title: NO synthase inhibition modulates NMDA-induced changes in cerebral blood flow and EEG activity.
abstract: The effects of nitric oxide synthase (NOS) inhibition on the cerebral blood flow (CBF) and electroencephalographic (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 N omega-nitro-L-arginine (L-NNA) administration (100 mg.kg-1.day-1 ip, over 4 days) and acute L-NNA administration (100 mg/kg iv infused over 1 h). 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 intravenous infusion (20 mg/kg). During all experiments, arterial pressure was controlled within the autoregulatory range. We compared the results from rats treated chronically with L-NNA or its enantiomer. N omega-nitro-D-arginine. In the acute treatment group, two NMDA infusions were given, separated by 90 min, interposed by a 1-h L-NNA infusion. Control rats received saline in place of the L-NNA. Both L-NNA 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-NNA administration. These results indicate that 1) under normal circumstances nitric oxide is the principal mediator of NMDA-induced cerebrovasodilation; 2) with chronic NOS inhibition, NMDA-induced vasodilation returns to normal, implying replacement of nitric oxide by other factors; and 3) nitric oxide acts as a negative feedback modulator of NMDA-induced changes in brain activity.
authors.affiliation: Department of Anesthesiology, College of Medicine, University of Illinois, Chicago 60612, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Pelligrino
authors.forename: R L
authors.initials: RL
authors.lastname: Gay
authors.forename: V L
authors.initials: VL
authors.lastname: Baughman
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004569:Electroencephalography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D019335:Nitroarginine; D016202:N-Methylaspartate; D019001:Nitric Oxide Synthase