Ketamine antagonizes nitric oxide release from cerebral cortex after middle cerebral artery ligation in rats.
OBJECTIVE
Ischemia or hypoxia activates N-methyl-D-aspartate (NMDA) receptors and results in nitric oxide (NO) production. The purpose of this study was to investigate whether an NMDA channel blocker can inhibit NO production during ischemia.


METHODS
Temporary cerebral ischemia was induced by middle cerebral artery ligation while common carotid arteries were clamped bilaterally for 40 minutes in urethane-anesthetized rats. Extracellular NO concentration in the cortex was recorded through Nafion- and porphyrine-coated carbon fiber electrodes. Ketamine, and NMDA channel blocker, was administered (50 mg/kg) intraperitoneally 15 minutes before the cerebral artery ligation.


RESULTS
During middle cerebral artery ligation, cortical NO was increased to its peak (18.76+/-3.36 nmol/L) in 7 minutes and then declined. The overflow of NO can be antagonized by pretreatment with ketamine, dizocilpine maleate (MK801), or N(G)-nitro-L-arginine methyl ester (L-NAME). Local application of nitroprusside also induced NO production. However, this effect was not antagonized by ketamine.


CONCLUSIONS
These findings demonstrated that NO release induced by short-term cerebral ischemia can be attenuated by pretreatment with NMDA antagonists.
Lin
S Z
SZ
Department of Neurosurgery, National Defense Medical Center, Taipei, Republic of China.
Chiou
A L
AL
Wang
Y
Y
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002536:Cerebral Arteries / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D007649:Ketamine / Q000494:pharmacology*; D007700:Kinetics; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D009569:Nitric Oxide; D007649:Ketamine; D016291:Dizocilpine Maleate; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester