Increased synthesis of nitric oxide in rat brain cortex due to halogenated volatile anesthetics confirmed by EPR spectroscopy.
BACKGROUND
Halogenated volatile anesthetics (HVAs) are considered to be inhibitors of nitric oxide synthase (NOS). On other hand, NO mediates the vasodilation produced by HVAs. Thus, both increase and decrease of NO concentration in brain tissues are possible during anesthesia. Previously, we have observed an increase of NO content in rat brain cortex under halothane anesthesia. The goal of this study was to determine whether the observed phenomenon was general for this anesthetic group, if it was specific for brain cortex, and if the NO increase was due changes in NOS activity.


METHODS
NO scavengers were injected to adult rats 30 min prior to anesthesia. Rats were anesthetized by inhalation of an O2 mixture with volatile anesthetics (1.5% for halothane; 1% for isoflurane, 2% for sevoflurane). After 30 min of anesthesia, rats were decapitated and brain cortex, cerebellum, liver, heart, kidneys and testes were dissected, frozen in liquid nitrogen and subjected to EPR spectroscopy. Nitric oxide content was determined quantitatively based on the intensity of the NO-Fe-DETC complex spectrum and its comparison with the calibration curve.


RESULTS
In rats anesthetized with HVAs, we observed a greater than twofold increase of NO content in brain cortex as compared to the nonanesthetized animals. No significant changes were detected in other organs. The NOS inhibitor N(omega)-nitro-L-arginine abolished the increase of NO content in brain produced by volatile anesthetics.


CONCLUSIONS
The action of volatile anesthetics is coupled with an increase of NO content in the cortex dependent on NOS activity.
Baumane
L
L
Latvian Institute of Organic Synthesis, Riga, Latvia.
Dzintare
M
M
Zvejniece
L
L
Meirena
D
D
Lauberte
L
L
Sile
V
V
Kalvinsh
I
I
Sjakste
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002138:Calibration; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006221:Halothane / Q000494:pharmacology; D007530:Isoflurane / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D019097:Spin Trapping; D013268:Stimulation, Chemical
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D008738:Methyl Ethers; D019335:Nitroarginine; D009569:Nitric Oxide; D019344:Lactic Acid; D000077149:Sevoflurane; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D007530:Isoflurane; D019001:Nitric Oxide Synthase; D006221:Halothane