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Endothelin, the kidney, and hypertension

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Abstract

The kidneys play a central role in the long-term regulation of blood pressure and in the pathogenesis of hypertension. A common defect that has been found in all forms of hypertension examined to date is a hypertensive shift in the pressure-natriuresis relationship. A major objective of this brief review is to highlight some of the recent advances in our understanding of the mechanisms whereby the renal endothelin system, via endothelin type A- and endothelin type B-receptor activation, modulates renal pressure-natriuresis and blood pressure regulation under normal physiologic conditions and in certain forms of hypertension.

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References and Recommended Reading

  1. Guyton AC, Coleman TG, Cowley AW Jr, et al.: Arterial pressure regulation: overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med 1972, 52:584–594.

    Article  PubMed  CAS  Google Scholar 

  2. Hall JE, Granger JP: Regulation of fluid and electrolyte balance in hypertension-role of hormones and peptides. In Hypertension: Principles and Practice. Edited by Battegay E, Lip GYH, Bakris GL. Boca Raton: Taylor and Francis; 2005:121–142. This chapter discusses the importance of the kidneys in long-term control of blood pressure and in the pathogenesis of hypertension.

    Google Scholar 

  3. Hall JE, Granger JP: Role of sodium and fluid excretion in hypertension. In Textbook of Hypertension. Edited by Swales JD. Blackwell Scientific Pubs, Oxford; 1994:360–387.

    Google Scholar 

  4. Cowley AW Jr, Roman RJ: The role of the kidney in hypertension. JAMA 1996, 275:1581–1589.

    Article  PubMed  Google Scholar 

  5. Curtis JJ, Luke RG, Dustan HP, et al.: Remission of hypertension after renal transplantation. N Engl J Med 1983, 309:1009–1015.

    Article  PubMed  CAS  Google Scholar 

  6. Karet FE, Lifton RP: Mutations contributing to human blood pressure variation. Recent Prog Horm Res 1997, 52:263–276.

    PubMed  CAS  Google Scholar 

  7. Yanagisawa M, Kurihara H, Kimura S, et al.: A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988, 332:411–415.

    Article  PubMed  CAS  Google Scholar 

  8. Kohan D: Endothelins in the normal and diseased kidney. Am J Kidney Dis 1997, 29:2–26.

    PubMed  CAS  Google Scholar 

  9. Schiffrin EL: Endothelin: potential role in hypertension and vascular hypertrophy. Hypertension 1995, 25:1135–1143.

    PubMed  CAS  Google Scholar 

  10. Simonson MS, Dunn MJ: Endothelin peptides and the kidney. Annu Rev Physiol 1993, 55:249–265.

    Article  PubMed  CAS  Google Scholar 

  11. Schiffrin EL: Vascular endothelin in hypertension. Vascul Pharmacol 2005, 43:19–29. This brief review highlights the importance of endothelin-1 in mediating vascular hypertrophy in certain forms of hypertension.

    Article  PubMed  CAS  Google Scholar 

  12. Granger JP: Endothelin. Am J Physiol Regul Integr Comp Physiol 2003, 285:R298-R301.

    PubMed  CAS  Google Scholar 

  13. Kohan DE: The renal medullary endothelin system in control of sodium and water excretion and systemic blood pressure. Curr Opin Nephrol Hypertens 2006, 15:34–40. This brief review highlights the importance of the renal medullary endothelin system in control of sodium and water excretion and blood pressure.

    Article  PubMed  CAS  Google Scholar 

  14. Kassab S, Novak J, Miller T, et al.: Role of endothelin in mediating the attenuated renal hemodynamics in Dahl saltsensitive hypertension. Hypertension 1997, 30:682–686.

    PubMed  CAS  Google Scholar 

  15. Kassab S, Miller M, Novak J, et al.: Endothelin-A receptor antagonism attenuates the hypertension and renal injury in Dahl salt-sensitive rats. Hypertension 1998, 31:397–402.

    PubMed  CAS  Google Scholar 

  16. Alexander BT, Cockrell KL, Rinewalt AN, et al.: Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II hypertension. Am J Physiol Regul Integr Comp Physiol 2001, 280:R1388-R1392.

    PubMed  CAS  Google Scholar 

  17. Ballew JR, Fink GD: Role of ET-1A receptors in experimental Ang II-induced hypertension in rats. Am J Physiol Regul Integr Comp Physiol 2001, 281:R150-R154.

    PubMed  CAS  Google Scholar 

  18. d’Uscio LV, Moreau P, Shaw S, et al.: Effects of chronic ET-1A-receptor blockade in angiotensin II-induced hypertension. Hypertension 1997, 29:435–441.

    PubMed  CAS  Google Scholar 

  19. Perez del Villar C, Garcia Alonso CJ, Feldstein CA, et al.: Role of endothelin in the pathogenesis of hypertension. May Clin Proc 2005, 80:84–96.

    Article  Google Scholar 

  20. Sasser JM, Pollock JS, Pollock DM: Renal endothelin in chronic angiotensin II hypertension. Am J Physiol Regul Integr Comp Physiol 2002, 283:R243-R248.

    PubMed  CAS  Google Scholar 

  21. Granger JP, Alexander BT, Llinas MT, et al.: Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Hypertension 2001, 38:718–722.

    PubMed  CAS  Google Scholar 

  22. Khalil RA, Granger JP: Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models. Am J Physiol Regul Integr Comp Physiol 2002, 283:R29-R45.

    PubMed  CAS  Google Scholar 

  23. Wilkins FC Jr, Alberola A, Mizelle HL, et al.: Systemic hemodynamics and renal function during long-term pathophysiological increases in circulating endothelin. Am J Physiol Regul Integr Comp Physiol 1995, 268:R375-R381.

