The Role Of Nitric Oxide In The Convulsion Induced By Lidocaine In Rats

Objective: To investigate the potential mechanism of the convulsion induced by lidocaine by using the selective antagonist of nNOS-7-nitroindazole (7-NI) and determining the activity of nNOS and NO concentration of extracellular fluid in the rats'hippocampal CA1 region.Method: Twenty-four male Wistar rats were randomly divided into three grougs (n=8): sham group (group S), lidocaine group (group L) and group 7-NI. The model of seizure was induced by lidocaine which was infused continuously via an infusion pump and confirmed by EEG on which high spike waves (wave amplitude>100mv, sustained 5-10s) were seen.group S: EEG electrodes were implanted and the right femoral veins were invasived with 24G trochar. The rate of lactated Ringer's solution infused was 1 ml/hr.group L: EEG electrodes were implanted and the right femoral veins were invasived with 24G trochar. After 110min's( 80+30min )infusion of lactated Ringer's solution, lidocaine was given at a bolus dose of 2mg following by continuous infusion at a rate of 4 mg·kg-1·min-1 until the high spike waves were seen on a relatively calm backgroud in EEG. Lidocaine was immediately stopped when the spike waves were confirmed by two respective persons and the lactated Ringer's solution was then infused at the formal rate.group 7-NI: the other steps were same to group L except for 7-NI intraperitoneal injection 30min at a dose of 30mg/ml before lidocaine infusion.After the above, all rats were deeply anesthsized and fixed with 4% PFA which was perfused via ascending aorta.Then, the rats'brain were carefully sampled and stored under 4℃at a thickness of 0.7-1.0cm. In all 3 groups, microdialysis commenced immediately after the implant of microdialysis probe and microdialyates were collected after a calming-down period of 60 minutes. The lactated Ringer's solution exchanged was drived at rate of 2μl/min. The collected microdialyates were used to determine the concentration of NO by using an assay kit. The specimans of brain were used in immunohistochemistry test for the investigation of nNOS activity. nNOS positive neurons were counted in five high power field of optical microscope.Result :( 1 ) The concentration of NO in the microdialyate:Compared with group S, the NO concentration significantly increased in group L (p<0.05).Compared with group L, the NO concentration significantly decreased in group 7-NI (p<0.05).There were significant differences among them.(2) The activited cells(nNOS positive cell)in CA1 region of the rats'brain:Compared with S group, the activated cells increased significantly in L group(p<0.05).Compared with group L, the activated cells decreased significantly in group 7-NI (p<0.05).There were significant differeances among them(p<0.05).(3) The time when the first high spike waves were seen in the EEG group:There was no rat that high spike waves were seen on the EEG in S group.Compared with group L,the time increased significantly in group 7-NI (p<0.05).Conclusion:The NO in the CA1 region of the rats'brain play a positive role in the convulsion induced by lidocaine.The increase of NO may be attribute to activation of nNOS.