Effects of nitric oxide synthase inhibition on extracellular glutamate and cerebral blood flow during forebrain ischemia-reperfusion in rat in vivo.
OBJECTIVE
To evaluate factors involved in global forebrain ischemia-reperfusion, the effects of the systemically administered NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), on changes in extracellular glutamate and cerebral blood flow (CBF) were studied during the early period of global forebrain ischemia-reperfusion, simultaneously measuring the glutamate released in the rat forebrain cortex and cortical CBF.


METHODS
After injection of saline or L-NAME, forebrain ischemia-reperfusion was performed by bilateral carotid artery occlusion with controlled hemorrhagic hypotension (30 mmHg) for 10 min and reperfusion for 60 min. The microdialysis electrode and laser Doppler flowmetry were used for real-time monitoring of glutamate and CBF, respectively.


RESULTS
During ischemia, glutamate increased linearly to over 100 muM and remained elevated 30 min after reperfusion in L-NAME-treated rats. In L-NAME-treated rats, CBF also remained significantly lower than baseline for 30-60 min after reperfusion, and glutamate was higher than in saline-treated rats throughout the experiment.


CONCLUSIONS
A remarkable linear increase in glutamate release was observed during ischemia. L-NAME did not prevent this dramatic glutamate accumulation, and moreover, its level increased during reperfusion. The decrease in CBF response after reperfusion might be a factor of the elevated glutamate after reperfusion due to a decrease in reuptake of glutamate.
Yusa
T
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Department of Anesthesiology, University of the Ryukyus, Faculty of Medicine, 207 Uehara, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan.