Noradrenaline released from locus coeruleus axons contracts cerebral capillary pericytes via α(2) 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 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.