Skip to main content

Advertisement

SpringerLink
Log in

The role of angiotensin II-stimulated renal tubular transport in hypertension

  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

The kidney contains a renin-angiotensin system that appears to regulate systemic blood pressure. Angiotensin II (Ang II) has stimulatory effects on sodium transport in multiple nephron segments via binding to plasma membrane AT1 receptors. In the proximal tubule, Ang II production is substantial. The stimulatory effect of Ang II on proximal sodium transport is enhanced by renal nerves, and is associated with internalization of apical and basolateral receptors. In the cortical collecting duct, AT1 receptors stimulate transport through apical sodium channels, and in the inner medulla, urea transport is enhanced by Ang II, contributing to increased sodium and water reabsorption. AT1 receptors may also be linked to increased expression of certain tubular sodium transporters. In contrast to the stimulatory effects of AT1 receptors on sodium transport, AT2 receptors expressed in the adult kidney are linked to increased urinary sodium excretion and decreased blood pressure. This suggests that renal tubular AT1 receptor activation serves as a protective mechanism to increase sodium reabsorption and blood pressure when extracellular fluid volume is threatened, whereas AT2 receptors dampen this response. The interplay between these two receptor pathways in the kidney could have significant effects on long-term blood pressure control.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Braam B, Mitchell KD, Fox J, et al.: Proximal tubular secretion of angiotensin II in rats. Am J Physiol 1993, 264:F891-F898.

    PubMed  CAS  Google Scholar 

  2. Seikaly MG, Arant BS Jr, Seney FD Jr: Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest 1990, 86:1352–1357.

    PubMed  CAS  Google Scholar 

  3. Nishiyama A, Seth DM, Navar LG: Renal interstitial fluid concentrations of angiotensins I and II in anesthetized rats. Hypertension 2002, 39:129–134.

    Article  PubMed  CAS  Google Scholar 

  4. Felder RA, Seikaly MG, Cody P, et al.: Immunohistochemical localization of Ang II AT1 receptor in adult rat kidney using a monoclonal antibody. Am J Physiol 1997, 273(1 Pt 2): F170-F177.

    Google Scholar 

  5. Ozono R, Wang ZQ, Moore AF, et al.: Expression of the subtype 2 angiotensin (AT2) receptor protein in rat kidney. Hypertension 1997, 30:1238–1246.

    PubMed  CAS  Google Scholar 

  6. Kennedy CR, Burns KD: Angiotensin II as a mediator of renal tubular transport. Contrib Nephrol 2001, 47–62.

  7. Oliverio MI, Best CF, Smithies O, et al.: Regulation of sodium balance and blood pressure by the AT(1A) receptor for angiotensin II. Hypertension 2000, 35:550–554.

    PubMed  CAS  Google Scholar 

  8. Mangrum AJ, Gomez RA, Norwood VF: Effects of AT (1A) receptor deletion on blood pressure and sodium excretion during altered dietary salt intake. Am J Physiol Renal Physiol 2002, 283:F447-F453.

    PubMed  CAS  Google Scholar 

  9. Ding Y, Davisson RL, Hardy DO, et al.: The kidney androgenregulated protein promoter confers renal proximal tubule cell-specific and highly androgen-responsive expression on the human angiotensinogen gene in transgenic mice. J Biol Chem 1997, 272:28142–28148.

    Article  PubMed  CAS  Google Scholar 

  10. Davisson RL, Ding Y, Stec DE, et al.: Novel mechanism of hypertension revealed by cell-specific targeting of human angiotensinogen in transgenic mice. Physiol Genomics 1999, 1:3–9. This study in transgenic mice shows that selective activation of the RAS within the kidney causes hypertension, independent of the systemic RAS, demonstrating the important role of intrarenal Ang II in blood pressure regulation.

    PubMed  CAS  Google Scholar 

  11. Nishiyama A, Seth DM, Navar LG: Renal interstitial fluid angiotensin I and angiotensin II concentrations during local angiotensin-converting enzyme inhibition. J Am Soc Nephrol 2002, 13:2207–2212.

