack-Goldman, K., Subramanian, V. A. & Gay, W. A. Circulation 71, 332–340 (1985).
DeWitt, D. L., Day, J. S., Sonnenburg, W. K. & Smith, W. L. J. clin. Invest. 72, 1882–1888 (1983).
Moncada, S. Br. J. Pharmac. 76, 3–31 (1982).
Author information
Authors and Affiliations
Rights 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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/318186a0
This article is cited by
-
The association between acetylsalicylic acid and subarachnoid haemorrhage: the Framingham Heart Study
Scientific Reports (2023)
-
Aspirin and Subarachnoid Haemorrhage in the UK Biobank
Translational Stroke Research (2023)
-
Oral single high‐dose aspirin results in a long‐lived inhibition of anodal current‐induced vasodilatation
British Journal of Pharmacology (2002)
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.