Advertisement

The Molecular, Biochemical and Human Pharmacology of Thromboxane A2 in Renal Disease

  • Garret A. FitzGerald
  • Rosemary Murray
  • Patricia Price
  • Francesca Catella
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 259)

Abstract

Arachidonic acid is a constituent of the phospholipid domain of biological membranes. Activation of phospholipases results in its release into the intracellular milieu where it is subject to metabolism to biologically active compounds. In most cell types, including the platelet (1), the predominant enzyme involved in catalyzing arachidonate release is phospholipase A2 rather than phospholipase C (2). It has recently been shown that arachidonate may be subject to direct oxygenation within the cell membrane (3); the biological role of this process remains speculative.

Keywords

Renal Blood Flow Human Platelet Thrombotic Thrombocytopenic Purpura Thromboxane Synthesis Thromboxane Production 
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.
    P.W. Majerus, S.M. Prescott, S.L. Hofmann, E.J. Neufeld, D.B. Wilson, Uptake and release of arachidonate by platelets, in: “Advances in Prostaglandin, Thromboxane, and Leukotriene Research,” Vol. 11, B. Samuelsson, R. Paoletti, and P. Ramwell, eds., Raven Press, New York, pp. 45–52 (1983).Google Scholar
  2. 2.
    J. Bryan Smith, C. Dangelmaier, G. Mauco, Quantitation of arachidonate released during the platelet phosphatidylinositol response to thrombin, in: “Prostaglandins, Leukotrienes, and Lipoxins. Biochemistry, Mechanism of Action, and Clinical Applications,” J.M. Bailey, ed., Plenum Press, New York, pp. 205–211 (1985).CrossRefGoogle Scholar
  3. 3.
    A.R. Brash, A.T. Porter, R.L. Maas, Investigation of the selectivity of hydrogen abstraction in the nonenzymatic formation of hydroxyeicosate-traenoic acids and leukotrienes by autoxidation, J. Biol. Chem. 7: 4210–4216 (1986).Google Scholar
  4. 4.
    G.A. FitzGerald, Prostaglandins and related compounds, .in: “Cecil Loeb Textbook of Medicine,” L.H. Smith, Jr., ed., W.B. Saunders, Philadelphia, (in press) (1988).Google Scholar
  5. 5.
    B. Samuelsson, Leukotrienes: mediators of immediate hypersensitivity and inflammation, Science 220:568–574 (1983).CrossRefPubMedGoogle Scholar
  6. 6.
    C.N. Serhan, M. Hamberg, B. Samuelsson, Lipoxins: a novel series of biologically active compounds, in: “Prostaglandins, Leukotrienes and Lipoxins. Biochemistry, Mechanism of Action, and Clinical Applications,” J.M. Bailey, ed., Plenum Press, New York, pp. 3–16 (1985).CrossRefGoogle Scholar
  7. 7.
    P. Needleman, J. Turk, B.A. Jakshik et al., Arachidonic acid metabolism, Ann. Rev. Biochem. 55:69–82 (1986).CrossRefPubMedGoogle Scholar
  8. 8.
    J.R. Vane, Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs, Nature (New Biology) 231:232–235 (1971).Google Scholar
  9. 9.
    J.B. Smith, A.L. Willis, Aspirin selectivity inhibits prostaglandin production in human platelets, Nature (New Biology) 231:235–237 (1971).Google Scholar
  10. 10.
    J.W. Burch, N.L. Baenziger, N. Stanford, P.W. Majerus, Sensitivity of fatty acid cyclooxygenase from human aorta to acetylation by aspirin, Proc. Natl. Acad. Sci. USA 75:5181–5184 (1978).CrossRefPubMedGoogle Scholar
  11. 11.
    H.D. Lewis, J.W. Davis, D.G. Archibald et al., Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina, N. Engl. J. Med. 309:396–403 (1983).CrossRefPubMedGoogle Scholar
  12. 12.
    J.A. Cairns, M. Gent, J. Singer et al., Aspirin, sulfinpyrazone, or both in unstable angina: Results of a Canadian multicentre trial, N. Engl. J. Med. 313:1369–1374 (1985).CrossRefPubMedGoogle Scholar
  13. 13.
    L.J. Roberts, II, R.A. Lewis, K.F. Austen, J.A. Oates, Prostaglandin, thromboxane, and 12-hydroxy-5,8,10,14-eicosatetraenoic acid production by ionophore-stimulated rat serosal mast cells, Biochim. Biophys. Acta. 575:185–192 (1979).CrossRefPubMedGoogle Scholar
  14. 14.
    S.R. Bunting, R.J. Gryglewski, S. Moncada et al., Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac arteries and inhibits platelet aggregation, Prostaglandins 12:897–904 (1976).PubMedGoogle Scholar
  15. 15.
    M.E. Gerritsen and CD. Cheli, Arachidonic acid and prostaglandin endoperoxide metabolism in isolated rabbit and coronary microvessels and isolated and cultivated coronary microvessel endothelial cells, J. Clin. Invest. 72:1658–1671 (1984).CrossRefGoogle Scholar
  16. 16.
    I.F. Charo, S. Shak, M.A. Karasek, P.M. Davison, I.M. Goldstein, Prostaglandin I2 is not a major metabolite of arachidonic acid in cultured endothelial cells from human foreskin microvessels, J. Clin. Invest. 74:914–919 (1984).CrossRefPubMedGoogle Scholar
  17. 17.
    M. Hamberg, J. Svensson, B. Samuelsson, Thromboxanes — a new group of biologically active compounds derived from prostaglandin endoperoxides, Proc. Natl. Acad. Sci. USA 72:2994–2998 (1975).CrossRefPubMedGoogle Scholar
  18. 18.
    G.A. FitzGerald, C. Healy, J. Daugherty, Thromboxane A2 biosynthesis inhuman disease, Fed. Proc. 46:154–158 (1987).PubMedGoogle Scholar
  19. 19.
    J.R. Coleman, P. Humphrey, I. Kennedy, P. Lumley, Prostanoid receptors — the development of a working classification, Trends Pharmacol. Sci. 59:303–306 (1984).CrossRefGoogle Scholar
  20. 20.
    D.E. Mais, R.M. Burch, D.L. Saussy, P.J. Kochel, P.V. Halushka, Binding of a thromboxane A2/prostaglandin H2 receptor antagonist to washed human platelets, J. Pharm. Exp. Ther. 235:729–734 (1985).Google Scholar
  21. 21.
    N. Liel, D.E. Mais, P.V. Halushka, Binding of a thromboxane A2/prostaglandin H2 agonist [3H]U46619 to washed human platelets, Prostaglandins 33:789–797 (1987).PubMedGoogle Scholar
  22. 22.
    P.V. Halushka, J. MacDermot, D. Knapp, T. Eller, D. Saussy, D. Mais, I. Blair, C. Dollery, A novel approach for the study of thromboxane A2 125 and prostaglandin H2 receptors using an 125I-labelled ligand, Biochem. Pharmacol. 34:1165–1170 (1985).CrossRefPubMedGoogle Scholar
  23. 23.
    D. Mais, D. Knapp, K. Ballard, P. Haiushka, N. Hamanaka, Synthesis of thromboxane receptor antagonists with the potential to radiolabel with 125I, Tetrahedron Lett. 25:4207–4210 (1984).CrossRefGoogle Scholar
  24. 24.
    G.W. Dorn, II, D. Sens, A. Chaikhouni, D. Mais, P.V. Halushka, Cultured human vascular smooth muscle cells with functional thromboxane A2 receptors: Measurement of U46619-induced 45Calcium efflux, Circulation Res. 60:952–956 (1988).CrossRefGoogle Scholar
  25. 25.
    P. Mené and M.J. Dunn, Contractile effects of TxA2 and endoperoxide analogues on cultured rat glomerular mesangial cells, Am. J. Physiol. 251:F1029–F1035 (1986).PubMedGoogle Scholar
  26. 26.
    K. Hanasaki, K. Nakano, H. Kasai, H. Kurihara, H. Arita, Identification of thromboxane A2 receptors in cultured vascular endothelial cells of rat aorta, Biochem. Biophys. Res. Comm. 151:1352–1357 (1988).CrossRefPubMedGoogle Scholar
  27. 27.
    W.L. Smith and A.G. Garcia-Perez, A two-receptor model for the mechanism of action of prostaglandins in the renal collecting tubule, in: “Prostaglandins, Leukotrienes, and Lipoxins. Biochemistry, Mechanism of Action, and Clinical Applications”, J.M. Bailey, ed., Plenum Press, New York, pp. 35–45 (1985).CrossRefGoogle Scholar
  28. 28.
    D.E. Mais, D.L. Saussy, Jr., A. Chaikhouni, P.J. Kochel, D.R. Knapp, N. Hamanaka, P.V. Halushka, Pharmacologic characterization of human and canine thromboxane A2/prostaglandin H2 receptors in platelets and blood vessels: Evidence for different receptors, J. Pharm. Exp. Ther. 233:418–424 (1985).Google Scholar
  29. 29.
    D.L. Saussy, Jr., D.E. Mais, R.M. Burch, P.V. Halushka, Identification of a putative thromboxane A2/prostaglandin H2 receptor in human platelet membranes, J. Biol. Chem. 261:3025–3029 (1986).PubMedGoogle Scholar
  30. 30.
    D.E. Mais and P.V. Halushka, Synthesis of an [125I]-Azido photoaffinity probe for the human platelet thromboxane A2/prostaglandin H2 receptor, J. Labelled Compounds and Radiopharmaceuticals. (in press) (1988).Google Scholar
  31. 31.
    P. Mayeux and P. Halushka, Discovery of a functional thromboxane (Tx) A2/prostaglandin (PG) H2 receptor in the human erythroleukemia (HEL) cells, Fed. Proc. 2:A1050 (1988).Google Scholar
  32. 32.
    P. Mené, M. Simonson and M.J. Dunn, Prostaglandins, thromboxane and leukotrienes in the control of mesangial function, in: “Renal Eicosanoids”, M.J. Dunn, ed., Plenum Press, New York (1989).Google Scholar
  33. 33.
    S.S. Bhagwat, P.R. Hamann, W.E. Still, S. Bunting, F.A. Fitzpatrick, Synthesis and structure of the platelet aggregation factor, thromboxane A2, Nature 315:511–513 (1985).CrossRefPubMedGoogle Scholar
  34. 34.
    G.A. FitzGerald, I.A.G. Reilly, A.K. Pedersen, The biochemical pharmacology of thromboxane synthase inhibition in man, Circulation 72: 1194–1201 (1985).CrossRefPubMedGoogle Scholar
  35. 35.
    J.B. Smyth, A. Yanagisawa, R. Zipkin, A.M. Lefer, Constriction of cat coronary arteries by synthetic thromboxane A2 and its antagonism, Prostaglandins 33:777–782 (1987).Google Scholar
  36. 36.
    A.M. Lefer, E.F. Smith, III, H. Araki, J.R. Smith, D. Aharony, D.A. Claremon, R.I. Magolda, K.C. Nicolaou, Dissociation of vasoconstrictor and platelet aggregatory activities of thromboxane by carbocyclic thromboxane A2, a stable analog of thromboxane A2, Proc. Natl. Acad. Sci. USA 77:1706–1710 (1980).CrossRefPubMedGoogle Scholar
  37. 37.
    R.A. Armstrong, R.L. Jones, V. Peesapati, S.G. Will, N.H. Wilson, Competitive antagonism at thromboxane receptors in human platelets, Br. J. Pharmac. 84:595–607 (1985).CrossRefGoogle Scholar
  38. 38.
    F.A. Fitzpatrick and R.R. Gorman, Regulatory role of cyclic adenosin 3′,5′-monophosphate on the platelet cyclooxygenase and platelet function, Biochim. Biophys. Acta. 582:44–58 (1979).CrossRefPubMedGoogle Scholar
  39. 39.
    P.V. Avdonin, I.V. Svitina-Ulitina, V.L. Leytin, V.A. Tkachuk, Interaction of stable prostaglandin endoperoxide analogs U46619 and U44069 with human platelet membranes: Coupling of receptors with high-affinity GTPase and adenylate cyclase, Thromb. Res. 40:101–112 (1985).CrossRefPubMedGoogle Scholar
  40. 40.
    K.C. Nicolaou, R.L. Magolda, J.B. Smith, J.B. Aharony, E.F. Smith, A.M. Lefer, Synthesis and biological properties of pinane-thromboxane A2, a selective inhibitor of coronary artery constriction, platelet aggregation, and thromboxane formation, Proc. Natl. Acad. Sci. USA 76:2566–2570 (1979).CrossRefPubMedGoogle Scholar
  41. 41.
