Bidirectional control of CNS capillary diameter by pericytes.
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 techniques. 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 arterioles, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins, 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 approximately 2 microm 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 (gamma-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.
Peppiatt
Claire M
CM
Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.
Howarth
Clare
C
Mobbs
Peter
P
Attwell
David
D
D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001160:Arterioles / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002196:Capillaries / Q000033:anatomy & histology* / Q000187:drug effects / Q000502:physiology*; D002531:Cerebellum / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007511:Ischemia / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000187:drug effects; D012171:Retinal Vessels / Q000187:drug effects / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid; D000255:Adenosine Triphosphate; D002118:Calcium; D009638:Norepinephrine