Skip to main content
SpringerLink
Log in

The Kidneys, Volume and Blood Pressure Regulation, and Hypertension

  • Chapter
  • First Online:
Disorders of Blood Pressure Regulation

Part of the book series: Updates in Hypertension and Cardiovascular Protection ((UHCP))

Abstract

Control of blood pressure is complex and time-dependent and involves the integration of numerous physiological factors that contribute to short- and long-term regulations. Experimental studies support a central role for the kidneys in the long-term regulation of arterial pressure and in the pathogenesis of hypertension. A pivotal part of the renal-body fluid feedback control system for long-term volume and pressure regulation is the renal-pressure natriuresis mechanism. Renal-pressure natriuresis is abnormal in all types of experimental and clinical hypertension. Chronically elevated blood pressure or hypertension is an important compensatory mechanism that allows maintenance of sodium balance when renal-pressure natriuresis is impaired. A shift of pressure natriuresis may occur as a result of intrarenal abnormalities such as enhanced formation of angiotensin II, reactive oxygen species, and endothelin (via ETA receptor activation) or decreased synthesis of nitric oxide or natriuretic prostanoids. In other instances, the altered kidney function is caused by extrarenal disturbances, such as increased renal sympathetic nervous activity or excessive formation of antinatriuretic hormones, such as aldosterone. This brief review focuses on the importance of the kidneys in the long-term regulation of blood pressure and briefly summarizes the various intra- and extrarenal factors that contribute to abnormal pressure natriuresis in hypertension.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

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

    Article  CAS  PubMed  Google Scholar 

  2. Hall JE (2016) Renal dysfunction, rather than nonrenal vascular dysfunction, mediates salt induced hypertension. Circulation 133(9):894–906

    Article  PubMed  PubMed Central  Google Scholar 

  3. Hall JE, Granger JP (2005) Regulation of fluid and electrolyte balance in hypertension: role of hormones and peptides. In: Battegay EJ, Lip GHY, Bakris GL (eds) Hypertension: principles and practice. Taylor & Francis, Boca Raton, pp 121–142

    Chapter  Google Scholar 

  4. Lifton RP (1996) Molecular genetics of human blood pressure variation. Science 272:676–680

    Article  CAS  PubMed  Google Scholar 

  5. Hall JE, Guyton AC, Smith MJ Jr et al (1980) Blood pressure and renal function during chronic changes in sodium intake: role of angiotensin. Am J Physiol 239:F271–F280

    CAS  PubMed  Google Scholar 

  6. Hall JE, Granger JP, Smith MJ et al (1984) Role of renal hemodynamics and arterial pressure in aldosterone “escape”. Hypertension 6(suppl I):I183–I192

    Article  CAS  PubMed  Google Scholar 

  7. Hall JE, Mizelle HL, Hildebrandt DA et al (1990) Abnormal pressure natriuresis: a cause or a consequence of hypertension? Hypertension 15(6 pt 1):547–559

    Article  CAS  PubMed  Google Scholar 

  8. Hall JE, Granger JP, Hester RL et al (1986) Mechanisms of sodium balance in hypertension: role of pressure natriuresis. J Hypertens 4(suppl 4):S57–S65

    CAS  Google Scholar 

  9. Te Riet L, van Esch JH, Roks AJ et al (2015) Hypertension: renin-angiotensin-aldosterone system alterations. Circ Res 116(6):960–975

    Article  Google Scholar 

  10. Navar LG, Harrison-Bernard LM, Nishiyama A et al (2002) Regulation of intrarenal angiotensin II in hypertension. Hypertension 39:316–322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Coffman TM (2011) Renin angiotensin system under pressure: the search for the essential mechanisms of hypertension. Nat Med 17(11):1402–1409

    Article  CAS  PubMed  Google Scholar 

  12. Crowley SD, Zhang J, Herrera M et al (2011) Role of AT1 receptor-mediated salt retention in angiotensin II-dependent hypertension. Am J Physiol Renal Physiol 301(5):F1124–F1130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Gurley SB, Riquier-Brison AD, Schnermann J et al (2011) AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure. Cell Metab 13(4):469–475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Coffman TM, Crowley SD (2008) Kidney in hypertension: Guyton Redux. Hypertension 51(4):811–816

