Advertisement

Prostacyclin

  • S. Moncada
  • J. R. Vane
Part of the NATO Advanced Study Institutes Series book series

Abstract

In 1976, the Wellcome group discovered that prostaglandin endoperoxides were transformed by a microsomal enzyme from blood vessels into an unstable substance which is a potent vasodilator and an inhibitor of platelet aggregation (13,14, 75,76, 42). This compound originally called PGX was later chemically identified as an intermediate in the formation of 6-oxo-PGF, a compound described earlier (95). PGX was then renamed prostacyclin and given the abbreviation of PGI2 (61).

Keywords

Arachidonic Acid Platelet Aggregation Thrombus Formation Bleeding Time Renin Release 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    R. M. Abel, M. J. Buckley, W. G. Austen, G. O. Barrett, C. H. Beck and J. E. Fischer, Etiology, incidence and prognosis of renal failure following cardiac operations. J. Thorac. Cardiovasc. Surg., 71: 323–333 (1976)PubMedGoogle Scholar
  2. 2.
    J. L. Amezcua, M. Parsons and S. Moncada, Unstable metabolites of arachidonic acid, aspirin and the formation of the haemostatic plug. Thromb. Res., 13: 477–488 (1978)PubMedCrossRefGoogle Scholar
  3. 3.
    J. L. Amezcua, J. O’Grady, J. A. Salmon and S. Moncada, Prolonged paradoxical effect of aspirin on platelet behavious and bleeding time in man. Thromb. Res., 16: 69–79 (1979)PubMedCrossRefGoogle Scholar
  4. 4.
    J. M. Armstrong, D. J. Chapple, G. J. Dusting, R. Hughes, S. Moncada and J. R. Vane, Cardiovascular actions of prostacyclin (PGI2) in chloralose anaesthetized dogs.Br. J. Pharmac., 61: 136P (1977)Google Scholar
  5. 5.
    J. M. Armstrong, N. Lattimer, S. Moncada and J. R. Vane, Comparison of the vasodepressor effects of prostacyclin and 6-oxo-prostaglandin Fla with those of prostaglandin E2 in rats and rabbits. Br. J. Pharmac., 62: 125–130 (1978)CrossRefGoogle Scholar
  6. 6.
    N. L. Baenziger, M. J. Dillender and P. W. Majerus, Cultured human skin fibroblasts and arterial cells produce a labile platelet-inhibitory prostaglandin. Biochem. Biophys. Res. Commun., 78: 294–301 (1977)PubMedCrossRefGoogle Scholar
  7. 7.
    L. C. Best, T. J. Martin, R. G. G. Russell and F. E. Preston, Prostacyclin increases cyclic AMP levels and adenylate cyclase activity in platelets. Nature (Loud.), 267: 850–851 (1977)CrossRefGoogle Scholar
  8. 8.
    G. J. Blackwell, R. J. Flower, N. Russell-Smith, J. A. Salmon, P. B. Thorogood and J. R. Vane, 1-n-Butylimidazole: a potent and selective inhibitor of “Thromboxane Synthetase”. Br. J. Pharmac., 64: 436P (1978)Google Scholar
  9. 9.
    A. J. Block, H. Feinberg, K. Herbaczynska-Cedro and J. R. Vane, Anoxia induced release of prostaglandins in rabbit isolated heart. Circ. Res., 36: 34–42 (1975)PubMedCrossRefGoogle Scholar
  10. 10.
    P. M. Bolger, G. M. Eisner, P. W. Ramwell and L. M. Slotkoff, Renal actions of prostacyclin. Nature (Lond.), 271: 457–469 (1978)Google Scholar
  11. 11.
    D. J. Boullin, S. Bunting, W. P. Blaso, T. M. Hunt and S. Moncada, Responses of human and baboon arteries to prostaglandin endoperoxides and biologically generated and synthetic prostacyclin: their relevance to cerebral arterial spasm in man. Br. J. Clin. Pharmac., 7: 139–147 (1979)CrossRefGoogle Scholar
  12. 12.
