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Endothelin pp 238-257 | Cite as

Endothelin and the Homeostatic Function of the Endothelial Cell

  • Regina M. Botting
  • John R. Vane
Part of the Clinical Physiology Series book series (CLINPHY)

Abstract

Cultured porcine endothelial cells release a peptide into the culture medium that causes slow, long-lasting contractions of isolated vascular strips.17 This peptide was isolated, characterized, and synthesized in 1988 by Yanagisawa et al.,66 who named it “endothelin.” The endothelin from porcine endothelial cells consists of a chain of 21 amino acids held together by two disulfide bridges and is generated from a precursor molecule by a previously unknown protease. It was subsequently discovered that three isomers of endothelin, expressed by three different genes, are probably present in all mammalian species.22 Endothelin-1 is the only one made by endothelial cells and was first called “porcine” or “human” endothelin. Endothelin-2 is more potent than endothelin-1 and has a longer duration of action on blood pressure. It is not known where it is made except perhaps in kidney cells.27 Endothelin-3, first called “rat” endothelin, may be associated with nervous tissue.67 The structure of endothelin-3 differs from that of endothelin-1 by 6 of the 21 amino acid residues and consists of (Thr2, Phe4, Thr5, Tyr6, Lys7, Tyr14)-substituted endothelin-1. Endothelin-2 differs from endothelin-1 by two amino acids and corresponds to (Trp6, Leu7)-substituted endothelin-1.

Keywords

Platelet Aggregation Sodium Nitroprusside Depressor Response Homeostatic Function Perfuse Kidney 
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.

