Physiologische und pathophysiologische Rolle von Eikosanoiden im kardiovaskulären System unter dem Aspekt der Therapie peripherer Gefäßerkrankungen

  • H. Neuhof
Conference paper
Part of the Anaesthesiologie und Intensivmedizin Anaesthesiology and Intensive Care Medicine book series (A+I, volume 177)


Eikosanoide sind oxygenierte Derivate von mehrfach ungesättigten Fettsäuren mit einem Gerüst aus 20 C-Atomen. Zu ihnen zählen die Prostaglandine, Thromboxane, Leukotriene und die Hydroxy- und Hydroperoxyfettsäuren, die potente biologische Wirkungen ausüben und als Mediatoren an vielen Regulationsprozessen und zellulären Interaktionen beteiligt sind.


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  1. 1.
    Armstrong JM (1982) Prostaglandins: Pre-and postjunctional modulation of adrenergic nerve function. In: Herman, Vanhoutte, Denolin, Goossens (eds) Cardiovascular pharmacology of the prostaglandins. Raven, New York, p 51.Google Scholar
  2. 2.
    Baumgartner HR, Muggli R (1976) Adhesion and aggregation: Morphological demonstration and quantitation in vivo and in vitro. In: Gordon JL (ed) Platelets in biology and pathology. Elsevier, Amsterdam, p 23.Google Scholar
  3. 3.
    Belch JJF, Lowe GDO, Drummond MM, Forbes CD, Prentice CRM (1981) Prostacyclin reduces red cell deformiability. Thromb Haemost 45:189.PubMedGoogle Scholar
  4. 4.
    Borgeat P, Hamberg M, Samuelsson S (1976) Transformation of arachidonic acid and dihomo-γ-linole-nic acid by polymorphnuclear leukocytes. J Biol Chem 251:7816.PubMedGoogle Scholar
  5. 5.
    Burch JW, Stanford N, Majerus PW (1978) Inhibition of platelet prostaglandinsynthetase by oral aspirin. J Clin Invest 61:314.PubMedCrossRefGoogle Scholar
  6. 6.
    Coceani F, Olley PM, Lock JE (1980) Prostaglandins, ductus arteriosus, pulmonary circulation: Current concepts and clinical potential. Eur J Clin Pharmacol 181:75.CrossRefGoogle Scholar
  7. 7.
    Dahlén S-E, Björk J, Hedqvist P et al (1981) Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: In vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci 78:3887.PubMedCrossRefGoogle Scholar
  8. 8.
    Dyerberg J (1982) Dietary manipulation of prostaglandin synthesis: Beneficial or detrimental? In: Herman AG, Vanhoutte PM, Denolin H, Goossens A (eds) Cardiovascular pharmacology of the prostaglandins. Raven, New York, p 233.Google Scholar
  9. 9.
    Eklund AE, Eriksson G, Olsson AG (1982) A controlled study showing significant short-term effect of prostaglandin E1 in healing of ischaemic ulcers of the lower limbs in man. Prostaglandins Med 8:265.CrossRefGoogle Scholar
  10. 10.
    Fischer S, Weber PC (1984) Prostaglandin I3 is formed in vivo in man after dietary eicosapentaenoic acid. Nature 307:165.PubMedCrossRefGoogle Scholar
  11. 11.
    Flower RJ, Blackwell GJ (1976) The importance of phospholipase A2in prostaglandin biosynthesis. Biochem Pharmacol 25:285.PubMedCrossRefGoogle Scholar
  12. 12.
    Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith MJH (1980) Leukotriene B: A potent chemokinetic and aggregating substance released from polymorphnuclear leukocytes. Nature 286:264.PubMedCrossRefGoogle Scholar
  13. 13.
    Frölich JC, Rosenkranz B (1982) Role of prostaglandins in the regulation of blood pressure. In: Herman, Vanhoutte, Denolin, Goossens (eds) Cardiovascular pharmacology of the prostaglandins. Raven, New York, p 259.Google Scholar
  14. 14.
    Goetzl EJ, Gorman RR (1978) Chemotactic and chemokinetic stimulation of human eosinophil and neutrophil polymorphnuclear leucocytes by 12-L-hydroxy-5, 8, 10-heptadecatrienoic acid (HHT). J Immunol 120:526.PubMedGoogle Scholar
  15. 15.