    Article  CAS  PubMed  Google Scholar 

  15. Luther JM (2016) Aldosterone in vascular and metabolic dysfunction. Curr Opin Nephrol Hypertens 25(1):16–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Epstein M, Calhoun DA (2011) Aldosterone blockers (mineralocorticoid receptor antagonism) and potassium-sparing diuretics. J Clin Hypertens (Greenwich) 13(9):644–648

    Article  CAS  Google Scholar 

  17. Shibata S, Fujita T (2011) The kidneys and aldosterone/mineralocorticoid receptor system in salt-sensitive hypertension. Curr Hypertens Rep 13(2):109–115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Arroyo JP, Lagnaz D, Ronzaud C et al (2011) Nedd4-2 modulates renal Na+-Cl- cotransporter via the aldosterone-SGK1-Nedd4-2 pathway. J Am Soc Nephrol 22(9):1707–1719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. de Paula RB, da Silva AA, Hall JE (2004) Aldosterone antagonism attenuates obesity induced hypertension and glomerular hyperfiltration. Hypertension 43:41–47

    Article  PubMed  Google Scholar 

  20. Calhoun DA, Nishizaka MK, Zaman MA et al (2002) Hyperaldosteronism among black and white subjects with resistant hypertension. Hypertension 40:892–896

    Article  CAS  PubMed  Google Scholar 

  21. DiBona GF (2003) Neural control of the kidney: past, present, and future. Hypertension 4:621–624

    Article  Google Scholar 

  22. DiBona GF, Esler M (2010) Translational medicine: the antihypertensive effect of renal denervation. Am J Physiol Regul Integr Comp Physiol 298(2):R245–R253

    Article  CAS  PubMed  Google Scholar 

  23. Kassab S, Kato T, Wilkins FC et al (1995) Renal denervation attenuates the sodium retention and hypertension associated with obesity. Hypertension 25:893–897

    Article  CAS  PubMed  Google Scholar 

  24. Krum H, Whitbourn R, Sobotka P et al (2009) Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof- of-principle cohort study. Lancet 373:1275–1281

    Article  PubMed  Google Scholar 

  25. Esler MD, Krum H, Sobotka PA et al (2010) Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial. Lancet 376(9756):1903–1909

    Article  PubMed  Google Scholar 

  26. Iliescu R, Lohmeier TE, Tudorancea I et al (2015) Renal denervation for the treatment of resistant hypertension: review and clinical perspective. Am J Physiol Renal Physiol 309(7):F583–F594

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. De Miguel C, Speed JS, Kasztan M et al (2016) Endothelin-1 and the kidney: new perspectives and recent findings. Curr Opin Nephrol Hypertens 25(1):35–41

    Article  PubMed  PubMed Central  Google Scholar 

  28. Nasser SA, El-Mas MM (2014) Endothelin ETA receptor antagonism in cardiovascular disease. Eur J Pharmacol 737:210–213

    Article  CAS  PubMed  Google Scholar 

  29. Kohan DE, Rossi NF, Inscho EW et al (2011) Regulation of blood pressure and salt homeostasis by endothelin. Physiol Rev 91:1–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  32. Krum H, Viskoper RJ, Lacourciere Y et al (1998) The effect of an endothelin receptor antagonist, Bosentan, on blood pressure in patients with essential hypertension. N Engl J Med 338:784–790

    Article  CAS  PubMed  Google Scholar 

  33. Prasad VS, Palaniswamy C, Frishman WH (2009) Endothelin as a clinical target in the treatment of systemic hypertension. Cardiol Rev 17:181–191

    Article  PubMed  Google Scholar 

  34. Goddard J, Kohan D, Pollock D et al (2008) Role of endothelin-1 in clinical hypertension: 20 years on. Hypertension 52:452–459

    Article  PubMed  Google Scholar 

  35. Gariepy CE, Ohuchi T, Williams SC et al (2000) Salt-sensitive hypertension in endothelin-B receptor-deficient rats. J Clin Invest 105:925–933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  37. Bagnall AJ, Kelland NF, Gulliver-Sloan F et al (2006) Deletion of endothelial cell endothelin B receptors does not affect blood pressure or sensitivity to salt. Hypertension 48:286–293