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References

  1. 1.
    Alheid, U., J. C. Frolich, and U. FÖRstermann. Endothelium-derived relaxing factor from cultured human endothelial cells inhibits aggregation of human platelets. Thromb. Res. 47: 561–571, 1987.PubMedCrossRefGoogle Scholar
  2. 2.
    Axuma, H., M. Ishikawa, and S. Sekizaki. Endothelium-dependent inhibition of platelet aggregation. Br. J. Pharmacol. 88: 411–415, 1986.CrossRefGoogle Scholar
  3. 3.
    Baydoun, A. R., S. H. Peers, G. Cirino, and B. Woodward. Vasodilator action of endothelin1 in the perfused rat heart. J. Cardiovasc. Pharmacol. 15: 759–763, 1990.PubMedCrossRefGoogle Scholar
  4. 4.
    Bennett, T., A. M. Compton, and S. M. Gardiner. Regional haemodynamic effects of endothelin-2 and sarafotoxin-S6b in conscious rats. J. Physiol. 423 22P (abstract) 1990.Google Scholar
  5. 5.
    Boulanger, C., and T. F. LüscHer. Release of endothelin from the porcine aorta: inhibition by endothelium-derived nitric oxide. J. Clin. Invest. 85: 587–590, 1990.PubMedCrossRefGoogle Scholar
  6. 6.
    Cairns, H. S., M. E. Rogerson, L. D. Fairbanks, G. H. Neild, and J. Westwick. Endothelin induces an increase in renal vascular resistance and a fall in glomerular filtration rate in the rabbit isolated perfused kidney. Br. J. Pharmacol. 98: 155–160, 1989.PubMedCrossRefGoogle Scholar
  7. 7.
    Clozel, M., and J.-P. Clozel. Effects of endothelin on regional blood flows in squirrel monkeys. J. Pharmacol. Exp. Ther. 250: 1125–1131, 1989.PubMedGoogle Scholar
  8. 8.
    DE Nucci, G., R. Thomas, P. D’OrlÉAnsjuste, E. Antunes, C. Walder, T. D. Warner, and J. R. Vane. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proc. Natl. Acad. Sci. Usa 85: 9797–9800, 1988.PubMedCrossRefGoogle Scholar
  9. 9.
    D’OrlÉAnsjuste, R., P. S. Lidbury, T. D. Warner, and J. R. Vane. Intravascular big endothelin increases circulating levels of endothelin-1 and prostanoids in the rabbit. Biochem. Pharmacol. 39: R21 - R22, 1990.CrossRefGoogle Scholar
  10. 10.
    Eglen, R. M., A. D. Michel, N. A. Sharif, S. R. Swank, and R. L. Whiting. The pharmacological properties of the peptide endothelin. Br. J. Pharmacol. 97: 1297–1307, 1989.PubMedCrossRefGoogle Scholar
  11. 11.
    Fortes, Z. B., G. DE Nucci, and J. Garcia-Leme Effect of endothelin-1 on arterioles and venules in vivo. J. Cardiouasc. Pharmacol. 13 (Suppl. 5): S200 - S201, 1989.CrossRefGoogle Scholar
  12. 12.
    Fukuda, N., Y. IzuMI, M. Soma, Y. Watanabe, M. Watanabe, M. Hatano, I. Sakuma, and H. Yasuda. L-NG-momomethyl arginine inhibits the vasodilating effects of low dose of endothelin-3 on rat mesenteric arteries. Biochem. Biophys. Res. Commun. 167: 739–745, 1990.PubMedCrossRefGoogle Scholar
  13. 13.
    Gardiner, S. M., A. M. Compton, T. Bennett, R. M. J. Palmer, S. Moncada. The effect of NG-monomethyl-L-arginine (L-Nmma) on the haemodynamic actions of endothelin-1 in conscious Long-Evans rats. Br. J. Pharmacol. 98 626P (abstract), 1989.Google Scholar
  14. 14.
    Given, M. B., R. F. Lowe, H. Lippton, A. L. Hyman, G. E. Sander, and T. D. Giles. Hemodynamic actions of endothelin in conscious and anesthetized dogs. Peptides 10: 41–44, 1989.PubMedCrossRefGoogle Scholar
  15. 15.
    Gryglewski, R. J., R. M. J. Palmer, and S. Moncada. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320: 454–456, 1986.PubMedCrossRefGoogle Scholar
  16. 16.
    Herman, F., K. Magyar, P.-E. Chabrier, P. Braquet, and J. Filep. Prostacyclin mediates antiaggregatory and hypotensive actions of endothelin in anaesthetized beagle dogs. Br. J. Pharmacol. 98: 38–40, 1989.PubMedCrossRefGoogle Scholar
  17. 17.
    Hickey, K. A., G. Rubanyi, R. J. Paul, and R. F. Highsmith. Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am. J. Physiol. 248 (Cell Physiol. 17): C550–0556, 1985.PubMedGoogle Scholar
  18. 18.
