Functional hyperemia in the brain: hypothesis for astrocyte-derived vasodilator metabolites. Stroke 1998 Jan;29(1):229-34
Date
01/28/1998Pubmed ID
9445355DOI
10.1161/01.str.29.1.229Scopus ID
2-s2.0-0031963859 (requires institutional sign-in at Scopus site) 198 CitationsAbstract
BACKGROUND: Cerebral blood flow is tightly coupled to neuronal metabolic activity, a phenomenon referred to as functional hyperemia. The mechanisms underlying functional hyperemia in the brain have been extensively studied, but the link between neuronal activation and nutritive blood flow has yet to be defined. Recent investigations by our laboratory and others have identified a potential role for astrocytes as an intermediary cell type in this process.
SUMMARY OF REVIEW: This short review will develop the hypothesis that cytochrome P450 epoxygenase activity in astrocytes catalyzes formation of epoxyeicosatrienoic acids (EETs), which act as potent dilators of cerebral vessels and are released in response to glutamate receptor activation within astrocytes. Neuronal activity stimulates release of arachidonic acid from the phospholipid pool of astrocytic membranes. We provide evidence that the arachidonic acid released on stimulation of glutamate receptors within astrocytes is metabolized by cytochrome P450 2C11 cDNA enzymes into EETs.
CONCLUSIONS: The EETs thus formed will be released and activate K+ channels, increase outward K+ current, and hyperpolarize the plasma membrane. The resulting membrane hyperpolarization inhibits voltage-gated Ca2+ channels and leads to arteriolar dilation, thereby increasing regional nutritive blood flow in response to neuronal activity.
Author List
Harder DR, Alkayed NJ, Lange AR, Gebremedhin D, Roman RJMESH terms used to index this publication - Major topics in bold
8,11,14-Eicosatrienoic AcidAnimals
Arachidonic Acids
Arterioles
Aryl Hydrocarbon Hydroxylases
Astrocytes
Brain
Calcium Channels
Cell Membrane
Cerebrovascular Circulation
Cytochrome P-450 Enzyme System
Humans
Hyperemia
Membrane Lipids
Membrane Potentials
Neurons
Oxygenases
Phospholipids
Receptors, Glutamate
Steroid 16-alpha-Hydroxylase
Steroid Hydroxylases
Vasodilation
Vasodilator Agents