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  39. Ge Y, Bagnall A, Stricklett P, Strait K et al (2006) Collecting duct-specific knockout of the endothelin B receptor causes hypertension and sodium retention. Am J Physiol Renal Physiol 291(6):F1274–F1280

    Article  CAS  PubMed  Google Scholar 

  40. Ge Y, Bagnall A, Stricklett PK et al (2008) Combined knockout of collecting duct endothelin A and B receptors causes hypertension and sodium retention. Am J Physiol Renal Physiol 295(6):F1635–F1640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Schnackenberg CG, Kirchner K, Patel A et al (1997) Nitric oxide, the kidney, and hypertension. Clin Exp Pharmacol Physiol 24:600–606

    Article  CAS  PubMed  Google Scholar 

  42. Granger JP, Alexander BT (2000) Abnormal pressure natriuresis in hypertension: role of nitric oxide. Acta Physiol Scand 168:161–168

    Article  CAS  PubMed  Google Scholar 

  43. Schnackenberg C, Wilkins C, Granger JP (1995) Role of nitric oxide in modulating the vasoconstrictor actions of angiotensin II in preglomerular and postglomerular vessels in dogs. Hypertension 26:1024–1029

    Article  CAS  PubMed  Google Scholar 

  44. Granger JP, Alberola A, Salazer F et al (1992) Control of renal hemodynamics during intrarenal systemic EDNO synthesis blockade. J Cardiovasc Pharmacol 20:S160–S162

    Article  CAS  PubMed  Google Scholar 

  45. Granger JP, Novak J, Schnackenberg C et al (1996) Role of renal nerves in mediating the hypertensive effects of nitric oxide synthesis inhibition. Hypertension 27:613–618

    Article  CAS  PubMed  Google Scholar 

  46. Mattson DL, Lu SH, Nakanishi K et al (1994) Effect of chronic renal medullary nitric oxide inhibition on blood pressure. Am J Physiol Heart Circ Physiol 266:H1918–H1926

    Article  CAS  Google Scholar 

  47. Cowley AW Jr, Mori T, Mattson D et al (2003) Role of renal NO production in the regulation of medullary blood flow. Am J Physiol Regul Integr Comp Physiol 284:R1355–R1369

    Article  CAS  PubMed  Google Scholar 

  48. Knox FG, Granger JP (1992) Control of sodium excretion: an integrative approach. In: Windhager E (ed) Handbook of renal physiology. Oxford University Press, New York, pp 927–967

    Google Scholar 

  49. Granger JP, Opgenorth TJ, Salazar J et al (1986) Long-term hypotensive and renal effects of chronic infusions of atrial natriuretic peptide in conscious dogs. Hypertension 8:II112–II116

    Article  CAS  PubMed  Google Scholar 

  50. Melo LG, Steinhelper ME, Pang SC et al (2000) ANP in regulation of arterial pressure and fluid-electrolyte balance: lessons from genetic mouse models. Physiol Genomics 3:45–58

    Article  CAS  PubMed  Google Scholar 

  51. Melo LG, Veress AT, Chong CK et al (1998) Salt-sensitive hypertension in ANP knockout mice: potential role of abnormal plasma renin activity. Am J Physiol 274:R255–R261

    CAS  PubMed  Google Scholar 

  52. Cheng HF, Harris RC (2004) Cyclooxygenases, the kidney, and hypertension. Hypertension 43:525–530

    Article  CAS  PubMed  Google Scholar 

  53. Roman RJ (2002) P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev 82:131–185

    Article  CAS  PubMed  Google Scholar 

  54. Zhang MZ, Yao B, Wang Y et al (2015) Inhibition of cyclooxygenase-2 in hematopoietic cells results in salt-sensitive hypertension. J Clin Invest 125(11):4281–4294

    Article  PubMed  PubMed Central  Google Scholar 

  55. Taniyama Y, Griendling KK (2003) Reactive oxygen species in the vasculature: molecular and cellular mechanisms. Hypertension 42:1075–1081

