Modulation of ischemic excitatory neurotransmitter and gamma-aminobutyric acid release during global temporary cerebral ischemia by selective neuronal nitric oxide synthase inhibition.
Nitric oxide release during cerebral ischemia is the result of both neuronal and endothelial subclasses of nitric oxide synthase (NOS). In this study, we examined the role of specific neuronal NOS inhibition (nNOSI) on excitatory neurotransmitter and gamma-aminobutyric acid (GABA) release during global cerebral ischemia. Microdialysis probes were placed into the striatum of 24 rats. After probe stabilization, rats were randomized to receive 7-nitroindazole (7-NI), a selective nNOSI, in doses of 0, 5, 10, or 20 mg/kg. Temporary global forebrain ischemia was induced for 15 min, followed by 60 min of reperfusion. nNOSI administration did not produce detectable changes in neurotransmitter recovery prior to ischemia. There were significant increases in aspartate (ASP), glutamate (GLU), glycine (GLY), and GABA recovery during ischemia in the absence of nNOSI. 7-NI resulted in an attenuation in GLU, GLY, and GABA recovery during ischemia and reperfusion. No differences in ASP recovery were detected with nNOSI. Differences between the present study and other studies that examine the role of nonspecific constitutive NOSI during cerebral ischemia demonstrate the contribution of neuronal NOS on the modulation of ischemic excitatory neurotransmitter and GABA release.
Kahn
R A
RA
Department of Anesthesiology, Mount Sinai Medical Center, New York, New York 10029, USA. ronvkahn@smtplink.mssm.edu
Panah
M
M
Weinberger
J
J
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D018846:Excitatory Amino Acids / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000201:enzymology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018846:Excitatory Amino Acids; D007191:Indazoles; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D019001:Nitric Oxide Synthase; D005998:Glycine; C080122:7-nitroindazole