    R.A. Armstrong, R.L. Jones, J. MacDermot, N.H. Wilson, Prostaglandin endoperoxide analogues which are both thromboxane receptor antagonists and prostacyclin mimetics, Br. J. Pharmac. 87:543–551 (1986).CrossRefGoogle Scholar
  42. 42.
    J.P. Rybicki, D.L. Venton, G.C. Breton, The thromboxane antagonist, 13-azaprostanoic acid, inhibits arachidonic acid-induced Ca2+ release from isolated platelet membrane vesicles, Biochim. Biophys. Acta. 751:66–73 (1983).CrossRefPubMedGoogle Scholar
  43. 43.
    K. Yasuhiro, J. Yamanish, Y. Furuta, K. Kaibuchi, Y. Takai, H. Fukuzaki, Elevation of cytoplasmic free calcium concentration by stable thromboxane A2 analogue in human platelets, Biochem. Biophys. Res. Comm. 117:663–669 (1983).CrossRefGoogle Scholar
  44. 44.
    R.M. Lyons, N. Stanfrod, P.W. Majerus, Thrombin-induced protein phosphorylation in human platelets, J. Clin. Invest. 56:924–936 (1975).CrossRefPubMedGoogle Scholar
  45. 45.
    K. Sano, Y. Takai, J. Yamanishi, Y. Nishizuka, A role of calcium-activated phospholipid-dependent protein kinase in human platelet activation. Comparison of thrombin and collagen actions, J. Biol. Chem. 258:2010–2013 (1983).PubMedGoogle Scholar
  46. 46.
    W. Siess, B. Boehlig, P.C. Weber, E.G. Lapetina, Prostaglandin endoperoxide analogues stimulate phospholipase C and protein phosphorylation during platelet shape change, Blood 65:1141–1148 (1985).PubMedGoogle Scholar
  47. 47.
    Y. Kawahara, H. Fukuzaki, K. Kaibuchi, T. Tsuda, M. Hoshijima, A.Y. Takai, Activation of protein kinase C by the action of 9,11-epithio -11,12-methano-thromboxane A2 (STA2), a stable analogue of thromboxane A2, in human platelets, Throm. Res. 41:811–818 (1986).CrossRefGoogle Scholar
  48. 48.
    O.V. Miller, R.A. Johnson, R.R. Gorman, Inhibition of PGE1-stimulated cAMP accumulation in human platelets by thromboxane A2, Prostaglandins 13:599–609 (1977).PubMedGoogle Scholar
  49. 49.
    O.V. Miller and R.R. Gorman, Modulation of platelet cyclic nucleotide content by PGE1 and the prostaglandin endoperoxide PGG2, J. Cyclic Nucleotide Res. 2:79–87 (1976).PubMedGoogle Scholar
  50. 50.
    J. Nowak and G.A. FitzGerald, Reorientation of prostaglandin endoperoxide metabolism at the platelet-vascular interface in man, Clin. Res. 35:580A (1987).Google Scholar
  51. 51.
    L.G. Carmo, M. Hatmi, D. Rotilio, B.B. Vargaftig, Platelet desensitization induced by arachidonic acid is not due to cyclo-oxygenase inac-tivation and involves the endoperoxide receptor, Br. J. Pharmac. 85: 849–859 (1985).CrossRefGoogle Scholar
  52. 52.
    R. Murray, F. Catella, G.A. FitzGerald, Desensitization of TxA2/PGH2 receptor in human platelets, Circulation 76:iv–483 (1987).Google Scholar
  53. 53.
    R. Murray and G.A. FitzGerald, Regulation of thromboxane receptor activation in human platelets, Proc. Natl. Acad. Sci. (USA) 86:124–128 (1989).CrossRefGoogle Scholar
  54. 54.
    D.R. Sibley, R.H. Strasser, M.G. Caron, R.J. Lefkowitz, Homologous desensitization of adenylate cyclase is associated with phosphorylation of the ß-adrenergic receptor, J. Biol. Chem. 260:3883–3886 (1985).PubMedGoogle Scholar
  55. 55.
    L.F. Brass, C.C. Shaller, E.J. Belmonte, Inositol 1,4,5-triphosphate induced granule secretion in platelets. Evidence that the activation of phospholipase C mediated by platelet thromboxane receptors involves a guanine nucleotide binding protein-dependent mechanism distinct from that of thrombin, J. Clin. Invest. 79:1269–1275 (1987).CrossRefPubMedGoogle Scholar
  56. 56.
    L.J. Roberts, II, B.J. Sweetman, J.A. Oates, Metabolism of thromboxane B2 in man: Identification of twenty urinary metabolites, J. Biol. Chem. 256:8384–8393 (1981).PubMedGoogle Scholar
  57. 57.
    J.L. Lawson, A.R. Brash, J. Doran, G.A. FitzGerald, Measurement of uri- nary 2,3-dinor-thromboxane B2 and thromboxane B2 using bonded-phase phenylboronic acid columns and capillary gas chromatography-negative-ion chemical ionization mass spectrometry, Analyt. Biochem. 150:463–470 (1985).CrossRefPubMedGoogle Scholar
  58. 58.
    J. Lawson, C. Patrono, G. Ciabattoni, G.A. FitzGerald, Long-lived enzymatic metabolites of thromboxane B2 in human circulation, Analytical Biochem. 155:198–205 (1986).CrossRefGoogle Scholar
  59. 59.
    F. Catella and G.A. FitzGerald, Paired analysis of urinary thromboxane B2 metabolites in humans, Throm. Res. 47:647–656 (1987).CrossRefGoogle Scholar
  60. 60.
    G.A. FitzGerald, A.K. Pedersen, C. Patrono, Analysis of prostacyclin and thromboxane A2 biosynthesis in cardiovascular disease, (Editorial), Circulation 67:1174–1177 (1983).CrossRefPubMedGoogle Scholar
  61. 61.
    F. Catella, D. Healy, J. Lawson, G.A. FitzGerald, 11-dehydro-thromboxane B2: An index of thromboxane formation in the human circulation, Proc. Natl. Acad. Sci. 83:5861–5865 (1986).CrossRefPubMedGoogle Scholar
  62. 62.