    Article  PubMed  CAS  Google Scholar 

  12. Quan A, Baum M: Endogenous production of angiotensin II modulates rat proximal tubule transport. J Clin Invest 1996, 97:2878–2882.

    PubMed  CAS  Google Scholar 

  13. Quan A, Baum M: Endogenous angiotensin II modulates rat proximal tubule transport with acute changes in extracellular volume. Am J Physiol 1998, 275(1 Pt 2):F74-F78.

    PubMed  CAS  Google Scholar 

  14. Quan A, Baum M: The renal nerve is required for regulation of proximal tubule transport by intraluminally produced Ang II. Am J Physiol Renal Physiol 2001, 280:F524-F529.

    PubMed  CAS  Google Scholar 

  15. Quan A, Baum M: Renal nerve stimulation augments effect of intraluminal angiotensin II on proximal tubule transport. Am J Physiol Renal Physiol 2002, 282:F1043-F1048. Renal sympathetic nerves augment the stimulatory effect of luminal Ang II on proximal tubule transport, suggesting that Ang II production or action may be enhanced with nerve stimulation.

    PubMed  CAS  Google Scholar 

  16. Thekkumkara T, Linas SL: Role of internalization in AT(1A) receptor function in proximal tubule epithelium. Am J Physiol Renal Physiol 2002, 282:F623-F629. Apical AT1 receptors in the proximal tubule internalize before interacting with G proteins, whereas basolateral AT1 receptors can activate G proteins without internalization, which appears to represent a unique pathway for Ang II to stimulate sodium transport in polarized epithelial cells.

    PubMed  CAS  Google Scholar 

  17. Green DM, Ropper AH, Kronmal RA, et al.: Serum potassium level and dietary potassium intake as risk factors for stroke. Neurology 2002, 59:314–320.

    Article  PubMed  CAS  Google Scholar 

  18. Burns KD, Smith IB: Potassium depletion stimulates mRNA expression of proximal tubule AT1 angiotensin II receptors. Nephron 1998, 78:73–81.

    Article  PubMed  CAS  Google Scholar 

  19. Fryer JN, Burns KD, Ghorbani M, Levine DZ: Effect of potassium depletion on proximal tubule AT1 receptor localization in normal and remnant rat kidney. Kidney Int 2001, 60:1792–1799.

    Article  PubMed  CAS  Google Scholar 

  20. Robey RB, Ruiz OS, Espiritu DJ, et al.: Angiotensin II stimulation of renal epithelial cell na/hco3 cotransport activity: a central role for src family kinase/classic mapk pathway coupling. J Membr Biol 2002, 187:135–145.

    Article  PubMed  CAS  Google Scholar 

  21. Espiritu DJ, Bernardo AA, Robey RB, et al.: A central role for Pyk2-Src interaction in coupling diverse stimuli to increased epithelial NBC activity. Am J Physiol Renal Physiol 2002, 283:F663-F670.

    PubMed  Google Scholar 

  22. Kovacs G, Peti-Peterdi J, Rosivall L, et al.: Angiotensin II directly stimulates macula densa Na-2Cl-K cotransport via apical AT (1) receptors. Am J Physiol Renal Physiol 2002, 282:F301-F306.

    PubMed  Google Scholar 

  23. Peti-Peterdi J, Warnock DG, Bell PD: Angiotensin II directly stimulates ENaC activity in the cortical collecting duct via AT(1) receptors. J Am Soc Nephrol 2002, 13:1131–1135. This is the first direct evidence demonstrating that Ang II stimulates sodium transport in the collecting duct via apical membrane sodium channels. This suggests that Ang II plays an important role in the fine-tune regulation of sodium excretion by the kidney, and thereby also adjusts extracellular fluid volume.

    Article  PubMed  CAS  Google Scholar 

  24. Rohrwasser A, Morgan T, Dillon HF, et al.: Elements of a paracrine tubular renin-angiotensin system along the entire nephron. Hypertension 1999, 34:1265–1274.

    PubMed  CAS  Google Scholar 

  25. Oliverio MI, Delnomdedieu M, Best CF: Abnormal water metabolism in mice lacking the type 1A receptor for Ang II. Am J Physiol Renal Physiol 2000, 278:F75-F82.