    Hiley, C. R., S. A. Douglas, and M. D. Randall. Pressor effects of endothelin-1 and some analogs in the perfused superior mesenteric arterial bed of the rat. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S197 - S199, 1989.PubMedCrossRefGoogle Scholar
  19. Hinojosa-Laborde, C., J. W. Osborn, JR., and A. W. Cowley, JR. Hemodynamic effects of endothelin in conscious rats. Am. J. Physiol. 256(Heart Circ. Physiol. 25): H1742–H1746, 1989.Google Scholar
  20. 20.
    Hoffman, A., E. Grossman, K. P. ÖHman, E. Marks, and H. R. Keiser. Endothelin induces an initial increase in cardiac output associated with selective vasodilation in rats. Life Sci. 45: 249–255, 1989.PubMedCrossRefGoogle Scholar
  21. 21.
    Hughes, A. D., S. A. M. Thom, N. Woodall, M. Schachter, W. M. Hair, G. N. Martin, and P. S. Sever. Human vascular responses to endothelin-1: observations in vivo and in vitro. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S225 - S228, 1989.PubMedCrossRefGoogle Scholar
  22. 22.
    Indue, A., M. Yanagisawa, S. Kimura, Y. Kasuya, T. Miyauchi, K. Goto, and T. Masaki. The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc. Natl. Acad. Sci. Usa 86: 2863–2867, 1989.CrossRefGoogle Scholar
  23. 23.
    Karwatowska-Prokopczuk, E., and A Wennmalm. Effects of endothelin on coronary flow, mechanical performance, oxygen uptake, and formation of purines and on outflow of prostacyclin in the isolated rabbit heart. Circ. Res. 66: 46–54, 1990.PubMedCrossRefGoogle Scholar
  24. 24.
    Kauser, K., G. M. Rubanyi, D. R. Harder. Endothelium-dependent modulation of endothelin-induced vasoconstriction and membrane depolarization in cat cerebral arteries. J. Pharmacol. Exp. Ther. 252: 93–97, 1989.Google Scholar
  25. 25.
    Knuepfer, M. M., S. Ping Han, A. J. Trapani, K. F. Fok, and T. C. Westfall. Regional hemodynamic and baroreflex effects of endothelin in rats. Am. J. Physiol. 257 (Heart Circ. Physiol. 26 ): H918 - H926, 1989.Google Scholar
  26. 26.
    Korbut, R., P. Lidbury, G. R. Thomas, and J. R. Vane. Fibrinolytic activity of endothelin3. Thromb. Res. 55: 797–799, 1989.PubMedCrossRefGoogle Scholar
  27. 27.
    Kosaka, T., N. Suzuki, H. Matsumoto, Y. Itoh, T. Yasuhara, H. Onda, and M. Fujino. Synthesis of the vasoconstrictor peptide in kidney cells. Febs Lett. 249: 42–46, 1989.PubMedCrossRefGoogle Scholar
  28. 28.
    LE Monnier DE Gouville, A. C., and I. Cavero. Haemodynamic profile of endothelin in pithed rats. Br. J. Pharmacol. 96: 95P, 1989.Google Scholar
  29. 29.
    LE Monnier DE Gouville, A. C., S. Mondot, H. Lippton, A. Hyman, and I. Cavero. Hemodynamic and pharmacological evaluation of the vasodilator and vasoconstrictor effects of endothelin-1 in rats. J. Pharmacol. Exp. Ther. 252: 300–311, 1990.Google Scholar
  30. 30.
    LI, L., T. Ishikawa, T. Miyauchi, M. Yanagisawa, S. Kimura, K. Goto, and T. Masaki. Pressor response to endothelin in guinea pigs. Jpn. J. Pharmacol. 49: 549–550, 1989.PubMedCrossRefGoogle Scholar
  31. 31.
    Lidbury, P. S., C. Thiemermann, G. R. Thomas, and J. R. Vane. Endothelin-3: selectivity as an antiaggregatory peptide in vivo. Eur. J. Pharmacol. 166: 335–338, 1989.PubMedCrossRefGoogle Scholar
  32. 32.
    Lidbury, P. S., C. Thiemermann, R. Korbut, and J. R. Vane. Endothelins release tissue plasminogen activator and prostanoids. Eur. J. Pharmacol. 186: 205–212, 1990.PubMedCrossRefGoogle Scholar
  33. 33.
    Lippton, H., J. Goff, and A. Hyman. Effect of endothelin in the systemic and renal vascular beds in vivo. Eur. J. Pharmacol. 155: 197–199, 1988.PubMedCrossRefGoogle Scholar
  34. 34.
    Scher, T. F., Z. Yang, D. Diederich, and F. R. BÜHler. Endothelium-derived vasoactive substances: potential role in hypertension, atherosclerosis, and vascular occlusion. J. Cardiovasc. Pharmacol. 14 (Suppl. 6): S63 - S69, 1989.PubMedGoogle Scholar
  35. 35.