    C. Patrono, G. Ciabattoni, F. Pugliese, A. Pierucci, I.A. Blair, G.A. FitzGerald, Estimated rate of thromboxane secretion into the circulation of normal man, J. Clin. Invest. 77:590–594 (1986).CrossRefPubMedGoogle Scholar
  63. 63.
    E. Granström, P. Westlund, M. Kumiin, A. Nordenstrom, Measurement of thromboxane production in vivo: Metabolic and analytical aspects, Adv. Prostaglandin. Thromboxane and Leukotriene Res. 15:67–70 (1985).Google Scholar
  64. 64.
    M. Kumiin and E. Granstrom, Radioimmunoassay for 11-dehydro-TxB2: A method for monitoring thromboxane production in vivo, Prostaglandins 32:741–767 (1986).Google Scholar
  65. 65.
    G. Ciabattoni, J. Maclouf, F. Catella, G.A. FitzGerald, C. Patrono, Radioimmunoassay of 11-dehydro-thromboxane B2 in human plasma and urine, Biochem. Biophys. Acta. 918:293–297 (1987).CrossRefPubMedGoogle Scholar
  66. 66.
    I.A.G. Reilly, J. Doran, B. Smith, G.A. FitzGerald, Increased thromboxane biosynthesis in a human model of platelet activation: Biochemical and functional consequences of selective inhibition of thromboxane synthase, Circulation 73:1300–1309 (1986).CrossRefPubMedGoogle Scholar
  67. 67.
    I.A.G. Reilly, L. Roy, G.A. FitzGerald, Thromboxane biosynthesis is increased in systemic sclerosis with Raynaud’s phenomenon, Br. Med. J. 292:1087–1089 (1986).CrossRefGoogle Scholar
  68. 68.
    D.J. Fitzgerald, L. Roy, F. Catella, G.A. FitzGerald, Platelet activation in unstable coronary disease, N. Engl. J. Med. 315:983–989 (1986).CrossRefPubMedGoogle Scholar
  69. 69.
    D.J. Fitzgerald, F. Catella, L. Roy, G.A. FitzGerald, Marked platelet activation in vivo following intravenous streptokinase in acute myocardial infarction, Circulation 77:142–150 (1988).CrossRefPubMedGoogle Scholar
  70. 70.
    D.M. Kerins, L. Roy, G.A. FitzGerald, D.J. Fitzgerald, Evidence of platelet activation during coronary thrombolysis with tissue plasminogen activator in man, Clin. Res. 36:4A (1988).Google Scholar
  71. 71.
    ISIS Collaborative Group, Results of a large randomized trial of intravenous streptokinase and oral aspirin in acute myocardial infarction, JACC 11:332A (1988).Google Scholar
  72. 72.
    G.A. FitzGerald and D.J. Fitzgerald, Modulation of thromboxane A2 formation in coronary thrombosis and thrombolysis, JACC (in press) (1988).Google Scholar
  73. 73.
    C. Patrono, G. Ciabattoni, P. Patrignani, P. Filabozzi, E. Pinca, M.A. Satta, D. Van Dorne, G.A. Cinotti, F. Pugliese, A. Pierucci, B.M. Simonetti, Evidence for a renal origin of urinary thromboxane B2 in health and disease, in: “Advances in Prostaglandin, Thromboxane, and Leukotriene Research,” Vol. II, B. Samuelsson, R. Paoletti and P. Ramwell, eds., Raven Press, New York, pp. 493–498 (1983).Google Scholar
  74. 74.
    V.E. Kelley, S. Sneve, S. Musinski, Increased renal thromboxane production in murine lupus nephritis, J. Clin. Invest. 77:252–259 (1986).CrossRefPubMedGoogle Scholar
  75. 75.
    C. Patrono, G. Ciabattoni, G. Remuzzi et al., Functional significance of renal prostacyclin and thromboxane A2 production in patients with systemic lupus erythematosus, J. Clin. Invest. 76:1011–1018 (1985).CrossRefPubMedGoogle Scholar
  76. 76.
    T.M. Coffman, D.R. Carr, W.E. Varger, P.E. Klotman, Evidence that renal prostaglandin and thromboxane production is stimulated in chronic cyclosporin nephrotoxicity, Transplantation 43:282–285 (1987).CrossRefPubMedGoogle Scholar
  77. 77.
    A.R. Morrison, K. Nishikawa, P. Needleman, Thromboxane A2 biosynthesis in the ureter obstructed isolated perfused kidney of the rabbit, J. Pharmacol. Exp. Ther. 205:1–8 (1978).PubMedGoogle Scholar
  78. 78.
    J. Benabe, S. Klahr, M.D. Hoffman et al., Production of thromboxane A2 by the kidney in glycerol-induced acute renal failure, Prostaglandins 19:333–367 (1980).PubMedGoogle Scholar
  79. 79.
    E.A. Lianos, G.A. Andres, M.J. Dunn, Glomerular prostaglandin and thromboxane synthesis in rat nephrotoxic serum nephritis, J. Clin. Invest. 72:1439–1448 (1983).CrossRefPubMedGoogle Scholar
  80. 80.
    R. Zipser, S. Myers, P. Needleman, Exaggerated prostaglandin and thromboxane synthesis in the renal vein-constricted rabbit, Circ. Res. 47: 231–237 (1980).CrossRefPubMedGoogle Scholar
  81. 81.
    M.L. Purkerson, J.H. Joist, J. Yates, A. Valdes, A. Morrison, S. Klahr, Inhibition of thromboxane synthesis ameliorates the progressive kidney disease of rats with subtotal renal ablation, Proc. Natl. Acad. Sci. USA 82:193–197 (1985).CrossRefPubMedGoogle Scholar
  82. 82.
    C. Patrono and A. Pierucci, Renal effects of nonsteroidal anti-inflammatory drugs in chronic glomerular disease, Am. J. Med. 81 (Suppl.2B): 71–83 (1986).CrossRefPubMedGoogle Scholar
  83. 83.
    D. Schlondorff, Renal prostaglandin synthesis. Sites of production and specific actions of prostaglandins, Am. J. Med. 81:1–11 (1986).CrossRefPubMedGoogle Scholar
  84. 84.
    L. Scharschmidt, M. Simonson, M.J. Dunn, Glomerular prostaglandins, angiotensin II, and nonsteroidal anti-inflammatory drugs, Am. J. Med. 81:31–42 (1986).CrossRefGoogle Scholar
  85. 85.
    D. Schwartz, K. DeSchryver-Kecskemeti, P. Needleman, Renal arachidonic acid metabolism and cellular changes in the rabbit renal vein-constricted kidney: Inflammation as a common process in renal injury models, Prostaglandins 27:605–613 (1984).PubMedGoogle Scholar
  86. 86.
    M.L. Foegh, B. Khirabadi, P.W. Ramwell, Prolongation of experimental cardiac allograft survival with thromboxane-related drugs, Transplantation 40:124–129 (1985).CrossRefPubMedGoogle Scholar
  87. 87.
    T.M. Coffman, W.E. Yarger, P.E. Klotman, Functional role of thromboxane production by acutely rejecting renal allografts in rats, J. Clin. Invest. 75:1242–1248 (1985).CrossRefPubMedGoogle Scholar
  88. 88.
    N.L. Baenziger, M.J. Dillender, P.W. Majerus, Cultured human skin fibroblasts and arterial cells produce a labile platelet inhibitory prostaglandin, Biochem. Biophys. Res. Comm. 78:294–301 (1977).CrossRefPubMedGoogle Scholar
  89. 89.
    J.W. Burch, N.L. Baenziger, N. Stanford, P.W. Majerus, Sensitivity of fatty acid cyclooxygenase from human aorta to acetylation by aspirin, Proc. Natl. Acad. Sci. USA 75:5181–5184 (1978).CrossRefPubMedGoogle Scholar
  90. 90.
    R.J. Sebaldt, J.A. Oates, G.A. FitzGerald, Eicosanoid biosynthesis and leukotriene B4 release during steroid administration in man, Clin. Res. 35:387A (1987).Google Scholar
  91. 91.
    R.J. Sebaldt, J.R. Sheller, J.A. Oates, G.A. FitzGerald, Effects of high-dose glucocorticosteroid administration on eicosanoid biosynthesis by human alveolar macrophages, Clin. Res. 2 569A (1988).Google Scholar
  92. 92.
    S. Fischer, A. Vischer, V. Preac-Mursic, P.C. Weber, Dietary docosahexaenoic acid is retroconverted in man to eicosapentaenoic acid, which can be quickly transformed to prostaglandin I3, Prostaglandins 34: 367–375 (1987).PubMedGoogle Scholar
  93. 93.
    H.R. Knapp, I.A.G. Reilly, P. Alessandrini, G.A. FitzGerald, In vivo indexes of platelet and vascular function during fish-oil administration in patients with atherosclerosis, N. Engl. J. Med. 314:937–942 (1986).CrossRefPubMedGoogle Scholar
  94. 94.
    P. Needleman, A. Raz, M.S. Minkes, J.A. Ferrendelli, H. Sprecher, Triene prostaglandins: prostacyclin and thromboxane biosynthesis and unique biological properties, Proc. Natl. Acad. Sci. USA 176:944–948 (1979).CrossRefGoogle Scholar
  95. 95.
    A. Leaf and P.C. Weber, Cardiovascular effects of n-3 fatty acids, N. Engl. J. Med. 318:549–556 (1988).CrossRefPubMedGoogle Scholar
  96. 96.
    I.A.G. Reilly and G.A. FitzGerald, Inhibition of thromboxane formation in vivo and ex vivo: Implications for therapy with platelet inhibitory drugs, Blood 69:180–186 (1987).PubMedGoogle Scholar
  97. 97.
    G.A. Braden, D.J. Fitzgerald, H.R. Knapp, G.A. FitzGerald, Increased thromboxane (Tx)A2 biosynthesis during coronary thrombosis and thrombolysis with n-3 fatty acid (FA) supplementation, Circulation 78:11–120 (1988).Google Scholar
  98. 98.
    D.M. Clive and J.S. Stoff, Renal syndromes associated with nonsteroidal anti-inflammatory drugs, N. Engl. J. Med. 310:563–572 (1984).CrossRefPubMedGoogle Scholar
  99. 99.
    J.R. Sedor, E.W. Davidson, M.J. Dunn, Effects of nonsteroidal antiinflammatory drugs in healthy subjects, Am. J. Med. 81(Suppl. 2B): 59–70 (1986).Google Scholar
  100. 100.
    J.W. Burch, N. Stanford, P.W. Majerus, Inhibition of platelet prostaglandin synthetase by oral aspirin, J. Clin. Invest. 61:314–319 (1978).CrossRefPubMedGoogle Scholar
  101. 101.
    P. Patrignani, P. Filabozzi, C. Patrono, Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects, J. Clin. Invest. 69:1366–1372 (1982).CrossRefPubMedGoogle Scholar
  102. 102.
    G. Ciabattoni, G.A. Cinotti, A. Pierucci et al., Effects of sulindac and ibuprofen in patients with chronic glomerular disease. Evidence for the dependence of renal function on prostacyclin, N. Engl. J. Med. 310:279–283 (1984).CrossRefPubMedGoogle Scholar
  103. 103.
    G.A. FitzGerald, J.A. Oates, J. Hawiger, R.L. Maas, L.J. Roberts, A.R. Brash, Endogenous synthesis of prostacyclin and thromboxane and platelet function during chronic aspirin administration in man, J. Clin. Invest. 71:676–688 (1983).CrossRefPubMedGoogle Scholar
  104. 104.
    A.K. Pedersen and G.A. FitzGerald, Dose-related pharmacokinetics of aspirin: Presystemic acetylation of platelet cyclooxygenase in man, N. Engl. J. Med. 311:1206–1211 (1984).CrossRefPubMedGoogle Scholar
  105. 105.
    A.K. Pedersen, J. Nowak, G.A. FitzGerald, Slow administration of low-dose aspirin: Enhanced inhibition of platelet cyclooxygenase, Circulation 72:7724 (1985).CrossRefGoogle Scholar
  106. 106.
    G. Laffi, G. Daskalopoulos, I. Kronborg, W. Hsueh, P. Gentalini, R.D. Zipser, Effects of sulindac and ibuprofen in patients with cirrhosis and ascites. An explanation for the renal-sparing effect of sulindac, Gastroenterology 90:182–187 (1986).PubMedGoogle Scholar
  107. 107.