    M. A. Branthwaite, Neurological damage related to open heart surgery. Thorax, 27: 748–753 (1972)PubMedCrossRefGoogle Scholar
  13. 13.
    S. Bunting, R. Gryglewski, S. Moncada and J. R. Vane, Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregation. Prostaglandins, 12: 897–913 (1976)PubMedGoogle Scholar
  14. 14.
    S. Bunting, S. Moncada and J. R. Vane, Antithrombotic properties of vascular endothelium. Lancet, ii: 1075–1076 (1977)Google Scholar
  15. 15.
    J. W. Burch, N. Stanford and P. W. Majerus, Inhibition of platelet prostaglandin synthetase by oral aspirin. J. Clin. Invest., 61: 314–319 (1978)PubMedCrossRefGoogle Scholar
  16. 16.
    D. J. Chapple, G. J. Dusting, R. Hughes and J. R. Vane, A vagal reflex contributes to the hypotensive effect of prostacyclin in anaesthetized dogs. J. Physiol., 281: 43–44P (1978)Google Scholar
  17. 17.
    D. J. Chapple, G. J. Dusting, R. Hughes and J. R. Vane, Some direct and reflex cardiovascular actions of prostacyclin (PGI2) and PGE2 in anaesthetized dogs. Br. J. Pharmac., in press (1979)Google Scholar
  18. 18.
    G. J. Christofinis, S. Moncada, C. MacCormick, S. Bunting and J. R. Vane, Prostacyclin (PGI2) release by rabbit aorta and human umBilical vein endothelial cells after prolonged subculture. Weibel-Palade bodies were observed in low and high passages of these cells. In: Prostacyclin, J. R. Vane and S. Bergstrom, , Raven Press, New York, in press (1979)Google Scholar
  19. 19.
    F. Coceani, I. Bishai, E. White, E. Bodack and P. M. 011ey, Action of prostaglandins, endoperoxides and thromboxanes on the lamb ductus arteriosus. Am. J. Physiol., 234: H117 - H112 (1978)PubMedGoogle Scholar
  20. 20.
    R. L. Czervionke, J. C. Hoak, and G. Fry, Effect of aspirin on thrombin-induced adherence of platelets to cultured cells from the blood vessel wall. J. Clin. Invest., 62: 847–856 (1978)PubMedCrossRefGoogle Scholar
  21. 21.
    R. L. Czervionke, J. B. Smith, G. L. Fry and J. C. Hoak, Inhibition of prostacyclin by treatment of endothelium with aspirin. J. Clin. Invest., 63: 1089–1092 (1979)PubMedCrossRefGoogle Scholar
  22. 22.
    V. D’Angelo, S. Villa, M. Mysliwiec, M. B. Donati and G. De Gaetano, Defective fibrinolytic and prostacyclin-like activity in human atheromatous plaques. Thromb. Haem., 39: 535–536 (1978)Google Scholar
  23. 23.
    J. L. Data, W. J. Crump, J. W. Hollifield, J. C. Frolich and A. S. Nies, Prostaglandins: a role in baroreceptor control of renin release. Clin. Res., 24: 397A (1976)Google Scholar
  24. 24.
    E. A. M. De Dekere, D. H. Nugteren and F. Ten Hoor, Prostacyclin is the major prostaglandin released from the isolated perfused rabbit and rat heart. Nature (Lond.), 268: 160–163 (1977)CrossRefGoogle Scholar
  25. 25.
    A. Dembinska-Kiec, T. Gryglewska, A. Zmuda and R. J. Gryglewski, The generation of prostacyclin by arteries and by the coronary vascular bed is reduced in experimental atherosclerosis in rabbits. Prostaglandins, 14: 1025–1054 (1977)PubMedGoogle Scholar
  26. 26.
    G. J. Dusting,D. J. Chapple, R. Hughes, S. Moncada and J. R. Vane, Prostacyclin induces coronary vasodilatation in anaesthetized dogs. Cardiovasc. Res., 12: 720–730 (1978c)Google Scholar
  27. 27.