    PubMed  CAS  Google Scholar 

  26. Kato A, Klein JD, Zhang C, Sands JM: Angiotensin II increases vasopressin-stimulated facilitated urea permeability in rat terminal IMCDs. Am J Physiol Renal Physiol 2000, 279:F835-F840.

    PubMed  CAS  Google Scholar 

  27. Brooks HL, Allred AJ, Beutler KT, et al.: Targeted proteomic profiling of renal Na(+) transporter and channel abundances in angiotensin II type 1a receptor knockout mice. Hypertension 2002, 39:470–473. This study shows for the first time that AT1 receptors stimulate protein expression of certain renal tubular transporters, indicating a novel mechanism by which Ang II might modulate long-term blood pressure.

    Article  PubMed  CAS  Google Scholar 

  28. Carey RM, Jin XH, Siragy HM: Role of the angiotensin AT2 receptor in blood pressure regulation and therapeutic implications. Am J Hypertens 2001, 14:98S-102S.

    Article  PubMed  CAS  Google Scholar 

  29. Oliverio MI, Kim HS, Ito M, et al.: Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptormediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. Proc Natl Acad Sci U S A 1998, 95:15496–15501.

    Article  PubMed  CAS  Google Scholar 

  30. Carey RM, Howell NL, Jin XH, et al.: Angiotensin type 2 receptor-mediated hypotension in angiotensin type-1 receptor-blocked rats. Hypertension 2001, 38:1272–1277.

    PubMed  CAS  Google Scholar 

  31. Siragy HM, Inagami T, Ichiki T, Carey RM: Sustained hypersensitivity to angiotensin II and its mechanism in mice lacking the subtype-2 (AT2) angiotensin receptor. Proc Natl Acad Sci U S A 1999, 96:6506–6510.

    Article  PubMed  CAS  Google Scholar 

  32. Gross V, Schunck WH, Honeck H, et al.: Inhibition of pressure natriuresis in mice lacking the AT2 receptor. Kidney Int 2000, 57:191–202.

    Article  PubMed  CAS  Google Scholar 

  33. Wehbi GJ, Zimpelmann J, Carey RM, et al.: Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptors. Am J Physiol Renal Physiol 2001, 280:F254-F265.

    PubMed  CAS  Google Scholar 

  34. Moore AF, Heiderstadt NT, Huang E, et al.: Selective inhibition of the renal angiotensin type 2 receptor increases blood pressure in conscious rats. Hypertension 2001, 37:1285–1291. Using intrarenal infusion of antisense oligonucleotides to the AT2 receptor in rats, the authors show that blood pressure increases and urine sodium excretion is impaired. This important study therefore indicates that intrarenal AT2 receptors mediate hypotensive effects, perhaps by directly inhibiting tubular sodium transport.

    PubMed  CAS  Google Scholar 

  35. Siragy HM, Carey RM: The subtype 2 (AT2) angiotensin receptor mediates renal production of nitric oxide in conscious rats. J Clin Invest 1997, 100:264–269.

    Article  PubMed  CAS  Google Scholar 

  36. Siragy HM, El-Kersh MA, De Gasparo M, et al.: Differences in AT2 -receptor stimulation between AT1 -receptor blockers valsartan and losartan quantified by renal interstitial fluid cGMP. J Hypertens 2002, 20:1157–1163.

    Article  PubMed  CAS  Google Scholar 

  37. Jin XH, Siragy HM, Carey RM: Renal interstitial cGMP mediates natriuresis by direct tubule mechanism. Hypertension 2001, 38:309–316.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, The Ottawa Hospital and University of Ottawa, 1967 Riverside Drive, Room 535A, K1H 7W9, Ottawa, Ontario, Canada

    Kevin D. Burns MD, FRCPC

Authors
  1. Kevin D. Burns MD, FRCPC
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ningjun Li MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burns, K.D., Li, N. The role of angiotensin II-stimulated renal tubular transport in hypertension. Current Science Inc 5, 165–171 (2003). https://doi.org/10.1007/s11906-003-0074-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11906-003-0074-1

Keywords

Search

Navigation