    D.C. Brater, S. Anderson, B. Baird, W.B. Campell, Effects of ibuprofen, naproxen, and sulindac on prostaglandins in men, Kidney Int. 27:66–73 (1985).CrossRefPubMedGoogle Scholar
  108. 108.
    L-O. Eriksson, B. Beermann, M. Kallner, Renal function and tubular transport effects of sulindac and naproxen in chronic heart failure, Clin. Pharmacol. Ther. 42:646–654 (1987).CrossRefPubMedGoogle Scholar
  109. 109.
    A.J. Marcus, B.B. Weksler, E.A. Jaffe, M.J. Broekman, Synthesis of prostacyclin from platelet-derived endoperoxides by cultured human endothelial cells, J. Clin. Invest. 66:979–985 (1980).CrossRefPubMedGoogle Scholar
  110. 110.
    A.I. Schäfer, D.D. Crawford, M.A. Gimbrone, Unidirectional transfer of prostaglandin endoperoxides between platelets and endothelial cells, J. Clin. Invest. 73:1105–1111 (1984).CrossRefPubMedGoogle Scholar
  111. 111.
    J. Nowak and G.A. FitzGerald, Prostaglandin endoperoxide reorientation at platelet vascular interface in man, J. Clin. Invest., (in press) (1988).Google Scholar
  112. 112.
    P. Patrignani, P. Filabozzi, F. Catella, F. Pugliese, C. Patrono, Differential effects of dazoxiben, a selective thromboxane synthase inhibitor, on synthase inhibitor, on platelet and renal prostaglandin-endoperoxide metabolism, J. Pharm. Exp. Ther. 228:472–477 (1984).Google Scholar
  113. 113.
    V. Bertele and G. De Gaetano, Potentiation by dazoxiben, a thromboxane synthetase inhibitor, of platelet aggregation inhibitory activity of a thromboxane receptor antagonist and of prostacyclin, Eur. J. Pharmacol. 85:331 (1982).CrossRefPubMedGoogle Scholar
  114. 114.
    G.A. FitzGerald, J. Fragetta, D.J. Fitzgerald, Thromboxane (Tx) synthase inhibition and TxA2/endoperoxide receptor antagonism in a chronic canine model of coronary thrombosis: Effects on TxA2 and prostacyclin (PGI2) biosynthesis, Adv. Prostaglandin. Thromboxane and Leukotriene Res. 17:496–500 (1987).Google Scholar
  115. 115.
    P. Gresele, J. Arnout, H. Deckmyn, J. Vermylen, Endogenous antiaggregatory prostaglandins can contribute to inhibition of hemostasis: A pharmacological study in vivo in humans, in: “Advances in Prostaglandin, Thromboxane, and Leukotriene Research,” Vol. 17, B. Samuelsson, R. Paoletti and P.W. Ramwell, eds., Raven Press, New York, pp. 248–253 (1987).Google Scholar
  116. 116.
    J. Van Reempts, B. Van Deuren, M. Borgers, F. De Clerck, R 68 070, A combined TxA2”Synthetase/TxA2-prostaglandin endoperoxide receptor inhibitor, reduces cerebral infarct size after photochemically initiated thrombosis in spontaneously hypertensive rats, Thromb. Haemost. 58(1):182, 671A (1987).Google Scholar
  117. 117.
    R.A. Armstrong, R.L. Jones, V. Peesapati, S.G. Will, N.H. Wilson, Competitive antagonism at thromboxane receptors in human platelet, Br. J. Pharmac. 84:595–607 (1985).CrossRefGoogle Scholar
  118. 118.
    R.A. Coleman, I. Kennedy, R.L.G. Sheldrick, AH 6809, a prostanoid EP1 receptor-blocking drug, Br. J. Pharmac. Proc. Suppl. 85:273P (1985).Google Scholar
  119. 119.
    D.N. Harris, R. Greenberg, M.B. Phillips, I.M. Michel, H.J. Goldenberg, M.F. Haslanger, T.E. Steinbacher, Effects of SQ 27,427, a thromboxane A2 receptor antagonist in the human platelet and isolated smooth muscle, Eur. J. Pharmacol. 103:9–18 (1984).CrossRefPubMedGoogle Scholar
  120. 120.
    D.N. Harris, M.B. Phillips, I.M. Michel, H.J. Goldenberg, J.E. Heikes, P.W. Sprague, M.J. Antonaccio, 9-Homo-9,11-epoxy, 5,13-prostadienoic acid analogues: Specific stable agonist (SQ 26,538) and antagonist (SQ 26,536) of the human platelet thromboxane receptor, Prostaglandins 22:295–307 (1981).PubMedGoogle Scholar
  121. 121.
    M.L. Ogletree, D.N. Harris, R. Greenberg, M.F. Haslanger, M. Nakane, Pharmacological actions of SQ 29,548, a novel selective thromboxane antagonist, J. Pharmacol. Exp. Ther. 234:435–441 (1985).PubMedGoogle Scholar
  122. 122.
    Huzoor-Akbar, A. Mukhopadhyay, K.S. Anderson, S.S. Navran, K. Romstedt, D.D. Miller, D.R. Feller, Antagonism of prostaglandin-mediated responses in platelets and vascular smooth muscle by 13-azaprostanoic acid analogs, Biomed. Pharmacol. 34:641–647 (1985).Google Scholar
  123. 123.
    G.C. Le Breton, J.P. Lipowski, H. Feinberg, D.L. Venton, T. Ho, K.K. Wu, Antagonism of thromboxane A2/prostaglandin H2 by 13-azaprostanoic acid prevents platelet deposition to the de-endothelialized rabbit aorta in vivo, J. Pharmacol. Exp. Ther. 229:80–84 (1984).PubMedGoogle Scholar
  124. 124.
    M. Fujioka, T. Nagao, H. Kuriyama, Actions of the novel thromboxane A2 antagonists, ONO-1270 and ONO-3708, on smooth muscle cells of the guinea-pig basilar artery, Archives of Pharmacol. 334:468–474 (1986).CrossRefGoogle Scholar
  125. 125.
    M. Katsura, T. Miyamoto, N. Hamanaka, K. Kondo, T. Terada, Y. Ohgaki, A. Kawasaki, M. Tsuboshima, In vitro and in vivo effects of new powerful thromboxane antagonists (3-alkylamino pinane derivatives), in: “Advances in Prostaglandin, Thromboxane and Leukotriene Research,” Vol. 11, B. Samuelsson, R. Paoletti and P. Ramwell, eds., Raven Press, New York, pp. 351–357 (1983).Google Scholar
  126. 126.
