Biological significance and therapeutic potential of prostacyclin

  • S. Moncada
  • J. R. Vane


Prostacyclin and thromboxane A2 (TXA2) are both derived from arachidonic acid, a fatty acid present in the phospholipids of cell membranes. TXA2 is an unstable (t1/2 30s at 37 °C), powerful vasoconstrictor agent generated by platelets1. Prostacyclin is also unstable (t1/2 3 min at 37 °C) but induces vasodilatation and inhibits platelet aggregation. Prostacyclin and thromboxane A2 represent, therefore, the opposite poles of a homeostatic mechanism for regulation of platelet aggregability in vivo. Manipulation of this control mechanism will affect thrombus and haemostatic plug formation.


Peripheral Artery Disease Inhibit Platelet Aggregation Prostaglandin Endoperoxide Prostacyclin Production Arteriosclerosis Obliterans 
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  1. 1.
    Hamberg, M. and Samuelsson, B. (1974). Novel transformations of arachidonic acid in human platelets. Proc. Natl. Acad. Sci., USA, 71, 3400PubMedCrossRefGoogle Scholar
  2. 2.
    Vane, J.R. (1971). Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol231, 232Google Scholar
  3. 3.
    Moncada, S. and Vane, J.R. (1979). Pharmacology and endogenous roles of prosta-glandin endoperoxides, thromboxane A2 and prostacyclin. Pharm. Rev., 30, 293Google Scholar
  4. 4.
    Tateson, J.E., Moncada, S. and Vane, J.R. (1977). Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins, 13, 389PubMedCrossRefGoogle Scholar
  5. 5.
    Gorman, R.R., Bunting, S. and Miller, O.V. (1977). Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins, 13, 377PubMedCrossRefGoogle Scholar
  6. 6.
    Miller, O. V. and Gorman, R. R. (1976). Modulation of platelet cyclic nucleotide content by PGE1 and the prostaglandin endoperoxide PGG2. J. Cyclic Nucl. Res., 2, 79Google Scholar
  7. 7.
    Dusting, G. J., Moncada, S. and Vane, J. R. (1977). Disappearance of prostacyclin in the circulation of the dog. Br. J. Pharmacol., 62, 414 PGoogle Scholar
  8. 8.
    Gryglewski, R. J., Korbut, R. and Ocetkiewicz, A.C. (1978). Generation of prostacyclin by lungs in vivo and its release into the arterial circulation. Nature (Lond.), 273, 765Google Scholar
  9. 9.
    Moncada, S., Korbut, R., Bunting, S. and Vane, J. R. (1978). Prostacyclin is a circulating hormone. Nature (Lond.), 273, 767CrossRefGoogle Scholar
  10. 10.
    Hensby, C.N., Barnes, P. J., Dollery, C.T. and Dargie, H. (1979). Production of 6-oxo- PGFla by human lung in vivo. Lancet, 2, 1162PubMedCrossRefGoogle Scholar
  11. 11.
    Moncada, S., Herman, A.G., Higgs, E.A. and Vane, J.R. (1977). Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the anti-thrombotic properties of vascular endothelium. Thromb. Res., 11, 323PubMedCrossRefGoogle Scholar
  12. 12.
    Higgs, E.A., Moncada, S., Vane, J.R., Caen, J. P., Michel, H. and Tobelem, G. (1978). Effect of prostacyclin (PGI2) on platelet adhesion to rabbit arterial subendothelium. Prostaglandins, 16, 17PubMedCrossRefGoogle Scholar
  13. 13.
    Moncada, S., Gryglewski, R.J., Bunting, S. and Vane, J.R. (1976). A lipid peroxide inhibits the enzyme in blood vessel microsomes that generates from prostaglandin endoperoxides the substance (prostaglandin X) which prevents platelet aggregation. Prostaglandins, 12, 715PubMedCrossRefGoogle Scholar
  14. 14.
    Slater, T.F. (1972). Free Radical Mechanisms in Tissue Injury. ( London: Pion Ltd )Google Scholar
  15. 15.
