Stroke, Vol 25, 692-703, Copyright © 1994 by American Heart Association
FM Faraci and JE Brian Jr
BACKGROUND: Nitric oxide (NO) is a potent vasodilator that was initially
described as the mediator of endothelium-dependent relaxation
(endothelium-derived relaxing factor, EDRF). It is now known that NO is
produced by a variety of other cell types. SUMMARY OF REVIEW: Endothelium
produces NO (EDRF) under basal conditions and in response to a variety of
vasoactive stimuli in large cerebral arteries and the cerebral
microcirculation. Endothelium-dependent relaxation is impaired in the
presence of several pathophysiological conditions. This impairment may
contribute to cerebral ischemia or stroke. Activation of glutamate
receptors appears to be a major stimulus for production of NO by neurons.
Neuronally derived NO may mediate local increases in cerebral blood flow
during increases in cerebral metabolism. NO synthase-containing neurons
also innervate large cerebral arteries and cerebral arterioles on the brain
surface. Activation of parasympathetic fibers that innervate cerebral
vessels produces NO-dependent increases in cerebral blood flow. Increases
in cerebral blood flow during hypercapnia also appear to be dependent on
production of NO. Astrocytes may release some NO constitutively, but
astrocytes and microglia can release relatively large quantities of NO
after induction of NO synthase in response to endotoxin or some cytokines.
Expression of inducible NO synthase, perhaps in response to local
production of cytokines, may exert cytotoxic effects in brain during or
after ischemia. CONCLUSIONS: Because endothelium, neurons, and glia can all
produce NO in response to some stimuli, the influence of NO on the cerebral
circulation appears to be very important. Under normal conditions,
constitutively produced NO influences basal cerebral vascular tone and
mediates vascular responses to a diverse group of stimuli. The inducible
form of NO synthase produces much greater amounts of NO that may be an
important mediator of cytotoxicity in brain.
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Nitric oxide and the cerebral circulation
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
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