    Maclean, M. R., M. D. Randall, and C. R. Hiley. Effects of moderate hypoxia, hypercapnia and acidosis on haemodynamic changes induced by endothelin-1 in the pithed rat. Br. J. Pharmacol. 98: 1055–1065, 1989.PubMedCrossRefGoogle Scholar
  36. 36.
    Maggi, C. A., S. Giuliani, R. Patacchini, P. Santicioli, P. Rovero, A. Giachetti, and A. Meli. The C-terminal hexapeptide, endothelin-(16–21), discriminates between different endothelin receptors. Eur. J. Pharmacol. 166: 121–122, 1989.PubMedCrossRefGoogle Scholar
  37. 37.
    Mcauley, M. A., I. M. Macrae, and J. L. Reid. Haemodynamic responses to endothelin after peripheral and central administration in the conscious rat. Br. J. Pharmacol. 98, 709P (abstract) 1989.Google Scholar
  38. 38.
    Mcgregor, D. D. The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rat. J. Physiol. (Lond). 177: 21–30, 1965.Google Scholar
  39. 39.
    Miller, W. L., P. G. Cavero, L. L. Aarhus, D. M. Heublein, and J. C. Burnett, JR. Endothelin-mediated arterial vasoconstriction is heterogenous and attenuated by nitroglycerin. Clin. Res. 37: 930A, 1989.Google Scholar
  40. 40.
    Minkes, R. K., D. H. Coy, W. A. Murphy, D. B. Mcnamara, and P. J. Kadowitz. Effects of porcine and rat endothelin and an analog on blood pressure in the anaesthetized cat. Eur. J. Pharmacol. 164: 571–575, 1989.PubMedCrossRefGoogle Scholar
  41. 41.
    Minkes, R. K., and P. J. Kadowitz. Influence of endothelin on systemic arterial pressure and regional blood flow in the cat. Eur. J. Pharmacol. 163: 163–166, 1989.PubMedCrossRefGoogle Scholar
  42. 42.
    Minkes, R. K., and P. J. Kadowitz. Differential effects of rat endothelin on regional blood flow in the cat. Eur. J. Pharmacol. 165: 161–164, 1989.PubMedCrossRefGoogle Scholar
  43. 43.
    Miura, K., T. Yukimara, Y. Yamashita, T. Shimmen, M. Okumura, M. Imanishi, and K. Yamamoto. Endothelin stimulates the renal production of prostaglandin EZ and IZ in anaesthetized dogs. Eur. J. Pharmacol. 170: 91–93, 1989.PubMedCrossRefGoogle Scholar
  44. 44.
    Mortensen, L. H., and G. D. Fink. Hemodynamic effect of human and rat endothelin administration into conscious rats. Am. J. Physiol. 258 (Heart Circ. Physiol. 27 ): H362 - H368, 1990.Google Scholar
  45. 45.
    ÖHlen, A., J. Raud, P. Hedqvist, and N. P. Wiklund. Microvascular effects of endothelin in the rabbit tenuissimus muscle and hamster cheek pouch. Microvasc. Res. 37: 115–118, 1989.PubMedCrossRefGoogle Scholar
  46. 46.
    Palmer, R. M. J., A. G. Ferrige, and S. Moncada. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526, 1987.PubMedCrossRefGoogle Scholar
  47. 47.
    Pernow, J., A. Hemsen, and J. M. Lundberg. Tissue specific distribution, clearance and vascular effects of endothelin in the pig. Biochem. Biophys. Res. Commun. 161: 647–653, 1989.Google Scholar
  48. 48.
    Ping Han, S., A. J. Trapani, K. F. Fox, T. C. Westfall, and M. M. Knuepfer. Effects of endothelin on regional hemodynamics in conscious rats. Eur. J. Pharmacol. 159: 303–305, 1989.Google Scholar
  49. 49.
    Rae, G. A., M. Trybulec, G. DE NuccI, and J. R. Vane. Endothelin-1 releases eicosanoids from rabbit isolated perfused kidney and spleen. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S89 - S92, 1989.PubMedCrossRefGoogle Scholar
  50. 50.
    Rakugi, H., M. Nakamaru, Y. Tabuchi, M. Nagano, H. Mikami, and T. Ogihara. Endothelin stimulates the release of prostacyclin from rat mesenteric arteries. Biochem. Biophys. Res. Commun. 160: 924–928, 1989.PubMedCrossRefGoogle Scholar
  51. 51.
    Randall, M. D., S. A. Douglas, and C. R. Hiley. Vascular activities of endothelin-1 and some alanyl substituted analogues in resistance beds of the rat. Br. J. Pharmacol. 98: 685–699, 1989.PubMedCrossRefGoogle Scholar
  52. Rohmeiss, P., J. Photiadis, S. Rohmeiss, and T. Unger. Hemodynamic actions of intravenous endothelin in rats: comparison with sodium nitroprusside and methoxamine Am. J. Physiol. 258(Heart Circ. Physiol. 27): H337–H346, 1990.Google Scholar
  53. 53.