    Glavind, J., Hartmann, S., Clemmesen, J., Jessen, K.E. and Dam, H. (1952). Studies on the role of lipoperoxides in human pathology. II. The presence of per oxidised lipids in the atherosclerotic aorta. Acta. Pathol. Microbiol. Scand., 30, 1PubMedCrossRefGoogle Scholar
  16. 16.
    Dembinska-Kiec, A., Gryglewska, T., Zmuda, A. and Gryglewski, R.J. (1977). The generation of prostacyclin by arteries and by the coronary vascular bed is reduced in experimental atherosclerosis in rabbit. Prostaglandins, 14, 1025PubMedCrossRefGoogle Scholar
  17. 17.
    Angelo, V.D., Villa, S., Mysliwiec, M., Donati, M.B. and De Gaetano, G. (1978). Defective fibrinolytic and prostacyclin-like activity in human atheromatous plaques. Thromb. Diath. Haemorrh., 39, 535Google Scholar
  18. 18.
    Woodford, F.P., Bottcher, C.J.F., Oette, K. and Ahrens, E.H. Jr. (1965). The artifactual nature of lipid peroxides detected in extracts of human aorta. J. Atheroscler. Res., 5, 311PubMedCrossRefGoogle Scholar
  19. 19.
    Iwakami, M. (1965). Peroxides as a factor of atherosclerosis. Nagoya J. Med. Sci., 28, 50PubMedGoogle Scholar
  20. 20.
    Nordoy, A., Svensson, B., Wiebe, D. and Hoak, J.C. (1978). Lipoproteins and the inhibitory effect of human endothelial cells on platelet function. Circ. Res., 43, 527PubMedGoogle Scholar
  21. 21.
    Lagarde, M. and Dechavanne, M. (1977). Increase of platelet prostaglandin cyclic endoperoxides in thrombosis. Lancet, 1, 88PubMedCrossRefGoogle Scholar
  22. 22.
    Shimamoto, T., Kobayashi, M., Takahashi, T., Takashima, Y., Sakamoto, M. and Morooka, S. (1978). An observation of thromboxane A2 in arterial blood after cholesterol feeding in rabbits. Jpn. Heart J., 19, 748PubMedCrossRefGoogle Scholar
  23. 23.
    Szczeklik, A., Gryglewski, R.J., Musial, J., Grodzinska, L., Serwonska, M. and Marcinkiewicz, E. (1978). Thromboxane generation and platelet aggregation in survivals of myocardial infarction. Thromb. Diath. Haemorrh., 40, 66Google Scholar
  24. 24.
    Lewy, R.I., Smith, J.B., Silver, M. J., Saia, J., Walinsky, P. and Wiener, L. (1979). Detection of thromboxane B2 in peripheral blood of patients with Prinzmetal’s angina. Prostaglandins Med., 2, 243PubMedCrossRefGoogle Scholar
  25. 25.
    Harrison, H.E., Reece, A.H. and Johnson, M. (1978). Decreased vascular prostacyclin in experimental diabetes. Life Sci., 23, 351PubMedCrossRefGoogle Scholar
  26. 26.
    Johnson, M., Reece, A.H. and Harrison, H.E. (1978). Decreased vascular prostacyclin in experimental diabetes. 7th Int. Cong. Pharmacology, Paris, Abstracts, p. 342. ( Oxford: Pergamon Press )Google Scholar
  27. 27.
    Johnson, M., Harrison, H.E., Raftery, A.T. and Elder, J.B. (1979). Vascular prostacyclin may be reduced in diabetes in man. Lancet, 1, 325PubMedCrossRefGoogle Scholar
  28. 28.
    Dollery, C.T., Friedman, L. A., Hensby, C.N., Kohner, E., Lewis, P. J., Porta, M. and Webster, J. (1979). Circulating prostacyclin may be reduced in diabetes. Lancet, 2, 1365PubMedCrossRefGoogle Scholar
  29. 29.
    Remuzzi, G., Cavenaghi, A.E., Mecca, G., Donati, M.B. and De Gaetano, G. (1977). Prostacyclin (PGI2) and bleeding time in uremic patients. Thromb. Res., 11, 919PubMedCrossRefGoogle Scholar
  30. 30.
    Remuzzi, G., Misiani, R., Marchesi, D., Livio, M., Mecca, G., De Gaetano, G. and Donati, M.B. (1978). Haemolytic-uraemic syndrome: deficiency of plasma factor(s) regulating prostacyclin activity. Lancet, 2, 871PubMedCrossRefGoogle Scholar
  31. 31.
