Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:


Lymph vessels, Na+ and the teleological science of hypertension

A recent study reports that adenosine A2A receptor-mediated lymphangiogenesis increases lymphatic clearance of excess Na+ from the skin and reduces blood pressure, whereas impairment of this process leads to salt-sensitive hypertension. These findings raise intriguing physiological questions regarding the relationships among sodium, water and blood pressure.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The relationships among body Na+, water and blood pressure.


  1. Krebs, H. A. Excursion into the borderland of biochemistry and philosophy. Bull. Johns Hopkins Hosp. 95, 45–51 (1954).

    CAS  PubMed  Google Scholar 

  2. Guyton, A. C. The surprising kidney-fluid mechanism for pressure control–its infinite gain! Hypertension 16, 725–730 (1990).

    Article  CAS  PubMed  Google Scholar 

  3. Brands, M. W. Unifying approach for interpreting the physiological effect of high salt intake. Hypertension 75, 620–622 (2020).

    Article  CAS  PubMed  Google Scholar 

  4. Zhuang, T. et al. A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension. Eur. Heart J. 44, 2730–2742 (2023).

    Article  PubMed  Google Scholar 

  5. Wiig, H. et al. Immune cells control skin lymphatic electrolyte homeostasis and blood pressure. J. Clin. Invest. 123, 2803–2815 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Machnik, A. et al. Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats. Hypertension 55, 755–761 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. Machnik, A. et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism. Nat. Med. 15, 545–552 (2009).

    Article  CAS  PubMed  Google Scholar 

  8. Nikpey, E. et al. High-salt diet causes osmotic gradients and hyperosmolality in skin without affecting interstitial fluid and lymph. Hypertension 69, 660–668 (2017).

    Article  CAS  PubMed  Google Scholar 

  9. Nosalski, R. & Guzik, T. J. Skin sodium, lymphatics, and blood pressure: a non-canonical mechanism of salt-sensitive hypertension. Eur. Heart J. 44, 2743–2745 (2023).

    Article  PubMed  Google Scholar 

  10. Wiener, N. Cybernetics: Or Control and Communication in the Animal and the Machine, 2nd revised edn (Herman & Cie, The Technology Press, John Wiley & Sons, 1948).

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Jens M. Titze.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Titze, J.M. Lymph vessels, Na+ and the teleological science of hypertension. Nat Rev Nephrol 19, 692–693 (2023).

Download citation

  • Published:

  • Issue Date:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing