Pericyte-mediated constriction of renal capillaries evokes no-reflow and kidney injury following ischaemia

  1. Felipe Freitas
  2. David Attwell  Is a corresponding author
  1. University College London, United Kingdom

Abstract

Acute kidney injury is common, with ~13 million cases and 1.7 million deaths/year worldwide. A major cause is renal ischaemia, typically following cardiac surgery, renal transplant or severe hemorrhage. We examined the cause of the sustained reduction in renal blood flow ('no-reflow'), which exacerbates kidney injury even after an initial cause of compromised blood supply is removed. Adult male Sprague-Dawley rats, or NG2-dsRed male mice were used in this study. After 60 min kidney ischaemia and 30-60 min reperfusion, renal blood flow remained reduced, especially in the medulla, and kidney tubule damage was detected as Kim-1 expression. Constriction of the medullary descending vasa recta and cortical peritubular capillaries occurred near pericyte somata, and led to capillary blockages, yet glomerular arterioles and perfusion were unaffected, implying that the long-lasting decrease of renal blood flow contributing to kidney damage was generated by pericytes. Blocking Rho kinase to decrease pericyte contractility from the start of reperfusion increased the post-ischaemic diameter of the descending vasa recta capillaries at pericytes, reduced the percentage of capillaries that remained blocked, increased medullary blood flow and reduced kidney injury. Thus, post-ischaemic renal no-reflow, contributing to acute kidney injury, reflects pericytes constricting the descending vasa recta and peritubular capillaries. Pericytes are therefore an important therapeutic target for treating acute kidney injury.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file.

Article and author information

Author details

  1. Felipe Freitas

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4627-3509
  2. David Attwell

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    For correspondence
    d.attwell@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3618-0843

Funding

Rosetrees Trust and Stoneygate Trust

  • Felipe Freitas
  • David Attwell

Wellcome Trust

  • David Attwell

European Research Council

  • David Attwell

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were performed under UK government Home Office licence 70/8976 in accordance with European Commission Directive 2010/63/EU and the UK Animals (Scientific Procedures) Act (1986), with approval from the UCL Animal Welfare and Ethical Review Body.

Copyright

© 2022, Freitas & Attwell

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Felipe Freitas
  2. David Attwell
(2022)
Pericyte-mediated constriction of renal capillaries evokes no-reflow and kidney injury following ischaemia
eLife 11:e74211.
https://doi.org/10.7554/eLife.74211

Share this article

https://doi.org/10.7554/eLife.74211

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