    G. J. Dusting, S. Moncada and J. R. Vane, Prostacyclin (PGX) is the endogenous metabolite responsible for relaxation of coronary arteries induced by arachidonic acid. Prostaglandins, 13: 3–15 (1977a)PubMedGoogle Scholar
  28. 28.
    G. J. Dusting, S. Moncada and J. R. Vane, Disappearance of prostacyclin in the circulation of the dog. Br. J. Pharmac., 62: 414–415P (1977b)Google Scholar
  29. 29.
    G. J. Dusting, S. Moncada and J. R. Vane, Prostacyclin is a weak contractor of coronary arteries in the pig. Eur. J. Pharmac., 45: 301–304 (1977c)CrossRefGoogle Scholar
  30. 30.
    G. J. Dusting, S. Moncada and J. R. Vane, Recirculation of prostacyclin (PGI2) in the dog. Br. J. Pharmacol., 64: 315320 (1978a)Google Scholar
  31. 31.
    G. J. Dusting, S. Moncada and J. R. Vane, Vascular actions of arachidonic acid and its metabolites in perfused mesenteric and femoral beds of the dog. Eur. J. Pharmac., 49: 65–72 (1978b)CrossRefGoogle Scholar
  32. 32.
    J. Dyerberg, H. 0. Bang, E. Stoffersen, S. Moncada and J. R. Vane, Polyunsaturated fatty acids, atherosclerosis and thrombosis. Lancet, ii: 117–119 (1978)Google Scholar
  33. 33.
    J. Dyerberg and H. 0. Bang, Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet, ií: 433–435 (1979)Google Scholar
  34. 34.
    S. H. Ferreira and J. R. Vane, Prostaglandins: their disappearance from and release into the circulation. Nature (Lond.), 216: 868–873 (1967)CrossRefGoogle Scholar
  35. 35.
    J. C. Frolich, J. W. Hollifield, J. C. Dormois, B. L. Frolich, H. Seyberth, A. M. Michelakis and J. A. Oates, Suppression of plasma renin activity by indomethacin in man. Circ. Res., 39: 447–452 (1976)PubMedCrossRefGoogle Scholar
  36. 36.
    J. G. Gerber, R. A. Branch, A. S. Nies, J. F. Gerkens, D. G. Shand, J. Hollifield and J. A. Oates, Prostaglandins and renin release: II.assessment of renin secretion following infusion of PGI2, E2 and D2 into the renal artery of anaesthetized dogs. Prostaglandins, 15: 81–88 (1978)PubMedGoogle Scholar
  37. 37.
    H. C. Godai, C. Eika, J. H. Dybdahl. L. Daae and S. Larsen, Aspirin and bleeding time. Lancet, i: 1236 (1979)Google Scholar
  38. 38.
    R. R. Gorman, S. Bunting and 0. V. Miller, Modulation of human platelet adenylate cyclase by prostacyclin (PGX). Prostaglandins, 13: 377–388 (1977)PubMedGoogle Scholar
  39. 39.
    R. R. Gorman, F. A. Fitzpatrick and 0. V. Miller, A selective thromboxane synthetase inhibitor blocks the cAMP lowering activity of PGH2. Biophys. Biochem. Res. Commun., 79: 305–313 (1977)Google Scholar
  40. 40.
    F. C. Grenier and W. L. Smith, Formation of 6-keto-PGF1 by collecting tubule cells isolated from rabbit renal papillae. Prostaglandins, 16: 759–772 (1978)Google Scholar
  41. 41.
    G. C. Griffith, C. Nichols, J. D. Asher and B. Flanagan, Heparin osteoporosis. J. Am. Med. Ass., 193: 91–94 (1965)CrossRefGoogle Scholar
  42. 42.
    R. Gryglewski, S. Bunting, S. Moncada, R. J. Flower and J. R. Vane, Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins 12: 685–714 (1976)PubMedGoogle Scholar
  43. 43.