    CAS  Google Scholar 

  24. Alexander BT, Rinewalt AN, Cockrell KL, et al.: Endothelin-A receptor blockade attenuates the hypertension in response to chronic reductions in uterine perfusion pressure. Hypertension 2001, 37:485–489. This manuscript provides evidence for a role of ET-1, via ETA receptor activation, in mediating the hypertension in a rat placental ischemia model of preeclampsia.

    PubMed  CAS  Google Scholar 

  25. Granger JP, LaMarca BB, Cockrell K, et al.: Reduced uterine perfusion pressure (RUPP) model for studying cardiovascular-renal dysfunction in response to placental ischemia. Methods Mol Med 2006, 122:383–392.

    PubMed  Google Scholar 

  26. Roberts L, LaMarca B, Fournier L, et al.: Enhanced endothelin synthesis by endothelial cells exposed to sera from pregnant rats with decreased uterine perfusion. Hypertension 2006, 47:615–618.

    Article  PubMed  CAS  Google Scholar 

  27. LaMarca BB, Bennett WA, Alexander BT, et al.: Hypertension produced by reductions in uterine perfusion in the pregnant rat. Role of tumor necrosis factor-alpha. Hypertension 2005, 46:1022–1025.

    Article  PubMed  CAS  Google Scholar 

  28. LaMarca BB, Cockrell K, Sullivan E, et al.: Role of endothelin in mediating tumor necrosis factor-induced hypertension in pregnant rats. Hypertension 2005, 46:82–86.

    Article  PubMed  CAS  Google Scholar 

  29. Dean R, Zhuo J, Alcorn D, et al.: Cellular localization of endothelin receptor subtypes in the rat kidney following in vitro labeling. Clin Exp Pharmacol Physiol 1996, 23:524–531.

    PubMed  CAS  Google Scholar 

  30. Jones CR, Hiley CR, Pelton JT, Miller RC: Autoradiographic localization of endothelin binding sites in kidney. Eur J Pharmacol 1989, 163:379–382.

    Article  PubMed  CAS  Google Scholar 

  31. Karet FE, Kuc RE, Davenport AP: Novel ligands BQ123 and BQ3020 characterize endothelin receptor subtypes ET-1A and ET-1B in human kidney. Kidney Int 1993, 44:36–42.

    PubMed  CAS  Google Scholar 

  32. Nambi P, Pullen M, Wu HL, et al.: Identification of endothelin receptor subtypes in human renal cortex and medulla using subtype-selective ligands. Endocrinology 1992, 131:1081–1086.

    Article  PubMed  CAS  Google Scholar 

  33. Gariepy CE, Cass DT, Yanagisawa M: Null mutation of endothelin receptor type B gene in spotting lethal rats causes aganglionic megacolon and white coat color. Proc Natl Acad Sci U S A 1996, 93:867–872.

    Article  PubMed  CAS  Google Scholar 

  34. Strachan FE, Spratt JC, Wilkinson IB, et al.: Systemic blockade of the endothelin-B receptor increases peripheral vascular resistance in healthy men. Hypertension 1999, 33:581–585.

    PubMed  CAS  Google Scholar 

  35. Gariepy CE, Ohuchi T, Williams SC, et al.: Salt-sensitive hypertension in endothelin-B receptor-deficient rats. J Clin Invest 2000, 105:925–933. This manuscript provides strong evidence for a role of ETB receptors in the regulation of sodium balance and arterial pressure.

    Article  PubMed  CAS  Google Scholar 

  36. Pollock DM, Pollock JS: Evidence for endothelin involvement in the response to high salt. Am J Physiol Renal Physiol 2001, 281:F144-F150.

    PubMed  CAS  Google Scholar 

  37. Bagnall AJ, Kelland NF, Gulliver-Sloan F, et al.: Deletion of endothelial cell endothelin B receptors does not affect blood pressure or sensitivity to salt. Hypertension 2006, In press.

  38. Dowhan A, Yuqiang G, Stricklett PK, et al.: Collecting duct-specific knockout of endothelin-1 causes hypertension and sodium retention. J Clin Invest 2004, 114:504–511. This manuscript provides strong evidence for collecting duct-derived ET-1 in the regulation of sodium balance and arterial pressure in animals manintained on high-sodium intake.

    Article  CAS  Google Scholar 

  39. Ohuchi T, Kuwaki T, Ling G, et al.: Elevation of blood pressure by genetic and pharmacological disruption of the ETB receptor in mice. Am J Physiol Regul Integr Comp Physiol 1999, 276:R1071-R1077.

    CAS  Google Scholar 

  40. Kohzuki M, Johnston CI, Chai SY, et al.: Localization and endothelin receptors in the rat kidney. Eur J Pharmacol 1989, 160:193–194.

    Article  PubMed  CAS  Google Scholar 

  41. Michel H, Backer A, Meyer-Lehnert H, et al.: Rat renal, aortic and pulmonary endothelin-I receptors: effects of changes in sodium and water intake. Clin Sci (Lond) 1993, 85:593–597.

    CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, 39216-4505, Jackson, MS, USA

    Joey P. Granger PhD

Authors
  1. Joey P. Granger PhD
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  2. Sean Abram PhD
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  3. David Stec PhD
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  4. Derrick Chandler PhD
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  5. Joshua Speed BS
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  6. Babbette LaMarca PhD
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Correspondence to Joey P. Granger PhD.

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Granger, J.P., Abram, S., Stec, D. et al. Endothelin, the kidney, and hypertension. Current Science Inc 8, 298–303 (2006). https://doi.org/10.1007/s11906-006-0068-x

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  • DOI: https://doi.org/10.1007/s11906-006-0068-x

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