    D.J. Fitzgerald, J. Doran, E.K. Jackson, G.A. FitzGerald, Coronary vascular occlusion mediated through thromboxane A2-prostaglandin endo-peroxide receptor activation in vivo, J. Clin. Invest. 77:496 – 502 (1986).CrossRefPubMedGoogle Scholar
  127. 127.
    W.A. Schumacher, H.J. Goldenberg, D.N. Harris, M.L. Ogletree, Effect of thromboxane receptor antagonists on renal artery thrombosis in the cynomolgus monkey, J. Pharmacol. Exp. Ther. 242:460–466 (1987).Google Scholar
  128. 128.
    J.H. Ashton, M.L. Ogletree, I.M. Michel, P. Golino, J.M. McNatt, A.L. Taylor, S. Raheja, J. Schmitz, L.M. Buja, W.B. Campbell, J.T. Willerson, Cooperative mediation by serotonin S2 and thromboxane A2/prostaglandin H2 receptor activation of cyclic flow variations in dogs with severe coronary artery stenoses, Circulation 76: 952–959 (1987).CrossRefPubMedGoogle Scholar
  129. 129.
    P.G. Kuehl, J.M. Bolds, J.E. Lloyd, J. Snapper, G.A. FitzGerald, Thromboxane A2/prostaglandin endoperoxide activation mediates bronchial and hemodynamic responses to endotoxemia in the conscious sheep, Am. J. Physiol. 254 (Regulatory Integrative Comp. Physiol. 23):R310–R319 (1988).Google Scholar
  130. 130.
    J.J. Reeves and R. Stables, Thromboxane receptors can modulate gastric acid secretion in the rat, Prostaglandins 34:829–840 (1987).PubMedGoogle Scholar
  131. 131.
    P. Golino, J.H. Ashton, P. Glas-Greenwalt, J. McNatt, L.M. Buja, J.T. Wilierson, Mediation of reocclusion by thromboxane A2 and serotonin after thrombolysis with tissue-type plasminogen activator in a canine preparation of coronary thrombosis, Circulation 77:676–684 (1988).CrossRefGoogle Scholar
  132. 132.
    D.J. Fitzgerald, J. Fragetta, G.A. FitzGerald, Prostaglandin endoperoxides modulate the response to thromboxane synthase inhibition during coronary thrombosis, J. Clin. Invest.. (submitted) (1988).Google Scholar
  133. 133.
    D.J. Fitzgerald, F. Catella, L. Roy, G.A. FitzGerald, Marked platelet activation in vivo following intravenous streptokinase in acute myocardial infarction, Circulation 77:142–150 (1988).CrossRefPubMedGoogle Scholar
  134. 134.
    Ettie et al, (submitted) (1988).Google Scholar
  135. 135.
    D. Schlondorff, The glomerular mesangial cell: An expanding role for a specialized pericyte, FASEB J. 1:272–281 (1987).PubMedGoogle Scholar
  136. 136.
    J. Sraer, W. Siess, L. Moulonguet-Dolerias, J-P. Oudinet, F. Dray, R. Ardaillou, In vitro prostaglandin synthesis by various rat renal preparations, Biochim. Biophys. Acta. 710:45–52 (1982).CrossRefPubMedGoogle Scholar
  137. 137.
    J.G. Gerber, E. Ellis, J. Hollifield, A.S. Nies, Effect of prostaglandin endoperoxide analogue on canine renal function, hemodynamics and renin release, Eur. J. Pharmacol. 53:239–246 (1979).CrossRefPubMedGoogle Scholar
  138. 138.
    R. Loutzenhiser, M. Epstein, C. Horton, P. Sonke, Reversal of renal and smooth muscle actions of the Am. J. Physiol. 250:F619–F626 (1986).PubMedGoogle Scholar
  139. 139.
    R.M. Burch and P.V. Halushka, Thromboxane and stable prostaglandin endoperoxide analogs stimulate water permeability in the toad urinary bladder, J. Clin. Invest. 66:1251–1257 (1980).CrossRefPubMedGoogle Scholar
  140. 140.
    R.M. Burch and P.V. Halushka, Alterations in extracellular calcium concentration differentially influence prostaglandin and thromboxane synthesis in epithelial cells from the toad urinary bladder, Archives Biochem. Biophys. 229:90–97 (1984).CrossRefGoogle Scholar
  141. 141.
    F. Goto, E.K. Jackson, A. Ohnishi, W. Herzer, R.A. Branch, Effect of cyclooxygenase and thromboxane synthase inhibition on the response to angiotensin II in the hypoperfused canine kidney, J. Pharmacol. Exp. Ther. 242:799–803 (1987).Google Scholar
  142. 142.
    N.M. Thomson, S.R. Holdsworth, E.F. Glasgow, D.K. Peters, R.C. Atkins, Mechanisms of injury in experimental glomerulonephritis, in: “Progress in Glomerulonephritis,” P. Kincaid-Smith, C Aprice and R.C. Atkins, eds., John Wiley and Sons, New York, pp. 51–72 (1979).Google Scholar
  143. 143.
    E.R. Unanue and F.J. Dixon, Experimental glomerulonephritis, VI. The autologous phase of nephrotoxic nephritis, J. Exp. Med. 121:715–725 (1965).CrossRefPubMedGoogle Scholar
  144. 144.
    J.E. Stork and M.J. Dunn, Hemodynamic roles of thromboxane A2 and prostaglandin E2 in glomerulonephritis, J. Pharmacol. Exp. Ther. 233:672–678 (1985).PubMedGoogle Scholar
  145. 145.
    H. Saito, T. Ideura, J. Takeuchi, Effects of a selective thromboxane A2 synthetase inhibitor on immune complex glomerulonephritis, Nephron 36:38–45 (1984).CrossRefPubMedGoogle Scholar
  146. 146.
    G.J. Trachte, Thromboxane agonist (U46619) potentiates norepinephrine efflux from adrenergic nerves, J. Pharmacol. Exp. Ther. 237:473–477 (1986).PubMedGoogle Scholar
  147. 147.
    P. Hedqvist, Control by prostaglandin E2 of sympathetic neurotransmission in the spleen, Life Sci. 9:269–278 (1970).CrossRefPubMedGoogle Scholar
  148. 148.
