Nitric oxide synthase inhibition modulates n-methyl-d-aspartate-
induced changes in cerebral blood flow and eeg activity.
Pelligrino, Dale A., Robert L. Gay Iii, Verna L. Baughman, and Qiong
Wang.
Dept. of Anesthesiology, Univ. of Illinois-Chicago, Chicago, IL
60612, USA
APStracts 3:0221H, 1996.
The effects of nitric oxide synthase (NOS) inhibition on the cerebral
blood flow (CBF) and EEG changes accompanying intravenous
administration of the excitatory amino acid receptor agonist, N
-methyl-D-aspartate (NMDA) were examined in anesthetized rats. Two NOS
inhibition strategies were used--chronic nitro-L-arginine (L-NA)
administration (100 mg x kg-1 x day-1, i.p., over 4 days) and acute
L-NA administration (100 mg x kg-1, infused i.v. over 1 hour). In
both cases, cortical CBF was continuously monitored on study days
using laser-Doppler flowmetry, and EEG was recorded, along with
measurements of total EEG power. In all rats, the NMDA was given as a
1 min i.v. infusion (20 mg x kg-1). During all experiments, arterial
pressure was controlled within the autoregulatory range. Results from
rats treated chronically with L-NA or its enantiomer, D-NA, were
compared. In the acute treatment group, two NMDA infusions were
given, separated by 90 min, with a 1 hour L-NA infusion interposed.
Control rats received saline in place of the L-NA. Both L-NA
treatment protocols significantly increased the duration of NMDA
-induced alterations in EEG activity, relative to controls. NMDA
induced a transient 40-100% increase in cortical CBF that was blocked
by acute but not chronic L-NA administration. These results indicate
that: a) under normal circumstances, NO is the principal mediator of
NMDA-induced cerebrovasodilation; b) with chronic NOS inhibition,
NMDA-induced vasodilation returns to normal, implying replacement of
NO by other factors; and c) NO acts as a negative feedback modulator
of NMDA-induced changes in brain activity.
Received 5 September 1995; accepted in final form 7 February
1996.
APS Manuscript Number H838-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 June 96