Nephrology pp 908-914 | Cite as

The Renal Biology of Endothelins

  • Barry M. Brenner
  • Andrew J. King


Endothelin (ET) is distinguished from other endogenous vasoactive peptides by its biphasic pressure response and its sustained duration of action. There is marked regional variability in the sensitivity to either the vasodilatory or the vasoconstrictor effects of ET. The renal vascular bed is exquisitely sensitive and may be an important target organ for ET. The extent to which ET functions as an auto-crine, paracrine, or circulating mediator is as yet unclear. Evidence suggests that ET may play a role as a mediator of chronic volume and blood pressure regulation and contribute to sustained renal ischemia in pathophysiological states. Eventual development of effective blockers of ET action will aid in understanding the in vivo effects of ET.


Atrial Natriuretic Peptide Mesangial Cell Renal Plasma Flow Inositol Trisphosphate Renal Vasoconstriction 
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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  1. 1.
    Brenner BM, Troy JL, Ballermann BJ (1989) Endothelium-dependent vascular responses. Mediators and Mechanisms. J Clin Invest 84: 1373–1378Google Scholar
  2. 2.
    Davies PF, Oleson SP, Clapham DE, Morrel EM, Schoen FJ (1988) Endothelial Communication. State of the art lecture. Hypertension 11: 563–572Google Scholar
  3. 3.
    Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526PubMedCrossRefGoogle Scholar
  4. 4.
    Myers PR, Minor RLJ, Guerra RJ, Bates JN, Harrison DG (1990) Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrocysteine than nitric oxide. Nature 345: 161–163PubMedCrossRefGoogle Scholar
  5. 5.
    Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Yazaki Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415PubMedCrossRefGoogle Scholar
  6. 6.
    Inoue A, Yanagisawa M, Kimura S, Kasuya Y, Miyauchi T, Goto K, Masaki T (1989) The human endothelin family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proc Natl Acad Sci USA 86: 2863–2867PubMedCrossRefGoogle Scholar
  7. 7.
    Marsden PA, Danthuluri NR, Brenner BM, Ballermann BJ, Brock TA (1989) Endothelin action on vascular smooth muscle involves inositol trisphosphate and calcium mobilization. Biochem Biophys Res Commun 158: 86–93PubMedCrossRefGoogle Scholar
  8. 8.
    Whittle BJR, Lopez-Belmonte J, Rees DD (1989) 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: 646–652PubMedCrossRefGoogle Scholar
  9. 9.
    Kohzuki MC, Johnston CI, Chai SY, Casley DJ, Mendelsohn FAO (1989) Localization of endothelin receptors in rat kidney. Eur J Pharmacol 160: 193–194PubMedCrossRefGoogle Scholar
  10. 10.
    Koseki C, Imai M, Hirata Y, Yanagisawa M, Masaki T (1989) Autoradiographic distribution in rat tissues of binding sites for endothelin: a neuropeptide? Am J Physiol 256: R858 - R866PubMedGoogle Scholar
  11. 11.
    Badr KF, Munger KA, Sugiura M, Snajdar RM, Schwartzberg M, Inagami T (1989) High and low affinity binding sites for endothelin on cultured rat glomerular mesangial cells. Biochem Biophys Res Commun 161: 776–781PubMedCrossRefGoogle Scholar
  12. 12.
    Martin ER, Brenner BM, Ballermann BJ (to be published) Heterogeneity of cell surface endothelin receptors. J Biol ChemGoogle Scholar
  13. 13.