    Article  CAS  PubMed  Google Scholar 

  56. Wilcox CS (2002) Reactive oxygen species: roles in blood pressure and kidney function. Curr Hypertens Rep 4:160–166

    Article  PubMed  Google Scholar 

  57. Schreck C, O'Connor PM (2011) NAD(P)H oxidase and renal epithelial ion transport. Am J Physiol Regul Integr Comp Physiol 300(5):R1023–R1029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Manning RD Jr, Meng S, Tian N (2003) Renal and vascular oxidative stress and salt-sensitivity of arterial pressure. Acta Physiol Scand 179:243–250

    Article  CAS  PubMed  Google Scholar 

  59. Garvin JL, Ortiz PA (2003) The role of reactive oxygen species in the regulation of tubular function. Acta Physiol Scand 179:225–232

    Article  CAS  PubMed  Google Scholar 

  60. Sanz-Rosa D, Oubina MP, Cediel E et al (2005) Effect of AT1 receptor antagonism on vascular and circulating inflammatory mediators in SHR: role of NF{kappa}B/I{kappa}B system. Am J Physiol Heart Circ Physiol 288:H111–H115

    Article  CAS  PubMed  Google Scholar 

  61. De Miguel C, Guo C, Lund H et al (2011) Infiltrating T lymphocytes in the kidney increase oxidative stress and participate in the development of hypertension and renal disease. Am J Physiol Renal Physiol 300(3):F734–F742

    Article  PubMed  Google Scholar 

  62. Mattson DL (2010) Effector memory T lymphocytes in renal disease. Am J Physiol Renal Physiol 299(6):F1257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. De Miguel C, Das S, Lund H et al (2010) T lymphocytes mediate hypertension and kidney damage in Dahl salt-sensitive rats. Am J Physiol Regul Integr Comp Physiol 2010 298(4):R1136–R1142

    Article  Google Scholar 

  64. Granger JP, Alexander BT, Llinas MT et al (2002) Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction. Microcirculation 9:147–160

    Article  CAS  PubMed  Google Scholar 

  65. Lee DL, Sturgis LC, Labazi H et al (2006) Angiotensin II hypertension is attenuated in interleukin-6 knockout mice. Am J Physiol Heart Circ Physiol 290:H935–H940

    Article  CAS  PubMed  Google Scholar 

  66. Harrison DG, Guzik TJ, Lob HE et al (2011) Inflammation, immunity, and hypertension. Hypertension 57:132–140

    Article  CAS  PubMed  Google Scholar 

  67. Guzik TJ, Hoch NE, Brown KA et al (2007) Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 204:2449–2460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Crowley SD, Song YS, Lin EE et al (2010) Lymphocyte responses exacerbate angiotensin II-dependent hypertension. Am J Physiol Regul Integr Comp Physiol 298:R1089–R1097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Itani HA, McMaster WG Jr, Saleh MA et al (2016) Activation of human T cells in hypertension: studies of humanized mice and hypertensive humans. Hypertension 68(1):123–132

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Wenzel U, Turner JE, Krebs C et al (2016) Immune mechanisms in arterial hypertension. J Am Soc Nephrol 27(3):677–686

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics, School of Graduate Studies in the Health Sciences, Cardiovascular-Renal Research Center, University of Mississippi Medical Center, 2500 N. State St, Jackson, MS, 39216, USA

    Joey P. Granger Ph.D. & Frank T. Spradley

Authors
  1. Joey P. Granger Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Frank T. Spradley
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joey P. Granger Ph.D. .

Editor information

Editors and Affiliations

  1. Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Adel E. Berbari

  2. Emeritus Professor of Medicine, University of Milano-Bicocca, Monza, Italy

    Giuseppe Mancia

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Granger, J.P., Spradley, F.T. (2018). The Kidneys, Volume and Blood Pressure Regulation, and Hypertension. In: Berbari, A., Mancia, G. (eds) Disorders of Blood Pressure Regulation. Updates in Hypertension and Cardiovascular Protection. Springer, Cham. https://doi.org/10.1007/978-3-319-59918-2_5

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-59918-2_5

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-59917-5

  • Online ISBN: 978-3-319-59918-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation