Skip to main content

Thank you for visiting nature.com. 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.

  • Letter
  • Published:

Bidirectional control of CNS capillary diameter by pericytes

Nature volume 443, pages 700–704 (2006)Cite this article

Abstract

Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques1,2,3. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles4, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles5,6, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins7, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at ∼2 µm s-1 to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (γ-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.

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

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1: Pericyte anatomy confers flow-regulating capability downstream of arterioles.
Figure 2: Electrical stimulation evokes Ca 2+ -dependent localized constriction of retinal pericytes.
Figure 3: Propagation and transmitter evocation of retinal pericyte constriction.
Figure 4: Effects of neurotransmitters on cerebellar molecular layer capillary and effects of ischaemia on retinal capillary.

Similar content being viewed by others

References

  1. Roy, C. & Sherrington, C. On the regulation of the blood supply of the brain. J. Physiol. (Lond.) 11, 85–100 (1890)

    Article  CAS  Google Scholar 

  2. Raichle, M. E. Behind the scenes of functional brain imaging: a historical and physiological perspective. Proc. Natl Acad. Sci. USA 95, 765–772 (1998)

    Article  ADS  CAS  Google Scholar 

  3. Attwell, D. & Iadecola, C. The neural basis of functional brain imaging signals. Trends Neurosci. 25, 621–625 (2002)

    Article  CAS  Google Scholar 

  4. Cohen, Z., Molinatti, G. & Hamel, E. Astroglial and vascular interactions of noradrenaline terminals in the rat cerebral cortex. J. Cereb. Blood Flow Metab. 17, 894–904 (1997)

    Article  CAS  Google Scholar 

  5. Berg, B. R., Cohen, K. D. & Sarelius, I. H. Direct coupling between blood flow and metabolism at the capillary level in striated muscle. Am. J. Physiol. 272, H2693–H2700 (1997)

    CAS  PubMed  Google Scholar 

  6. Iadecola, C., Yang, G., Ebner, T. J. & Chen, G. Local and propagated vascular responses evoked by focal synaptic activity in cerebellar cortex. J. Neurophysiol. 78, 651–659 (1997)

    Article  CAS  Google Scholar 

  7. Herman, I. M. & D'Amore, P. A. Microvascular pericytes contain muscle and nonmuscle actins. J. Cell Biol. 101, 43–52 (1985)

    Article  CAS  Google Scholar 

  8. Rucker, H. K., Wynder, H. J. & Thomas, W. E. Cellular mechanisms of CNS pericytes. Brain Res. Bull. 51, 363–369 (2000)

    Article  CAS  Google Scholar 

  9. Kawamura, H. et al. ATP: a vasoactive signal in the pericyte-containing microvasculature of the rat retina. J. Physiol. (Lond.) 551, 787–799 (2003)

    Article  CAS  Google Scholar 

  10. Kawamura, H. et al. Effects of angiotensin II on the pericyte-containing microvasculature of the rat retina. J. Physiol. (Lond.) 561, 671–683 (2004)

    Article  CAS  Google Scholar 

  11. Wu, D. M., Kawamura, H., Sakagami, K., Kobayashi, M. & Puro, D. G. Cholinergic regulation of pericyte-containing retinal microvessels. Am. J. Physiol. Heart Circ. Physiol. 284, H2083–H2090 (2003)

    Article  CAS  Google Scholar 

  12. Hirase, H., Creso, J., Singleton, M., Bartho, P. & Buzsaki, G. Two-photon imaging of brain pericytes in vivo using dextran-conjugated dyes. Glia 46, 95–100 (2004)

    Article  Google Scholar 

  13. Hughes, S. & Chan-Ling, T. Characterization of smooth muscle cell and pericyte differentiation in the rat retina in vivo. Invest. Ophthalmol. Vis. Sci. 45, 2795–2806 (2004)

    Article  Google Scholar 

  14. Zonta, M. et al. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nature Neurosci. 6, 43–50 (2003)

    Article  CAS  Google Scholar 

  15. Mulligan, S. J. & MacVicar, B. A. Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature 431, 195–199 (2004)

    Article  ADS  CAS  Google Scholar 

  16. Takano, T. et al. Astrocyte-mediated control of cerebral blood flow. Nature Neurosci. 9, 260–267 (2006)

    Article  CAS  Google Scholar 

  17. Newman, E. A. Propagation of intercellular calcium waves in retinal astrocytes and Muller cells. J. Neurosci. 21, 2215–2223 (2001)