    Goetzl EJ, Woods JM, Gorman RR (1977) Stimulation of human eosinophil and neutrophil polymorphnuclear leukocyte chemotaxis and random migration by 12-L-hydroxy-5,8,10,14-eicosatetraenoic acid. J Clin Invest 59:179.PubMedCrossRefGoogle Scholar
  16. 16.
    Gryglewski RJ, Dembinska-Kiec A, Glytkowski A, Gryglewski T (1978) Prostacyclin and thromboxane A2 biosynthesis capacities of heart, arteries and platelets at various stages of experimental artherosklerosis in rabbits. Artherosclero sis 31:385.Google Scholar
  17. 17.
    Ham EA, Egan RW, Soderman DD, Gale PH, Kuehl FA Jr (1979) Peroxidase-dependent deactivation of prostacyclin synthetase. J Biol Chem 254:2191.PubMedGoogle Scholar
  18. 18.
    Hamberg M, Hamberg G (1980) On the mechanism of the oxygenation of the arachidonic acid by human platelet lipoxygenase. Biochem Biophys Res Commun 95:1090.PubMedCrossRefGoogle Scholar
  19. 19.
    Hammarström S (1982) Biosynthesis and biological actions of prostaglandins and thromboxanes. Arch Biochem Biophys 214:431.PubMedCrossRefGoogle Scholar
  20. 20.
    Hong SL, Levine L (1976) Stimulation of prostaglandin synthesis by bradykinin and thrombin and their mechanism of action on MCS-fibroblasts. J Biol Chem 251:5814.PubMedGoogle Scholar
  21. 21.
    Hossman V, Heinen A, Auel A, FitzGerald GA (1981) A randomized, placebo-controlled trial of prostacyclin (PGI2) in peripheral arterial disease. Thromb Res 22:481.PubMedCrossRefGoogle Scholar
  22. 22.
    Hsueh W, Isakson PC, Needleman P (1977) Hormone selective lipase activation in the isolated rabbit heart. Prostaglandins 13:1073.PubMedCrossRefGoogle Scholar
  23. 23.
    Kilbom A, Wennmalm A (1977) Endogenous prostaglandins as local regulators of blood flow in man: Effect of indomethacin on reactive and functional hvperaemia. J Physiol (Lond) 257:109.Google Scholar
  24. 24.
    Lefer AM (1983) Role of prostaglandins and thromboxanes in shock states. In: Altura BM et al (eds) Basic science. Raven, New York (Handbook of shock and trauma, vol 1, p 355).Google Scholar
  25. 25.
    Lefer AM, Araki H, Okamatsu S (1981) Beneficial actions of a free radical scavenger in traumatic shock and myocardial ischemia. Circ Shock 8:273.PubMedGoogle Scholar
  26. 26.
    Lindbom L, Hedqvist P, Dahlen S-E, Lindgren JA, Arfors K-E (1982) Leukotriene B4 induces extravasation and migration of polymorphnuclear leukocytes in vivo. Acta Physiol Scand 116:105.PubMedCrossRefGoogle Scholar
  27. 27.
    Lucas A, Mitchell MD (1978) Plasma prostaglandins in pre-term neonates before and after treatment for patent ductus arteriosus. Lancet 11:130.CrossRefGoogle Scholar
  28. 28.
    Marcus AJ, Broekman MJ, Safier LB, Ullman HL, Islam N (1982) Formation of leukotrienes and other hydroxy acids during platelet-neutrophil interactions in vitro. Biochem Biophys Res Commun 109:130.PubMedCrossRefGoogle Scholar
  29. 29.
    Moncada S, Vane JR (1978) Unstable metabolites of arachidonic acid and their role in haemostasis and thrombosis. Br Med Bull 34:129.PubMedGoogle Scholar
  30. 30.
    Moncada S, Herman A, Higgs EA, Vane JR (1977) Differential formation of prostacyclin (PGX or PGI2) by layers of the arterial wall. An explanation for the antithrombotic properties of vascular endothelium. Thromb Res 11:323.PubMedCrossRefGoogle Scholar
  31. 31.
    Needleman P, Moneada S, Bunting S, Vane JR, Hamberg M, Samuelsson B (1976) Identification of an enzyme in platelet microsomes which generates thromboxane A2 from prostaglandin endoperoxides. Nature 261:558.PubMedCrossRefGoogle Scholar
  32. 32.
