From the Cardiovascular Research Center and Department of Physiology,
Medical College of Wisconsin and Clement Zablocki VA Medical Center,
Milwaukee, Wis.
Correspondence to David R. Harder, PhD, Cardiovascular Research Center, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail dharder{at}mcw.edu
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.
© 1998 American Heart Association, Inc.
Basic Science Review
Functional Hyperemia in the Brain
Hypothesis for Astrocyte-Derived Vasodilator Metabolites
Key Words: astrocytes • blood flow • vasodilation
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