    Article  CAS  Google Scholar 

  18. Leffler, C. W., Beasley, D. G. & Busija, D. W. Cerebral ischemia alters cerebral microvascular reactivity in newborn pigs. Am. J. Physiol. 257, H266–H271 (1989)

    CAS  PubMed  Google Scholar 

  19. Nelson, C. W., Wei, E. P., Povlishock, J. T., Kontos, H. A. & Moskowitz, M. A. Oxygen radicals in cerebral ischemia. Am. J. Physiol. 263, H1356–H1362 (1992)

    CAS  PubMed  Google Scholar 

  20. Hauck, E. F., Apostel, S., Hoffmann, J. F., Heimann, A. & Kempski, O. Capillary flow and diameter changes during reperfusion after global cerebral ischemia studied by intravital video microscopy. J. Cereb. Blood Flow Metab. 24, 383–391 (2004)

    Article  Google Scholar 

  21. Hansen, A. J. Effect of anoxia on ion distribution in the brain. Physiol. Rev. 65, 101–148 (1985)

    Article  CAS  Google Scholar 

  22. Butryn, R. K., Ruan, H., Hull, C. M. & Frank, R. N. Vasoactive agonists do not change the caliber of retinal capillaries of the rat. Microvasc. Res. 50, 80–93 (1995)

    Article  CAS  Google Scholar 

  23. Schonfelder, U., Hofer, A., Paul, M. & Funk, R. H. In situ observation of living pericytes in rat retinal capillaries. Microvasc. Res. 56, 22–29 (1998)

    Article  CAS  Google Scholar 

  24. Shepro, D. & Morel, N. M. Pericyte physiology. FASEB J. 7, 1031–1038 (1993)

    Article  CAS  Google Scholar 

  25. Sakagami, K., Kawamura, H., Wu, D. M. & Puro, D. G. Nitric oxide/cGMP-induced inhibition of calcium and chloride currents in retinal pericytes. Microvasc. Res. 62, 196–203 (2001)

    Article  CAS  Google Scholar 

  26. Haefliger, I. O., Zschauer, A. & Anderson, D. R. Relaxation of retinal pericyte contractile tone through the nitric oxide–cyclic guanosine monophosphate pathway. Invest. Ophthalmol. 35, 991–997 (1994)

    CAS  Google Scholar 

  27. Simard, M., Arcuino, G., Takano, T., Liu, O. S. & Nedergaard, M. Signaling at the gliovascular interface. J. Neurosci. 23, 9254–9262 (2003)

    Article  CAS  Google Scholar 

  28. Duffy, S. & MacVicar, B. A. Adrenergic calcium signaling in astrocyte networks within the hippocampal slice. J. Neurosci. 15, 5535–5550 (1995)

    Article  CAS  Google Scholar 

  29. Cauli, B. et al. Cortical GABA interneurons in neurovascular coupling: relays for subcortical vasoactive pathways. J. Neurosci. 24, 8940–8949 (2004)

    Article  CAS  Google Scholar 

  30. Metea, M. R. & Newman, E. A. Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. J. Neurosci. 26, 2862–2870 (2006)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank C. Auger for initiating the experiments on cerebellar capillaries. This work was supported by the Wellcome Trust, the EU and a Wolfson-Royal Society Award. C.H. is in the 4-year PhD Programme in Neuroscience at UCL.

Author information

Author notes

  1. Claire M. Peppiatt and Clare Howarth: *These authors contributed equally to this work

Authors and Affiliations

  1. Department of Physiology, University College London, Gower Street, WC1E 6BT, London, UK

    Claire M. Peppiatt, Clare Howarth, Peter Mobbs & David Attwell

Authors
  1. Claire M. Peppiatt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clare Howarth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Mobbs
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David Attwell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Attwell.

Ethics declarations

Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Methods and Supplementary Figure and Movie legends. (PDF 435 kb)

Supplementary Movie 1

Electrically-evoked pericyte constriction and propagation of pericyte constriction along retinal capillaries. (MOV 679 kb)

Supplementary Movie 2

UTP-evoked constriction of retinal capillaries. (MOV 640 kb)

Supplementary Movie 3

Noradrenaline-evoked constriction and glutamate-evoked dilation in a molecular layer capillary in a cerebellar slice. (MOV 1107 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Peppiatt, C., Howarth, C., Mobbs, P. et al. Bidirectional control of CNS capillary diameter by pericytes. Nature 443, 700–704 (2006). https://doi.org/10.1038/nature05193

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05193

This article is cited by

Search

Advanced search

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