The arginine - nitric oxide pathway and cerebrovascular regulation
in cortical spreading depression.
Fabricius, Martin, M. D., Nuran Akgoren, M. D. and Martin Lauritzen,
M. D.
Department of Clinical Neurophysiology, Rigshospitalet, Department
of Medical Physiology, University of Copenhagen, & Department of
Clinical Neurophysiology, Glostrup Hospital, Copenhagen, Denmark.
APStracts 2:0054H, 1995.
Nerve cells release nitric oxide (NO) in response to activation of
glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype. We
explored the hypothesis that NO influences the changes of cerebral
blood flow (CBF) during cortical spreading depression (CSD), which is
known to be associated with NMDA receptor activation. CBF was
monitored in parietal cortex by laser-Doppler flowmetry in halothane
-anesthetized rats. Under control conditions, CSD induced regular
changes of CBF which consisted of four phases: a brief hypoperfusion
before the DC-shift, a marked CBF rise during the DC-shift, followed
by a smaller, but protracted increase of CBF, and a prolonged CBF
reduction - the oligemia. NOS inhibition by i.v. and/or topical
application of NG-nitro-L-arginine enhanced the brief initial
hypoperfusion, but the CBF increases and the oligemia were unchanged.
L-arginine prevented the development of the prolonged oligemia after
CSD, but had no influence on the marked rise of CBF during CSD.
Animals treated with L-arginine recovered the reduced vascular
reactivity to hypercapnia after CSD much faster than control rats.
Functional denervation of cortical and pial arterioles by TTX
accentuated the pre-CSD hypoperfusion and the oligemia, but did not
affect the CBF increases. The results suggest that NO is important
for the changes of cerebrovascular regulation following CSD. The
observations may have clinical importance, as CBF changes during
migraine may be triggered by CSD.
Received 28 October 1994; accepted in final form 14 February
1995.
APS Manuscript Number H958-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 1 March 1995.