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(Stroke. 1996;27:747-752.)
© 1996 American Heart Association, Inc.

Articles

Ketamine Antagonizes Nitric Oxide Release From Cerebral Cortex After Middle Cerebral Artery Ligation in Rats

Shinn-Zong Lin, MD, PhD; Ai-Lin Chiou, BS Yun Wang, MD, PhD

From the Departments of Neurosurgery (S.-Z.L.) and Pharmacology (A.-L.C., Y.W.), National Defense Medical Center, Taipei, Taiwan, Republic of China.

Correspondence to Yun Wang, MD, PhD, Department of Pharmacology, National Defense Medical Center, 18 Se-Yuan Rd, PO Box 90048-504, Taipei, Taiwan, 100 ROC. E-mail yun@ndmc1.ndmctsgh.edu.tw.

Background and Purpose 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, an 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.

Key Words: cerebral ischemia • ketamine • nitric oxide • N-methyl-D-aspartate • rats

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