    Maclntyre, D.E., Pearson, J.J. and Gordon, J.L. (1978). Localisation and stimulation of prostacyclin production in vascular cells. Nature (Lond.), 271, 549CrossRefGoogle Scholar
  32. 32.
    Pace-Asciak, C. R., Carrara, M. C., Rangaraj, G. and Nicolaou, K. G. (1978). Enhanced formation of PGI2, a potent hypotensive substance, by aortic rings and homogenates of the spontaneously hypertensive rat. Prostaglandins, 15, 1005PubMedCrossRefGoogle Scholar
  33. 33.
    Moncada, S. and Vane, J.R. (1979). Arachidonic acid metabolites and the interactions between platelets and blood vessel walls. N. Engl. J. Med., 300, 1142PubMedCrossRefGoogle Scholar
  34. 34.
    Branthwaite, M. A. (1972). Neurological damage related to open heart surgery. Thorax, 27, 748PubMedCrossRefGoogle Scholar
  35. 35.
    Griffith, G.C., Nichols, G., Asher, J. D. and Flanagan, B. (1965). Heparin osteoporosis. J. Am. Med. Assoc., 193, 91CrossRefGoogle Scholar
  36. 36.
    Balanowski, P. J. P., Bauer, J., Machiedo, G. and Neville, W.E. (1977). Prostaglandin influence on pulmonary intravascular leukocytic aggregation during cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg., 73, 221Google Scholar
  37. 37.
    Ubatuba, F. B., Moncada, S. and Vane, J. R. (1979). The effect of prostacyclin (PGI2) on platelet behaviour, thrombus formation in vivo and bleeding time. Thromb. Diath. Haemorrh., 41, 425Google Scholar
  38. 38.
    Robert, A., Hanchar, A. J., Lancaster, C. and Nezamis, J.E. (1979). Prostaglandin inhibits enteropooling and diarrhea. In Vane, J.R. and Bergstrom, S. (eds.), Prostacyclin, pp. 147–158. ( New York: Raven Press )Google Scholar
  39. 39.
    Woods, H. F., Ash, G., Weston, M. J., Bunting, S., Moncada, S. and Vane, J. R. (1978). Prostacyclin can replace heparin in haemodialysis in dogs. Lancet, 2, 1075PubMedCrossRefGoogle Scholar
  40. 40.
    Coppe, D., Wonders, T., Snider, M. and Salzman, E. W. (1979). Preservation of platelet number and function during extracorporeal membrane oxygenation (ECMO) by regional infusion of prostacyclin. In Vane, J.R. and Bergstrom, S. (eds.), Prostacyclin, pp. 371–383. ( New York: Raven Press )Google Scholar
  41. 41.
    Bunting, S., Moncada, S., Vane, J.R., Woods, H.F. and Weston, M.J. (1979). Prostacyclin improves hemocompatibility during charcoal hemoperfusion. In Vane, J. R. and Bergstrom, S. (eds.), Prostacyclin, pp. 361–369. ( New York: Raven Press )Google Scholar
  42. 42.
    Gimson, A.E.S., Hughes, R.D., Mellon, P. J., Woods, H.F., Langley, P.G., Canalese, J., Williams, R. and Weston, M.J. (1980). Prostacyclin to prevent platelet activation during charcoal haemoperfusion in fulminant hepatic failure. Lancet, 1, 173PubMedCrossRefGoogle Scholar
  43. 43.
    Carlson, L.A. and Olsson, A.G. (1976). Intravenous prostaglandin Ej in severe peripheral vascular disease. Lancet, 2, 810PubMedCrossRefGoogle Scholar
  44. 44.
    Szczeklik, A., Nizankowski, R., Skawinski, S., Szczeklik, J., Gluszko, P. and Gryglewski, R.J. (1979). Successful therapy of advanced arteriosclerosis obliterans with prostacyclin. Lancet, 1, 1111PubMedCrossRefGoogle Scholar
  45. 45.
    Szczeklik, A., Gryglewski, R.J., Nizankowski, R., Skawinski, S., Gluszko, P. and Korbut, R. (1980). Prostacyclin therapy in peripheral artery disease. Thromb. Res., 19, 191PubMedCrossRefGoogle Scholar

Copyright information

© MTP Press Limited 1982

Authors and Affiliations

  • S. Moncada
  • J. R. Vane

There are no affiliations available

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