Noradrenaline released from locus coeruleus axons contracts cerebral capillary pericytes via α 2 adrenergic receptors
Year: 2023
Type: article
Abstract: Noradrenaline (NA) release from locus coeruleus axons generates vascular contractile tone in arteriolar smooth muscle and contractile capillary pericytes. This tone allows neuronal activity to evoke vasodilation that increases local cerebral blood flow (CBF). Much of the vascular resistance within the brain is located in capillaries and locus coeruleus axons have NA release sites closer to pericytes than to arterioles. In acute brain slices, NA contracted pericytes but did not raise the pericyte cytoplasmic Ca 2+ concentration, while the α 1 agonist phenylephrine did not evoke contraction. Blocking α 2 adrenergic receptors (α 2 Rs, which induce contraction by inhibiting cAMP production), greatly reduced the NA-evoked pericyte contraction, whereas stimulating α 2 Rs using xylazine (a sedative) or clonidine (an anti-hypertensive drug) evoked pericyte contraction. Noradrenaline-evoked pericyte contraction and capillary constriction are thus mediated via α 2 Rs. Consequently, α 2 Rs may not only modulate CBF in health and pathological conditions, but also contribute to CBF changes evoked by α 2 R ligands administered in research, veterinary and clinical settings.
Authors: Nils Korte, Greg James, Haoming You, Chanawee Hirunpattarasilp, Isabel Christie, Huma Sethi, David Attwell
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,000
Awards: Control of cerebral blood flow by capillary pericytes in health and disease, The development, plasticity and pathology of myelinated CNS axons., The development, plasticity and pathology of myelinated CNS axons., Understanding the cellular neurobiology of paediatric stroke and moyamoya disease
OpenAlex ID: W4317780814