    Sugiura M, Snajdar RM, Schwartzberg M, Badr KF, Inagami T (1989) Identification of two types of specific endothelin receptors in rat mesangial cells. Biochem Biophys Res Commun 162: 1396–1401PubMedCrossRefGoogle Scholar
  14. 14.
    Badr KF, Murray JJ, Breyer MD, Takahashi K, Inagami T, Harris RC (1989) Mesangial cell, glomerular and renal vascular responses to endothelin in the rat kidney. J Clin Invest 83: 336–342PubMedCrossRefGoogle Scholar
  15. 15.
    Simonson MS, Wann S, Mene P, Dubyak GR, Kester M, Nakazato Y, Sedor JR, Dunn MJ (1989) Endothelin stimulates phospholipase C, Na/H exchange, c-fos expression, and mitogenesis in rat mesangial cells. J Clin Invest 83: 708–712Google Scholar
  16. 16.
    Kurihara H, Yoshizumi M, Takaku M, Yanagisawa M, Masaki T, Hamaoki M, Kato H, Yazaki Y (1989) Transforming growth factor G3 stimulates the expression of endothelin mRNA by vascular endothelial cells. Biochem Biophys Res Commun 159: 1435–1440PubMedCrossRefGoogle Scholar
  17. 17.
    Yoshizumi M, Kurihara H, Sugiyama T, Takaku F, Yanagisawa M, Masaki T, Yazaki Y (1989) Hemodynamic shear stress stimulates endothelin production by cultured endothelial cells. Biochem Biophys Res Commun 161: 859–864PubMedCrossRefGoogle Scholar
  18. 18.
    Marsden PA, Dorfman DM, Brenner BM, Orkin BJ, Ballermann BJ (1989) Endothelin: gene expression, release and action in cultured cells of the renal glomerulus. Am J Hyper-tens 2 (2): 49AGoogle Scholar
  19. 19.
    Kosaka T, Suzuki N, Matsumoto H, Itoh Y, Yasuhara T, Onda H, Fujino M (1989) Synthesis of the vasoconstrictor peptide endothelin in kidney cells. FEBS Lett 249: 4246CrossRefGoogle Scholar
  20. 20.
    Shichiri M, Hirata Y, Emori T, Ohta K, Nakajima T, Sato K, Sato A, Marumo F (1989) Secretion of endothelin and related peptides from renal epithelial cell lines. FEBS Lett 253: 203–206PubMedCrossRefGoogle Scholar
  21. 21.
    Cairns HS, Rogerson ME, Fairbanks LD, Neild GH, Westwick J (1989) 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: 155–160PubMedCrossRefGoogle Scholar
  22. 22.
    King AJ, Brenner BM, Anderson S (1989) Endothelin: a potent renal and systemic vasoconstrictor peptide. Am J Physiol 256: F1051 - F1058PubMedGoogle Scholar
  23. 23.
    Katoh T, Chang H, Uchida S, Okuda T, Kurakawa K (1990) Direct effects of endothelin in the rat kidney. Am J Physiol 258: F397 - F402PubMedGoogle Scholar
  24. 24.
    Hirata Y, Matsuoka H, Kimura K, Fukui K, Hayakawa H, Suzuki E, Sugimoto T, Yanagisawa M, Masaki T (1989) Renal vasoconstriction by the endothelial cell-derived peptide endothelin in spontaneously hypertensive rats. Circ Res 65: 1370–1379PubMedCrossRefGoogle Scholar
  25. 25.
    Mantymaa P, Leppaluoto J, Ruskoaho H (1990) Endothelin stimulates basal stretch-induced atrial natriuretic peptide secretion from the perfused rat heart. Endocrinology 126: 587–595PubMedCrossRefGoogle Scholar
  26. 26.
    Zeidel ML, Brady HR, Kone BC, Gullans SR, Brenner BM (1989) Endothelin, a peptide inhibitor of Na/K ATPase in intact renal tubular epithelial cells. Am J Physiol 257: C1101 - C1107PubMedGoogle Scholar
  27. 27.
    Loutzenhiser R, Epstein M, Hayashi K, Horton C (1990) Direct visualization of effects of endothelin on the renal microvasculature. Am J Physiol 258: F61 - F68PubMedGoogle Scholar
