Skip to main content
SpringerLink
Log in

Blood Pressure and the Renal Actions of AT2 Receptors

  • Hot Topic
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Angiotensin type-2 receptors (AT2Rs) in the renal proximal tubule inhibit sodium (Na+) reabsorption by inducing renal cyclic GMP formation and internalizing and inhibiting major Na+ transporters Na+-H+ exchanger-3 (NHE-3) and Na+/K+ATPase (NKA). Instead of angiotensin II (Ang II), angiotensin III (Ang III) is the predominant endogenous agonist for this response. Exogenous non-peptide AT2R agonist Compound-21 induces natriuresis and lowers blood pressure (BP) in normal and Ang II-infused hypertensive rodents. Spontaneously hypertensive rats (SHR; both pre-hypertensive and hypertensive) have defective natriuretic responses to Ang III, suggesting a defect in AT2R-mediated natriuresis in SHR that leads to hypertension. The mechanisms of deficient AT2R-mediated natriuresis in SHR are unknown but could involve either pre-receptor or receptor/post-receptor defects.

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

Fig. 1

Similar content being viewed by others

References

  1. Carey RM, Siragy HM. Newly recognized components of the renin-angiotensin system: potential roles in cardiovascular and renal regulation. Endocr Rev. 2003;24:261–71.

    Article  CAS  PubMed  Google Scholar 

  2. Carey RM. Newly discovered components and actions of the renin-angiotensin system. Hypertension. 2013;62:818–22.

    Article  CAS  PubMed  Google Scholar 

  3. Carey RM, Padia SH. AT2 receptors: beneficial counter-regulatory role in cardiovascular and renal function. Pflugers Arch. 2013;465:99–110.

    Article  PubMed  Google Scholar 

  4. 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;96:6506–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Crowley SD, Gurley SB, Hererra MJ, Ruiz P, Griffiths R, Kumar AP, Kim HS, Smithies O, Le TH, Coffman TM. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci U S A. 2006;103:17985–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gurley SB, Riquier-Brison AD, Schnermann J, Sparks MA, Allen AM, Hasse VH, Snouwart JN, Le TH, McDonough AA, Koller BH, Coffman TM. AT1A angiotensin receptors in the renal proximal tubule regulate blood pressure. Cell Metab. 2011;13:469–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ozono R, Wang Z-Q, Moore AF, Inagami T, Siragy HM, Carey RM. Expression of the subtype-2 angiotensin (AT2) receptor protein in rat kidney. Hypertension. 1997;30:1238–46.

    Article  CAS  PubMed  Google Scholar 

  8. Padia SH, Howell NL, Siragy HM, Carey RM. Renal angiotensin type 2 receptors mediate natriuresis via angiotensin III in the angiotensin II type 1 receptor-blocked rat. Hypertension. 2006;47:537–44.

    Article  CAS  PubMed  Google Scholar 

  9. Padia SH, Kemp BA, Howell NL, Siragy HM, Fournie-Zaluski M-C, Roques BP, Carey RM. Intrarenal aminopeptidase N inhibition augments natriuretic responses to angiotensin III in angiotensin type 1 receptor-blocked rats. Hypertension. 2007;49:625–30.

    Article  CAS  PubMed  Google Scholar 

  10. Padia SH, Kemp BA, Howell NL, Fournie-Zaluski M-C, Roques BP, Carey RM. Conversion of renal angiotensin II to angiotensin III is critical for AT2 receptor-induced natriuresis in rats. Hypertension. 2008;51:460–5.

    Article  CAS  PubMed  Google Scholar 

  11. Kemp BA, Bell JF, Rottkamp DM, Howell NL, Shao W, Navar LG, Padia SH, Carey RM. Intrarenal angiotensin III is the predominant agonist for proximal tubule angiotensin type 2 receptors. Hypertension. 2012;60:387–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kemp BA, Howell NL, Gildea JJ, Keller SR, Padia SH, Carey RM. AT2 receptor activation induces natriuresis and lowers blood pressure. Circ Res. 2014;115:388–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kemp BA, Howell NL, Keller SR, Gildea JJ, Padia SH, Carey RM. AT2 receptor activation prevents sodium retention and reduces blood pressure in angiotensin II-dependent hypertension. Circ Res. 2016;119:532–43.

    Article  CAS  PubMed  Google Scholar 

  14. Padia SH, Kemp BA, Howell NL, Gildea JJ, Keller SR, Carey RM. Intrarenal angiotensin III infusion induces natriuresis and AT2 receptor translocation in WKY but not in SHR. Hypertension. 2009;53:338–43.

    Article  CAS  PubMed  Google Scholar 

  15. Padia SH, Howell NL, Kemp BA, Fournie-Zaluski M-C, Roques BP, Carey RM. Intrarenal aminopeptidase N inhibition restores defective angiotensin AT2 receptor-mediated natriuresis in SHR. Hypertension. 2010;55:474–80.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, VA, 22908, USA

    Robert M. Carey

Authors
  1. Robert M. Carey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert M. Carey.

Ethics declarations

Conflict of Interest

Dr. Carey declares no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carey, R.M. Blood Pressure and the Renal Actions of AT2 Receptors. Curr Hypertens Rep 19, 21 (2017). https://doi.org/10.1007/s11906-017-0720-7

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11906-017-0720-7

Keywords

Search

Navigation