    Spokes, R. A., M. A. Ghatei, and S. R. Bloom. Studies with endothelin-3 and endothelin-1 on rat blood pressure and isolated tissues: evidence for multiple endothelin receptor subtypes. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S191–5192, 1989.PubMedCrossRefGoogle Scholar
  54. 54.
    Thiemermann, C., P. S. Lidbury, G. R. Thomas, and J. R. Vane. Endothelin-1 releases prostacyclin and inhibits ex vivo platelet aggregation in the anesthetized rabbit. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): 5138–5141, 1989.Google Scholar
  55. 55.
    Thiemermann, C., G. R. May, C. P. Page, and J. R. Vane. Endothelin-1 inhibits platelet aggregation in vivo: a study with mindium-labelled platelets. Br. J. Pharmacol. 99: 303–308, 1990.PubMedCrossRefGoogle Scholar
  56. 56.
    Vanhoute, P. M., W. Auch-Schwelk, C. Boulanger, P. A. Janssen, Z. S. Katusic, K. KoMori, V. M. Miller, V. B. Schini, and M. Vidal. Does endothelin-1 mediate endothelium-dependent contractions during anoxia? J. Cardiovasc. Pharmacol. 13 (Suppl. 5): 5124 - S128, 1989.Google Scholar
  57. 57.
    Walder, C. E., G. R. Thomas, C. Thiemermann, and J. R. Vane. The hemodynamic effects of endothelin-1 in the pithed rat. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S93 - S97, 1989.PubMedCrossRefGoogle Scholar
  58. 58.
    Warner, T. D., G. DE Nuccl, and J. R. Vane. Rat endothelin is a vasodilator in the isolated perfused mesentery of the rat. Eur. J. Pharmacol. 159: 325–326, 1989.PubMedCrossRefGoogle Scholar
  59. 59.
    Warner, T. D., J. A. Mitchell, G. DE NucCI, and J. R. Vane. Endothelin-1 and endothelin3 release Edrf from isolated perfused arterial vessels of the rat and rabbit. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S85 - S88, 1989.PubMedCrossRefGoogle Scholar
  60. 60.
    Whittle, B. J. R., J. Lopezbelmonte, and D. D. Rees. Modulation of the vasodepressor actions of acetylcholine, bradykinin, substance P and endothelin in the rat by a specific inhibitor of nitric oxide formation. Br. J. Pharmacol. 98: 646–652, 1989.PubMedCrossRefGoogle Scholar
  61. 61.
    Whittle, B. J. R., A. N. Payne, and J. V. Esplugues. Cardiopulmonary and gastric ulcerogenic actions of endothelin-1 in the guinea pig and rat. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S103 - S107, 1989.PubMedCrossRefGoogle Scholar
  62. 62.
    Winquist, R. J., P. B. Bunting, V. M. Garsky, P. K. Lumma, and T. L. Schofield. Prominent depressor response to endothelin in spontaneously hypertensive rats. Eur. J. Pharmacol. 163: 199–203, 1989.PubMedCrossRefGoogle Scholar
  63. 63.
    Withrington, P. G., G. DE Nucct, and J. R. Vane. The actions of endothelin on the hepatic arterial and portal vascular beds of the anaesthetised dog. Br. J. Pharmacol. 96, 165P (abstract) 1989.Google Scholar
  64. 64.
    Withrington, P. G., G. DE Nuccl, and J. R. Vane. Endothelin-1 causes vasoconstriction and vasodilation in the blood perfused liver of the dog. J. Cardiovasc. Pharmacol. 13 (Suppl. 5): S209–210, 1989.PubMedCrossRefGoogle Scholar
  65. 65.
    Wright, C. E., and J. R. Fozard. Regional vasodilation is a prominent feature of the haemodynamic response to endothelin in anaesthetized, spontaneously hypertensive rats. Eur. J. Pharmacol. 155: 201–203, 1988.PubMedCrossRefGoogle Scholar
  66. 66.
    Yanagisawa, M., H. Kurihara, S. Kimura, Y. Tomobe, M. Kobayashi, Y. Mitsui, Y. Yazaki, K. GoTO, and T. Masaki. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415, 1988.PubMedCrossRefGoogle Scholar
  67. 67.
    Yanagisawa, M., and T. Masaki. Endothelin, a novel endothelium-derived peptide. Biochem. Pharmacol. 38: 1877–1883, 1989.PubMedCrossRefGoogle Scholar

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© American Physiological Society 1992

Authors and Affiliations

  • Regina M. Botting
  • John R. Vane

There are no affiliations available

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