    P. Hedqvist, Basic mechanisms of prostaglandin action on autonomic neurotransmission, Ann. Rev. Pharmacol. Toxicol. 17:259–279 (1977).CrossRefGoogle Scholar
  149. 149.
    E.K. Jackson, H.D. Uderman, W.A. Herzer, R.A. Branch, Attenuation of noradrenergic neurotransmission by the thromboxane synthetase inhibitor, UK38,485, Life Sci. 35:221–228 (1984).CrossRefPubMedGoogle Scholar
  150. 150.
    E.K. Jackson, F. Goto, H.D. Uderman, R.J. Workman, R.A. Branch, Inhibition of thromboxane A2 (TxA2) synthetase attenuates the renin secretion response to suprarenal aortic clamping, but not to sodium arachidonate, Proceedings of the SCOR-Hypertension Symposium, Sept. 23–24, Cleveland, Ohio (1983).Google Scholar
  151. 151.
    R.A. Branch, F. Goto, W. Ohnishi, W. Herzer, E.K. Jackson, Renal thromboxane A2 release stimulated by angiotensin II in the hypoperfused canine kidney, in: “Advances in Prostaglandin, Thromboxane, and Leukotriene Research,” Vol. 17, B. Samuelsson, R. Paoletti and P.W. Ramwell, eds., Raven Press, New York, pp. 749–756 (1987).Google Scholar
  152. 152.
    S.I. Himmelstein, W.E. Yarger, P.E. Klotman, Altered eicosanoid production by the contralateral kidney in the two-kidney, one clip Goldblatt hypertensive rat, J. Hyperten. 4(suppl.5):S165-S167 (1986).Google Scholar
  153. 153.
    Y. Vanrenterghem, T. Lerut, L. Roels, J. Gruwetz, P. Michielsen, Thromboembolic complications and haemostatic changes in cyclosporin-treated cadaveric kidney allograft recipients, Lancet v:8436–1002 (1985).Google Scholar
  154. 154.
    H. Cohen, G.H. Nield, R. Patel, I.J. Mackie, Machin and S.J. Machin, Evidence for chronic platelet hyperaggregability and in vivo activation in cyclosporin-treated renal allograft recipients, Thromb. Res. 49:91–101 (1988).CrossRefPubMedGoogle Scholar
  155. 155.
    G. Remuzzi, A. Benigni, N. Perico, Renal prostaglandins and hyperfiltration, in: “Advances in Prostaglandin, Thromboxane, and Leukotriene Research,” Vol. 17, B. Samuelsson, R. Paoletti and P.W. Ramwell, eds., Raven Press, New York, pp. 719–724 (1987).Google Scholar
  156. 156.
    J.V. Donadio, C.F. Anderson, J.C. Mitchell et al., Membrano-proliferative glomerulonephritis. A prospective clinical trial of platelet-inhibitor therapy, N. Engl. J. Med. 310:1421–1426 (1984).CrossRefPubMedGoogle Scholar
  157. 157.
    A. Pierucci, B.M. Simonetti, G. Pecci, G. Mavrikakis, S. Feriozzi, G.A. Cinotti, G. Ciabattoni, C. Patrono, Acute effects of a thromboxane receptor antagonist on renal function in patients with lupus nephritis, Kidney Int. 31:283A (1987).Google Scholar
  158. 158.
    J.V. Donadio, Jr., D.M. Ilstrup, K.E. Holley, J.C. Romero, Plateletinhibitor treatment of diabetic nephropathy: a 10-year prospective study, Mavo Clin. Proc. 63:3–15 (1988).CrossRefGoogle Scholar
  159. 159.
    A.H. Barnett, K. Wakelin, B.A. Leatherdale, J.R. Britton, A. Polak, J. Bennett, M. Toop, D. Rowe, K. Dallinger, Specific thromboxane synthetase inhibition and albumin excretion rate in insulin-dependent diabetes, Lancet 1:1322 (1984).CrossRefPubMedGoogle Scholar
  160. 160.
    H. Tyler, Pfizer, Inc., Personal communication (1985).Google Scholar
  161. 161.
    P. Alessandrini, J. McRae, S.S. Feman, G.A. FitzGerald, Thromboxane biosynthesis and platelet function in endogenous biosynthesis of Type I diabetes mellitus, N. Engl. J. Med.. (in press) (1988).Google Scholar
  162. 162.
    R.P. Zipser, S. Hoef, P.F. Speckart, P.K. Zia, R. Horton, Prostaglandins: Modulators of renal function and pressor resistance in chronic liver disease, J. Clin. End. Metab. 48:895–900 (1979).CrossRefGoogle Scholar
  163. 163.
    R.D. Zipser, G.H. Radvan, I.J. Kronberg, R. Duke, T.E. Little, Urinary thromboxane B2 and prostaglandin Eo in the hepatorenal syndrome: Evidence for increased vasoconstrictor and decreased vasodilator factors, Gastroent. 84:697–703 (1983).Google Scholar
  164. 164.
    G.A. FitzGerald, R.L. Maas, R. Stein, J.A. Oates, L.J. Roberts, Intravenous prostacyclin in thrombotic thrombocytopenic purpura, Annals Intern. Med. 95:319–322 (1981).Google Scholar
  165. 165.
    G. Remuzzi and N. Perico, Prostacyclin in thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, in: “Prostaglandins in Clinical Medicine. Cardiovascular and Thrombotic Disorders,” K. Wu and E.C. Rossi, eds., Year Book Medical Publishers, Chicago, pp. 319–324 (1981).Google Scholar
  166. 166.
    G. Remuzzi, M. Livio, A.E. Cavenaghi, D. Marchesi, G. Mecca, M.B.Donati, G. De Gaetano, Unbalanced prostaglandin synthesis and plasma factors in uremic bleeding. A hypothesis, Thromb. Res. 13:531–536 (1978).CrossRefPubMedGoogle Scholar
  167. 167.
    M.C. Smith and M.J. Dunn, Impaired platelet thromboxane production in renal failure, Nephron 29:133–137 (1981).CrossRefPubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Garret A. FitzGerald
    • 1
  • Rosemary Murray
    • 1
  • Patricia Price
    • 1
  • Francesca Catella
    • 1
  1. 1.Division of Clinical PharmacologyVanderbilt UniversityNashvilleUSA

Personalised recommendations