Noradrenaline released from locus coeruleus axons contracts cerebral capillary pericytes via α₂ adrenergic receptors

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 Ca²⁺ concentration, while the α₁ agonist phenylephrine did not evoke contraction. Blocking α₂ adrenergic receptors (α₂Rs, which induce contraction by inhibiting cAMP production), greatly reduced the NA-evoked pericyte contraction, whereas stimulating α₂Rs using xylazine (a sedative) or clonidine (an anti-hypertensive drug) evoked pericyte contraction. Noradrenaline-evoked pericyte contraction and capillary constriction are thus mediated via α₂Rs. Consequently, α₂Rs may not only modulate CBF in health and pathological conditions, but also contribute to CBF changes evoked by α₂R ligands administered in research, veterinary and clinical settings.