    R. J. Gryglewski, R. Korbut and A. C. Ocetkiewicz, Deaggregatory action of prostacyclin in vivo and its enhancement by theophylline. Prostaglandins, 15: 637–644 (1978a)Google Scholar
  44. 44.
    R. J. Gryglewski, R. Korbut and A. Ocetkiewicz, Generation of prostacyclin by lungs in vivo and its release into the arterial circulation. Nature (Lond.), 273: 637–644 (1978b)CrossRefGoogle Scholar
  45. 45.
    R. J. Gryglewski, R. Korbut, A. Ocetkiewicz and T. Stachwa, In vivo method for quantitation of anti-platelet potency of drugs. Naunyn-Schmiedeberg’s Arch. Pharmac., 302:25 (1978)Google Scholar
  46. 46.
    R. J. Gryglewski, J. A. Salmon, F. B. Ubatuba, B. C. Weatherly, S. Moncada and J. R. Vane, Effects of all cis-5,8, 11,14,17 eicosapentaenoic acid and PGH3 on platelet aggregation. Prostaglandins, in press (1979)Google Scholar
  47. 47.
    R. J. Gryglewski, A. Szczeklik and R. Nizankowski, Anti-platelet action of intravenous infusion of prostacyclin in man. Thromb. Res., 13: 153–163 (1978)PubMedCrossRefGoogle Scholar
  48. 48.
    L. A. Harker, N. Joy, R. T. Wall, L. Quadracci and G. Striker, Inhibition of platelet reactivity by endothelial cells. Thromb. Haem. (Abstract), 38: 137 (1977)Google Scholar
  49. 49.
    L. A. Harker and S. J. Slichter, Platelet and fibrinogen consumption in man. New Eng. J. Med., 287: 999–1005 (1972)CrossRefGoogle Scholar
  50. 50.
    D. Harman and L. H. Piette, Free radical theory of ageing: Free radical reaction in serum. J. Gerontol., 21: 560 (1966)PubMedCrossRefGoogle Scholar
  51. 51.
    E. A. Higgs, S. Moncada, J. R. Vane, J. P. Caen, H. Michel and G. Tobelem, Effect of prostacyclin (PGI2) on platelet adhesion to rabbit arterial subendothelium. Prostaglandins, 16: 17–22 (1978)PubMedGoogle Scholar
  52. 52.
    G A. Higgs, S. Moncada and J. R. Vane, Prostacyclin (PGI2) inhibits the formation of platelet thrombi induced by adenosine diphosphate (ADP) in vivo. Br. J. Pharmacol., 61:137P (1977)Google Scholar
  53. 53.
    G. A. Higgs, S. Moncada and J. R. Vane, Microcirculatory effects of prostacyclin (PGI2) in the hamster cheek pouch. Microvasc. Res., in press (1979)Google Scholar
  54. 54.
    T. W. K. Hill, S. Moncada and J. R. Vane, Stimulation of renin release of protacyclin (PGI2) in anaesthetized dogs. Abstract for 7th International Congress of Pharmacology, Paris, July, 1978Google Scholar
  55. 55.
    T. W. K. Hill and S. Moncada, The renal haemodynamic and excretory actions of prostacyclin and 6-oxo-PGFla in anaesthetized dogs. Prostaglandins, 17: 87–98 (1979)PubMedGoogle Scholar
  56. 56.
    T. H. Hintze and G. Kaley, Prostaglandins and the control of blood flow in the canine myocardium. Circ. Res., 40: 313–320 (1977)CrossRefGoogle Scholar
  57. 57.
    T. H. Hintze, G. Kaley, E. G. Martin and E. J. Messina, PGI2 induces bradycardia in the dog. Prostaglandins, 15: p712 (1978)Google Scholar
  58. 58.
    A. J. Honour, T. D. R. Hockaday and J. I. Mann, The synergistic effect of aspirin and dipyridamole upon platelet thrombi in living blood vessels. Br. J. Exp. Path., 58: 268–272 (1977)Google Scholar
  59. 59.