    Neuhof H, Noak A, Hoffmann C, Seeger W (to be published) Thromboxane mediated pulmonary vasoconstriction in rabbits induced by acute alveolar hypoxia. 2. Internationales Prostaglandin-Sympo-sium, Erlangen 1984..Google Scholar
  33. 33.
    Neuhof H, Seeger W, Wolf HRD, Hall J, Neumann C, Srampical B (in press) Acute increase in pulmonary vascular resistance induced by circulating fibrin monomers, mediated by pulmonary thromboxan A2 generation. Eur J Respir Dis.Google Scholar
  34. 34.
    Oettinger W, Seifert J (1982) Pathophysiologische Bedeutung der Prostanoide im septischen Schock. Fortschr Med 100:2169.PubMedGoogle Scholar
  35. 35.
    Ogletree M, Brigham KL (1979) Indomethacin augments endotoxin induced increased lung vascular permeability in sheep. Rev Respir Dis 119:383.Google Scholar
  36. 36.
    Pardy BJ, Hoare MC, Eastcott HHG (1982) Prostaglandin E1 in severe Raynaud’s phenomenon. Surgery 92:953.PubMedGoogle Scholar
  37. 37.
    Platshon LF, Kaliner M (1978) The effects of the immunologic release of histamine upon human lung cyclic nucleotide levels and prostaglandin generation. J Clin Invest 62:1113.PubMedCrossRefGoogle Scholar
  38. 38.
    Polley MJ, Nachman RL, Weksler BB (1981) Human complement in the arachidonic acid transformation pathway in platelets. J Exp Med 153:257.PubMedCrossRefGoogle Scholar
  39. 39.
    Rasmussen H, Lake W, Allen JE (1975) The effect of catecholamines and prostaglandins upon human and rat erythrocytes. Biochim Biophys Acta 411:63.PubMedGoogle Scholar
  40. 40.
    Rittenhouse-Simmons S, Deykin D (1981) Release and metabolism of arachidonate in human platelets. Thromb Haemost 41:349.Google Scholar
  41. 41.
    Robertson RP (1983) Prostaglandins, glucose, homeostasis and diabetes mellitus. Annu Rev Med 34:1.PubMedCrossRefGoogle Scholar
  42. 42.
    Ross R, Glomset JA (1976) The pathogenesis of atherosclerosis. N Engl J Med 295:420.PubMedCrossRefGoogle Scholar
  43. 43.
    Sacks T, Moldow CF, Craddock PR et al (1978) Oxygen radicals mediate endothelial cell damage by complementstimulated granulocytes. J Clin Invest 61:1161.PubMedCrossRefGoogle Scholar
  44. 44.
    Samuelsson B, Borgeat P, Hammarström S, Murphy RC (1980) Leucotrienes: A new group of biologically active compounds. Adv Prostaglandin Thromboxane Leukotriene Res 6:1.Google Scholar
  45. 45.
    Schöber JG, Keller M, Mocellin R, Schumacher G, Bühlmeyer K (1980) Indications and pharmacological effects of therapy with prostaglandin E1 in the newborn. Adv Prostaglandin Thromboxane Leukotriene Res 7:905.Google Scholar
  46. 46.
    Schoenberg MH, Younes M, Haglund U et al (1984) The participation of the hypoxanthin-xanthin oxidase system in the generation of free radicals after intestinal ischemia. In: Bors W, Saran M, Tait D (eds) Oxygen radicals in chemistry and biology. de Gruyter, Berlin, p 851.CrossRefGoogle Scholar
  47. 47.
    Schoene NW, Facono JM (1975) Stimulation of platelet phospholipase A2 activity by aggregating agents. Fed Proc 34:257.Google Scholar
  48. 48.
    Schrör K (1982) Bedeutung von Prostaglandinen und anderen Eikosanoiden für das Verhalten der MikroZirkulation beim Schock. Hämostasiologie 2:73.Google Scholar
  49. 49.
    Schrör K (1984) Prostagland ine und verwandte Verbindungen. Thieme, Stuttgart.Google Scholar
  50. 50.
    Seeger W, Neuhof H, Graubert E, Wolf H, Róka L (1982) Comparative influence of the Ca-ionophore A23187, bradykinin, kallidin and eledoisin on the rabbit pulmonary vasculature with special reference to arachidonate metabolism. Adv Exp Med Biol 156:533.Google Scholar
  51. 51.