  28. 28.
    Yuan BH, McMurtry IF, Conger JD (1989) Effect of endothelin on isolated perfused rat afferent and efferent arterioles. Clin Res 37: 586AGoogle Scholar
  29. 29.
    Kon V, Yoshioka T, Fogo A, Ichikawa I (1989) Glomerular actions of endothelin in vivo. J Clin Invest 83: 1762–1767PubMedCrossRefGoogle Scholar
  30. 30.
    Culebras M, Montanes I, Lopez-Farre A, Millas I, Lopez-Novoa JM (1989) Effect of endothelin on renal function and on the contraction of cultured rat mesangial cells. Med Sci Res 17: 245–246Google Scholar
  31. 31.
    Sinmonson MS, Dunn MJ (1990) Endothelin-1 stimulates contraction of rat glomerular mesangial cells and potentiates ß-adrenergic-mediated cyclic adenosine monophosphate accumulation. J Clin Invest 85: 790–797CrossRefGoogle Scholar
  32. 32.
    Komuro I, Kurihara H, Sugiyama T, Yoshizumi M, Takaku F, Yazaki Y (1988) Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett. 238: 249–252PubMedCrossRefGoogle Scholar
  33. 33.
    Myers B (1986) Cyclosporine nephrotoxicity. Kidney Int 30: 964–974PubMedCrossRefGoogle Scholar
  34. 34.
    Dedan J, Perico N, Remuzzi G (1990) Role of endothelin in cyclosporine-induced renal vasoconstriction. Kidney Int 37: 479AGoogle Scholar
  35. 35.
    Kon V, Sugiura M, Inagami T, Harvie BR, Ichikawa I, Hoover RL (1990) Role of endothelin in cyclosporin-induced glomerular dysfunction. Kidney Int 37: 1487–1491PubMedCrossRefGoogle Scholar
  36. 36.
    Gerkins JF (1989) Cyclosporine treatment of normal rats produces a rise in blood pressure and decreased renal vascular responses to nerve stimulated, vasoconstrictors and endothelium-dependent dilators. J Pharmacol Exp Ther 250: 1105–1112Google Scholar
  37. 37.
    Liu J, Chen R, Casley DJ, Nayler WG. Ischemia and reperfusion increase 1251-labeled endothelin-1 binding in rat cardiac membranes. Am J Physiol 258: H829 - H835Google Scholar
  38. 38.
    Badr KF, Kelley VE, Rennke HG, Brenner BM (1986) Roles for thromboxane A and leukotrienes in endotoxin-induced acute renal failure. Kidney Int 30: 474–480PubMedCrossRefGoogle Scholar
  39. 39.
    Morel DR, Lacroix JS, Hemsen A, Steinig A, Pittet JF, Lundberg JM (1989) Increased plasma and pulmonary lymph levels of endothelin during endotoxin shock. Eur J Pharmacol 167: 427–428PubMedCrossRefGoogle Scholar
  40. 40.
    Sugiura M, Inagami T, Kon V (1989) Endotoxin stimulates endothelin-release in vivo and in vitro as determined by radioimmunoassay. Biochem Biophys Res Commun 161: 1220–1227PubMedCrossRefGoogle Scholar
  41. 41.
    Beasley D, Brenner BM, Schwartz JH (1990) Interleukin-1 activates guanylate cyclase in rat vascular smooth muscle cells by inducing nitric oxide. FASEB J 4: 685AGoogle Scholar
  42. 42.
    Tomita K, Ujiie K, Nakanishi T, Tomura S, Matsuda O, Ando K, Shichiri M, Hirata Y, Marumo F (1990) Plasma endothelin levels in patients with acute renal failure (letter). N Engl J Med 321: 1127Google Scholar

Copyright information

© Springer Japan 1991

Authors and Affiliations

  • Barry M. Brenner
    • 1
    • 2
  • Andrew J. King
    • 1
    • 2
  1. 1.Renal Division and Department of MedicineBrigham and Women’s HospitalBostonUSA
  2. 2.The Harvard Center for the Study of Kidney DiseasesHarvard Medical SchoolBostonUSA

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