    G. Hornstra, E. Haddeman and J. A. Don, Blood platelets do not provide endoperoxides for vascular prostacyclin production. Nature, 279: 66–68 (1979)PubMedCrossRefGoogle Scholar
  60. 60.
    A. L. Hyman, P. J. Kadowitz, W. E. M. Lands, C. G. Crawford, J. Fried and J. Barton, Coronary vasodilator activity of 13,14-dehydro prostacyclin methyl ester: comparison with prostacyclin and other prostanoids. Proc. Natl. Acad. Sci., USA, 75: 3522–3526 (1978)PubMedCrossRefGoogle Scholar
  61. 61.
    R. A. Johnson, D. R. Morton, J. H. Kinner, R. R. Gorman, J. C. McGuire, F. F. Sun, N. Whittaker, S. Bunting, J. A. Salmon, S. Moncada and J. R. Vane, The chemical structure of prostaglandin X (prostacyclin), Prostaglandins, 12: 915–928 (1976)PubMedGoogle Scholar
  62. 62.
    K. A. Jorgensen, A. S. Olesen, J. Dyerberg and E. Stoffersen, Aspirin and bleeding time: Dependency of Age. Lancet, ii: 302 (1979)Google Scholar
  63. 63.
    P. J. Kadowitz, B. M. Chapnick, L. P. Feigen, A. L. Hyman, P. K. Nelson and E. W. Spannhake, Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2. J. Appl. Physiol., 45: 408–413 (1978)PubMedGoogle Scholar
  64. 64.
    J. G. Kelton, J. Hirsh, C. J. Carter and M. R. Buchanan, Relationship to inhibition of vessel wall synthesis of prostaglandin I2-like activity. J. Clin. Invest., 62: 892895 (1978)Google Scholar
  65. 65.
    P. B. A. Kernoff, A. L. Willis, K. J. Stone, J. A. Davies and G. P. McNicol, Antithrombotic potential of dihomo-gammalinolenic acid in man. Br. Med. J., 2: 1441–1444 (1977)PubMedCrossRefGoogle Scholar
  66. 66.
    R. Korbut and S. Moncada, Prostacyclin (PGI2) and thromboxane A2 interaction in vivo. Regulation by aspirin and relationship with anti-thrombotic therapy. Thromb. Res., 13: 489–500 (1978)PubMedCrossRefGoogle Scholar
  67. 67.
    P. S. Kulkarni, R. Roberts and P. Needleman, Paradoxical endogenous synthesis of a coronary dilating substance from arachidonate. Prostaglandins, 123: 337–353 (1976)Google Scholar
  68. 68.
    C. Larsson, P. Weber and E. Anggard, Arachidonic acid increases and indomethacin decreases plasma renin activity in the rabbit. Eur. J. Pharmac., 28: 391–394 (1974)CrossRefGoogle Scholar
  69. 69.
    A. M. Lefer, M. L. Ogletree, J. B. Smith, M. J. Silver, K. C. Nicolaou, W. E. Barnette and G. P. Gasic, Prostacyclin: A potentially valuable agent for preserving myocardial tissues in acute myocardial ischaemia. Science, 200: 52–54 (1978)PubMedCrossRefGoogle Scholar
  70. 70.
    C. W. Leffler and J. R. Hessler, Pulmonary and systemic vascular effects of exogenous prostaglandin I2 in fetal lambs. Eur. J. Pharmac., 54: 37–42 (1979)CrossRefGoogle Scholar
  71. 71.
    S. V. Levy, Contractile responses to prostacyclin (PGI2) of isolated human saphenous and rat venous tissue. Prostaglandins, 16: 93–97 (1978)PubMedGoogle Scholar
  72. 72.
    D. E. MacIntyre, J. D. Pearson and J. L. Gordon, Localisation and stimulation of prostacyclin production in vascular cells. Nature, 271: 549–551 (1978)PubMedCrossRefGoogle Scholar
  73. 73.
