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Thromb Haemost 1979; 41(02): 425-435
DOI: 10.1055/s-0038-1646791
Original Articles
Schattauer GmbH Stuttgart

The Effect of Prostacyclin (PGI2) on Platelet Behaviour. Thrombus Formation in Vivo and Bleeding Time

Fernando B Ubatuba
The Department of Prostaglandin Research, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS England
,
Salvador Moncada
The Department of Prostaglandin Research, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS England
,
John R Vane
The Department of Prostaglandin Research, Wellcome Research Laboratories, Langley Court, Beckenham, Kent BR3 3BS England
› Author Affiliations
Further Information

Publication History

Received 06 January 1978

Accepted 29 April 1978

Publication Date:
09 July 2018 (online)

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Summary

Prostacyclin (PGI2) infused intravenously into anaesthetized rabbits inhibited electrically-induced thrombus formation in the carotid artery, increased bleeding time and inhibited ex vivo platelet aggregation induced by ADP or arachidonic acid. The increase in bleeding time and the inhibition of ex vivo platelet aggregation lasted for as long as the infusion of PGI2 was maintained but rapidly disappeared after infusion was stopped.

Prostacyclin is a more potent inhibitor of platelet function, in vivo than prostaglandin E1 (PGE1) or prostaglandin D2 (PGD2).

The effects of prostacyclin on all parameters studied except blood pressure were potentiated by the concomitant administration of theophylline, a phosphodiesterase inhibitor.

 

  • References

  • 1 Armstrong JM, Lattimer N, Moncada S, Vane JR. 1978; Comparison of the vasopressor effects of prostacyclin and 6-oxo-prostaglandin Flαwith those of prostaglandin E2in rats and rabbits. British Journal of Pharmacology 62: 125
    CrossrefPubMedGoogle Scholar
  • 2 Chandrasekhar N. 1967; Inhibition of platelet aggregation by prostaglandins. Blood 30: 554
    PubMedGoogle Scholar
  • 3 Dusting GJ, Moncada S, Vane JR. 1978; Disappearance of prostacyclin in the circulation of the dog. British Journal of Pharmacology 62: 414
    PubMedGoogle Scholar
  • 4 Emmons PR, Hampton JR, Harrison MJ G, Honour AJ, Mitchell JR A. 1967; Effect of prostaglandin E1on platelet behaviour in vitro and in vivo. British Medical Journal 2: 468
    CrossrefPubMedGoogle Scholar
  • 5 Ferreira SH, Vane JR. 1967; Prostaglandins: Their disappearance from and release into the circulation. Nature 216: 868
    CrossrefPubMedGoogle Scholar
  • 6 Gorman RR, Bunting S, Miller OV. 1977; Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins 13: 377
    CrossrefPubMedGoogle Scholar
  • 7 Gryglewski RJ, Bunting S, Moncada S, Flower RJ, Vane JR. 1976; Arterial walls are protected against deposition of platelet thrombi by a substance (Prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 12: 685
    CrossrefPubMedGoogle Scholar
  • 8 Herrmann RG, Lacefield WB. 1974. Effect of antithrombotic drugs on in vivo experimental thrombosis. In: Sherry S, Scriabine A. (eds.) Platelets and Thrombosis. University Park Press; London; p 203
    Google Scholar
  • 9 Holmes IB, Smith GM, Freuler F. 1977; The effect of intravenous adenosine diphosphate on the number of circulating platelets in experimental animals: Inhibition by Prostaglandin E1Dipyridamole, SH-869 and VK-774. Thrombosis and Haemostasis 37: 36
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Johnson RA, Morton DR, Kinner JH, Gorman RR, Mcguire JC, Sun FF, Whittaker N, Bunting S, Salmon JA, Moncada S, Vane JR. 1976; The chemical characterization of prostaglandin X (prostacyclin). Prostaglandins 12: 915
    CrossrefPubMedGoogle Scholar
  • 11 Johnson RA, Lincoln FH, Thompson JL, Nidy EG, Mizsak SA, Axen U. 1977; Synthesis and stereochemistry of prostacyclin and synthesis of 6-keto prostaglandin Flα . Journal of the American Chemical Society 99: 12
    PubMedGoogle Scholar
  • 12 Kinlough-Rathbone RL, Packham MA, Mustard JF. 1970; The effect of prostaglandin E1on platelet function in vitro and in vivo. British Journal of Haematology 19: 559
    CrossrefPubMedGoogle Scholar
  • 13 Moncada S, Gryglewski RJ, Bunting S, Vane JR. 1976; a An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663
    CrossrefPubMedGoogle Scholar
  • 14 Moncada S, Gryglewski RJ, Bunting S, Vane JR. 1976; b 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: 715
    CrossrefPubMedGoogle Scholar
  • 15 Mustard JF, Packham MA. 1975; Platelets, thrombosis and drugs. Drugs 9: 19
    CrossrefPubMedGoogle Scholar
  • 16 Reynolds ES. 1963; The use of lead citrate at high pH as an electron opaque stain in electron microscopy. J. Cell Biol 17: 208
    CrossrefPubMedGoogle Scholar
  • 17 Smith JB, Silver MJ, Ingerman CM, Kocsis JJ. 1974; Prostaglandin D2inhibits the aggregation of human platelets. Thrombosis Research 5: 291
    CrossrefPubMedGoogle Scholar
  • 18 Stibbe J, Ong GL, Ten Hoor F, Nauta J. 1973. The influence of PGE1on platelet decrease in the heart-lung machine. In: IVth International Congress on Thrombosis and Haemostasis. Vienna: Abstract p 412
    Google Scholar
  • 19 Tateson JE, Moncada S, Vane JR. 1977; Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins 13: 389
    CrossrefPubMedGoogle Scholar
  • 20 Whittaker N. 1977; A synthesis of prostacyclin sodium salt. Tetrahedron Letters 32: 2805
    PubMedGoogle Scholar
  • 21 Whittle BJ R, Moncada S, Vane JR. 1977; Comparison of the effects of prostacyclin (PGI2), prostaglandin E1and D2on platelet aggregation in different species. Prostaglandins 16: 373
    PubMedGoogle Scholar