Neurovascular signaling in the brain and the pathological consequences of hypertension

Abstract

The execution and maintenance of all brain functions are dependent on a continuous flow of blood to meet the metabolic needs of the tissue. To ensure the delivery of resources required for neural processing and the maintenance of neural homeostasis, the cerebral vasculature is elaborately and extensively regulated by signaling from neurons, glia, interneurons, and perivascular nerves. Hypertension is associated with impaired neurovascular regulation of the cerebral circulation and culminates in neurodegeneration and cognitive dysfunction. Here, we review the physiological processes of neurovascular signaling in the brain and discuss mechanisms of hypertensive neurovascular dysfunction.

Keywords: astrocyte; cerebral blood flow; hypertension; neurovascular coupling; parenchymal arteriole.

Fig. 1.

Neuronal network-specific mechanisms of neurovascular coupling. Signaling mechanisms engaged in the cortex to promote vasodilation and increase cerebral blood flow in response to activation of cholinergic basalocortical afferents via basal forebrain stimulation (A) or activation of glutamatergic thalamocortical afferents via somatosensory stimulation (B). Parenchymal arterioles are depicted at the right of each image. Blue, endothelial cell (EC); pink, smooth muscle cell (SMC); green, astrocyte (A); purple, pyramidal neuron; red, GABA inhibitory interneuron; yellow, vasoactive intestinal peptide (VIP)/choline acyltransferase interneuron; orange, nitric oxide (NO) synthase/neuropeptide Y (NPY) interneuron; turquoise, somatostatin (SOM) interneuron. Neurotransmitters released from ascending afferent neurons are shown in blue for A and orange for B. Mediators derived from pyramidal neurons are shown in purple, interneurons in red, astrocytes in green, and vascular ECs in dark blue. R, receptor; mAChR, muscarinic ACh receptor; nAChR, nicotinic ACh receptor; mGluR, metabotropic glutamate (Glu) receptor; NMDA, N-methyl-d-aspartate; AMPA, α-amino-hydroxy-5-methyl-4-isoxazolepropionic acid; BK, large-conductance Ca²⁺-actived K⁺ channel; Kir, inward rectifier K⁺ channel; P₂YR, P₂Y receptor; EET, epoxyeicosatrienoic acid; EP, PGE₂ receptor; COX, cyclooxygenase.