    K. U. Malik and J. C. McGiff, Cardiovascular actions of prostaglandins. Prostaglandins: Physiological, Pharmacological and Pathological Aspects,S.M.Karim,ed., pp.103–200,MTP, LancasterGoogle Scholar
  74. 74.
    A. J. Marcus, B. B. Weksler and E. A. Jaffe, Enzymatic conversion of prostaglandin endoperoxide H2 and arachidonic acid to prostacyclin by cultured human endothelial cells. J. Biol. Chem., 253: 7138–7141 (1978)PubMedGoogle Scholar
  75. 75.
    S. Moncada, R. Gryglewski, S. Bunting and J. R. Vane, An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature (Lond.), 263: 663–665 (1976a)CrossRefGoogle Scholar
  76. 76.
    S. Moncada, R. J. Gryglewski, S. Bunting and J. R. Vane, 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: 715–733 (1976b)PubMedGoogle Scholar
  77. 77.
    S. Moncada, A. G. Herman, E. A. Higgs and J. R. Vane, 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: 323–344 (1977)PubMedCrossRefGoogle Scholar
  78. 78.
    S. Moncada, E. A. Higgs and J. R. Vane, Human arterial and venous tissues generate prostacyclin (prostaglandin X), a potent inhibitor of platelet aggregation. Lancet, i: 18–20 (1977)Google Scholar
  79. 79.
    S. Moncada and R. Korbut, Dipyridamole and other phosphodiesterase inhibitors act as anti-thrombotic agents through potentiating endogenous prostacyclin. Lancet, i: 1286–1289 (1978)Google Scholar
  80. 80.
    S. Moncada, R. Korbut, S. Bunting and J. R. Vane, Prostacyclin is a circulating hormone. Nature (Loud.), 273: 767–768 (1978)CrossRefGoogle Scholar
  81. 81.
    S. Moncada and J. R. Vane, The discovery of prostacyclin (PGX); a fresh insight into arachidonic acid metabolism. In: Biochemical Aspects of Prostaglandins and Thromboxanes, N. Kharasch and J. Fried, , pp.155–177, Academic Press, New York, San Francisco, London (1977)Google Scholar
  82. 82.
    S. Moncada and J. R. Vane, Unstable metabolites of arachidonic acid and their role in haemostasis and thrombosis. Br. Med. Bulletin, 34: 129–135 (1978)Google Scholar
  83. 83.
    S. Moncada and J. R. Vane, Arachidonic acid metabolites and the interactions between platelets and blood vessel walls. New Eng. J. Med., 300: 1142–1147 (1979a)CrossRefGoogle Scholar
  84. 84.
    S. Moncada and J. R. Vane, The role of prostacyclin in vascular tissue. Fed. Proc., 38: 62–66 (1979b)Google Scholar
  85. 85.
    K. M. Mullane, G. J. Dusting, J. A. Salmon, S. Moncada and J. R. Vane, Biotransformation and cardiovascular effects of arachidonic acid in the dog. Eur. J. Pharmac., 54: 217228 (1979)Google Scholar
  86. 86.
    K. M. Mullane, S. Moncada and J. R. Vane, Prostacyclin release induced by bradykinin may contribute to the anti-hypertensive action of angiotensin converting enzyme inhibitors. 4th Int. Prostaglandin Congress, Washington, 27–31st May, 1979, p. 84Google Scholar
  87. 87.
    P. Needleman, The synthesis and function of prostaglandins in the heart. Fed. Proc., 35:2376–2381 (1976). 88. P. Needleman, S. D. Bronson, A. Wyche, M. Sivakoff and K. C. Nicolaou, Cardiac and renal prostaglandin I2. J. Clin. Invest., 61: 839–849 (1978)Google Scholar
  88. 89.
    P. Needleman, A. Wyche and A. Raz, Platelet and blood vessel arachidonate metabolism and interactions. J. Clin. Invest., 63: 345–349 (1979)PubMedCrossRefGoogle Scholar
  89. 90.