    Seeger W, Wolf H, Stähler G, Neuhof H, Róka L (1982) Increased pulmonary vascular resistance and permeability due to arachidonate metabolism in isolated rabbit lungs. Prostaglandins 23:157.PubMedCrossRefGoogle Scholar
  52. 52.
    Serhan CN, Radin A, Smolen JE, Korchak H, Samuelsson B, Weissmann G (1982) Leukotriene B4 is a complete secretagogue in human neutrophils: A kinetic analysis. Biochem Biophys Res Commun 107:1006.PubMedCrossRefGoogle Scholar
  53. 53.
    Serneri GCN, Masotti G, Poggesi L, Galanti G (1980) Release of prostacyclin into the bloodstream in humans after local blood flow changes. Adv Prostaglandin Thromboxane Leukotriene Res 7:715.Google Scholar
  54. 54.
    Sinzinger H, Silberbauer K, Winter M (1979) Effects of experimental atherosclerosis on prostacyclin (PGI2) generation in arteries of the miniature swine. Artery 5:448.Google Scholar
  55. 55.
    Spagnuolo PJ, Ellner JJ, Hassid A, Dunn MJ (1980) Thromboxane A2 mediates augmented polymorphnuclear leukocyte adhesiveness. J Clin Invest 66:406.PubMedCrossRefGoogle Scholar
  56. 56.
    Stimler NP, Brocklehurst WE, Bloor CM, Hugli TE (1980) Complement anaphylatoxin C5a stimulates release of SRS-A-like activity from guinea-pig lung fragments. J Pharm Pharmacol 32:804.PubMedCrossRefGoogle Scholar
  57. 57.
    Szeczeklik A, Skawinski S, Gluszko P, Nizankowski R, Szczeklik J, Gryglewski RJ (1979) Successful therapy of advanced arteriosclerosis obliterans with prostacyclin. Lancet V:1111.CrossRefGoogle Scholar
  58. 58.
    Szczeklik J, Dubiel JS, Mysik M, Pyzik Z, Krol R, Horzela T (1978) Effects of prostaglandin E1 on pulmonary circulation in patients with pulmonary hypertension. Br Heart J 40:1397.PubMedCrossRefGoogle Scholar
  59. 59.
    Thomas G, Rao PWP (1979) Leukocyte migration and prostaglandin E1. J Pharm Pharmacol 31:789.PubMedCrossRefGoogle Scholar
  60. 60.
    Watkins WD, Peterson MB, Crone RK, Shannon DC, Levine L (1980) Prostacyclin and prostaglandin E1 for severe idiopathic pulmonary artery hypertension. Lancet XVII: 1083.CrossRefGoogle Scholar
  61. 61.
    Weismann G, Smolen JE, Korchak HM (1980) Release of inflammatory mediators from stimulated neutrophils. N Engl J Med 303:27.CrossRefGoogle Scholar
  62. 62.
    Weiss JW, Drazen JM, Coles N, McFadden ER Jr, Austen KF (1982) Bronchoconstrictor effect of leukotriene C in humans. Science 216:196.PubMedCrossRefGoogle Scholar
  63. 63.
    Weksler BB, Levy CW, Jaffe EA (1978) Stimulation of endothelial cell prostacyclin production by thrombin, trypsin and the ionophore A23187. J Clin Invest 62:923.PubMedCrossRefGoogle Scholar
  64. 64.
    Weksler BB, Knapp JM, Jaffe EA (1979) Prostacyclin (PGI2) synthesized by cultured endothelial cells modulates polymorphnuclear leukocyte function. Blood [Suppl 1] 50:287.Google Scholar
  65. 65.
    Wennmalm A (1978) Effects of nicotine on cardiac prostaglandin and platelet thromboxane synthesis. Br J Pharmacol 64:559.PubMedGoogle Scholar
  66. 66.
    Wennmalm A (1979) Cigarette smoking, prostaglandins and reactive hyperemia. Prostaglandins Med 3:321..PubMedGoogle Scholar
  67. 67.
    Wolf H, Seeger W, Suttorp N, Neuhof H (1981) Experimental results in the prevention of RDS with α-tocopherol. Prog Respir Res 15:308.Google Scholar

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  • H. Neuhof

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