Increased production of nitric oxide metabolites in the hippocampus under isoflurane anaesthesia in rats

There is disagreement concerning the role of nitric oxide (NO) in general a naesthesia. The present study was conducted to determine whether the anaest hetic drug isoflurane alters levels of NO metabolites, NOx (NO2 and NO3), i n the hippocampus of rats during and after anaesthesia. Results showed rest ing hippocampal NOx levels of about 20 pmol in freely moving control rats. Five minutes after the induction of isoflurane anaesthesia (4.72%=4 minimum alveolar concentrations, detected by righting reflex), there was loss of t he righting reflex coincident with a significant elevation in hippocampal N Ox levels. During isoflurane anaesthesia, the maximum NOx concentration ros e approximate to 2.4-fold higher than control levels; the NO3 level increas ed about 5-fold higher than resting levels. NOx levels returned to control levels following discontinuation of the anaesthetic. When rats were pre-tre ated with L-NG-nitro arginine methyl ester, an NO synthase-inhibitor, the i soflurane-induced increases in NOx were markedly suppressed. D-NG-nitro arg inine methyl ester was ineffective in preventing these neurochemical change s, thus indicating the stereoselective nature of the inhibition by L-NG-nit ro arginine methyl ester. Furthermore, L-NG-nitro arginine methyl ester pre -treatment likewise prevented increases in both NO2 and NO3 levels. When ra ts were exposed to 80% nitrous oxide in oxygen, there was loss of the right ing reflex but no change in hippocampal NOx levels. These findings indicate that isoflurane increases production of hippocampal NO and that this may b e pertinent to general anaesthetic drug effects.