    A. Nordoy, B. Svensson and J. C. Hoak, The inhibitory effect of human endothelial cell monolayers on platelet reactions and its inhibition by aspirin. Thromb. Res., 12: 597–608 (1978)PubMedCrossRefGoogle Scholar
  90. 91.
    Oelz, H. W. Seyberth, H. R. Knapp, B. J. Sweetman and U. A. Oates, Effects of feeding ethyl-dihomo-y-linolenate on prostaglandin biosynthesis and platelet aggregation in the rabbit. Biochim. Biophys. Acta., 431: 268–277 (1976)CrossRefGoogle Scholar
  91. 92.
    J. O’Grady and S. Moncada, Aspirin: A paradoxical effect on bleeding time. Lancet, ii: 780P (1978)Google Scholar
  92. 93.
    J. O’Grady, S. Warrington, M. J. Moti, S. Bunting, R. J. Flower, A. S. E. Fowle, E. A. Higgs and S. Moncada, Effects of intravenous prostacyclin infusions in healthy volunteers - some preliminary observations. In: Prostacyclin, J. R. Vane and S. Bergstrom, , Raven Press, New York, in press (1979)Google Scholar
  93. 94.
    T. L. Owen, I. C. Ehrhart, W. J. Weidner, J. B. Scott and F. J. Haddy, Effects of indomethacin on local blood flow regulation in canine heart and kidney. Proc. Soc. Exp. Biol. Med., 149: 871–876 (1975)PubMedGoogle Scholar
  94. 95.
    C. Pace-Asciak, Isolation, structure and biosynthesis of 6-keto-prostaglandin F1 in the rat stomach. J. Am. Chem. Soc., 98:2348–2349 (197g)Google Scholar
  95. 96.
    K. Pomerantz, A. Sintetos and P. Ramwell, The effect of prostacyclin on the human umbilical artery. Prostaglandins, 15: 1035–1044 (1978)PubMedGoogle Scholar
  96. 97.
    S. M. Rajah, S. Penny and R. Kester, Aspirin and bleeding time. Lancet, ii: 1104 (1978)Google Scholar
  97. 98.
    A. Raz, P. C. Isakson, M. S. Minkes and P. Needleman, Characterisation of a novel metabolic pathway of arachidonate in coronary arteries which generates a potent endogenous coronary vasodilator. J. Biol. Chem., 252: 1123–1126 (1977)PubMedGoogle Scholar
  98. 99.
    A. Raz, M. S. Minkes and P. Needleman, Endoperoxides and thromboxanes. Structural determinants for platelet aggregation and vasoconstriction. Biochim. Biophys. Acta., 488: 305–311 (1977)PubMedCrossRefGoogle Scholar
  99. 100.
    G. Remuzzi, A. E. Cavenaghi, G. Mecca, M. B. Donati and G. De Gaetano, Human renal cortex generates prostacyclin-like activity. Thromb. Res., 12: 363–366 (1978)PubMedCrossRefGoogle Scholar
  100. 101.
    J. P. Sackler and J. Liu, Heparin induced osteoporosis. Br. J. Radiol., 46: 548–550 (1973)PubMedCrossRefGoogle Scholar
  101. 102.
    J. A. Salmon, D. R. Smith, R. J. Flower, S. Moncada and J. R. Vane, Some characteristics of the prostacyclin synthesizing enzyme in porcine aorta, Biochim. Biophys. Acta., 523: 250–262 (1978)CrossRefGoogle Scholar
  102. 103.
    K. Schror, S. Moncada, F. B. Ubatuba, and J. R. Vane, Transformation of arachidonic acid and prostaglandin endoperoxides by the guinea-pig heart. Formation of RCS and prostacyclin. Eur. J. Pharmac., 47: 103–114 (1978)CrossRefGoogle Scholar
  103. 104.
    K. Silberbauer, H. Sinzinger and M. Winter, Prostacyclin activity in rat kidney stimulated by angiotensin II. Br. J. Exp. Path., 60: 38–44 (1979)Google Scholar
  104. 105.
    A. K. Sim and A. P. McCraw, The activity of y-linolenate and dihomo-y-linolenate methyl esters in vitro and in vivo on blood platelet function in non-human primates and in man. Thromb. Res., 10: 385–397 (1977)PubMedCrossRefGoogle Scholar
  105. 106.
    H. Sinzinger, W. Feigl and K. Silberbauer, Prostacyclin generation in atherosclerotic arteries, Lancet, ii: 469 (1979)Google Scholar
  106. 107.
    T. J. Slater, Free Radical Mechanisms in Tissue Injury, Ltd., London (1972)Google Scholar
  107. 108.
    A. Szczeklik, R. J. Gryglewski, E. Nizankowska, R. Nizankowski and J. Musial,Pulmonary and antiplatelet effects of intravenous and inhaled prostacyclin in man. Prostaglandins, 16: 654–660 (1978)Google Scholar
  108. 109.
    R. L. Tansik, D. H. Namm and H. L. White, Synthesis of prostaglandin 6-keto-Fla by cultured aortic mooth muscle cells an d stimulation of its formation in a coupled system with platelet lysates. Prostaglandins, 15: 399–408 (1978)PubMedGoogle Scholar
  109. 110.
    J. E. Tateson, S. Moncada and J. R. Vane, Effects of prostacyclin (PGX) on cyclic AMP concentrations in human platelets. Prostaglandins, 13: 389–399 (1977)PubMedGoogle Scholar
  110. 111.
    F. B. Ubatuba, S. Moncada and J. R. Vane, The effect of prostacyclin (PGI2) on platelet behaviour, thrombus formation in vivo and bleeding time. Thromb. Haem., 41: 425–434 (1979)Google Scholar
  111. 112.
    J. R. Vane, Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biol., 231: 232–235 (1971)PubMedGoogle Scholar
  112. 113.
    P. C. Weber, C. Larsson, E. Anggard, M. Hamberg, E. J. Corey, K. C. Nicolaou and B. Samuelsson, Stimulation of renin release from rabbit renal cortex by arachidonic acid and prostaglandin endoperoxides. Circ. Res., 39: 868–874 (1976)CrossRefGoogle Scholar
  113. 114.
    H. J. Weiss and V. T. Turitto, Prostacyclin (prostaglandin I2, PGI2) inhibits platelet adhesion and thrombus formation on subendothelium. Blood, 53: 244–250 (1979)PubMedGoogle Scholar
  114. 115.
    B. B. Weksler, A. J. Marcus and E. A. Jaffe, Synthesis of prostaglandin I2 (prostacyclin) by cultured human and bovine endothelial cells. Proc. Natl. Acad. Sci. USA, 74: 3922–3926 (1977)PubMedCrossRefGoogle Scholar
  115. 116.
    A. R. Wharton, K. Misono, J. Hollifield, J. C. Frolich, T. Inagami and J. A. Oates, Prostaglandins and renin release: I Stimulation of renin release from rabbit renal cortical slices by PGI2. Prostaglandins, 14: 1095–1104 (1977)Google Scholar
  116. 117.
    A. R. Wharton, M. Smigel, J. A. Oates and J. C. Frolich, Evidence for prostacyclin production in renal cortex. Prostaglandins, 13: 1021 (1977)Google Scholar
  117. 118.
    A. L. Willis, K. Cornai, D. C. Kuhn and J. Paulsrud, Dihomo-y-linolenate suppresses platelet aggregation when administered in vitro or in vivo. Prostaglandins, 8: 509–519 (1974)PubMedGoogle Scholar
  118. 119.
    T. V. Zenser, C. A. Herman, R. R. Gorman and B. B. Davis, Metabolism and action of the prostaglandin endoperoxide PGH2 in rat kidney. Biochem. Biophys. Res. Commun., 79: 357–363 (1977)PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • S. Moncada
    • 1
  • J. R. Vane
    • 1
  1. 1.Wellcome Research LaboratoriesLangley CourtBeckenham, KentUK

Personalised recommendations