Different effects of eNOS and nNOS inhibition on transient forebrain ischemia.
To clarify the functions of nitric oxide (NO) induced by either neuronal NO synthase (nNOS) or endothelial NO synthase (eNOS) after transient cerebral ischemia, we investigated the effects of L-N(5)-(1-iminoethyl)ornithine (L-NIO), a relatively selective eNOS inhibitor, and 7-nitroindazole (7-NI), a relatively selective nNOS inhibitor, on hippocampal dysfunction caused by cerebral ischemia. We measured mean arterial blood pressure (MABP), hippocampal blood flow, direct current (DC) potential, CA1 population spike (PS) and extracellular concentrations of glutamate from rat hippocampus after transient forebrain ischemia, which was induced by four-vessel occlusion for 10 min. L-NIO (20 mg/kg) and 7-NI (25 mg/kg) were administered intraperitoneally 20 min before ischemia. L-NIO, but not 7-NI, increased MABP before, during and after ischemia, compared with the vehicle group. 7-NI, but not L-NIO, reduced the amplitude of anoxic depolarization induced by ischemia. 7-NI recovered the PS amplitude in part 60 min after ischemia. 7-NI, but not L-NIO, reduced the ischemia-induced levels of glutamate. These results indicate that nNOS inhibition with 7-NI improves, at least in part, hippocampal dysfunction after ischemia, while eNOS inhibition with L-NIO worsens it.
Department of Physiology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Min Hai
MH
Jiang
Tomohiro
T
Kaku
Junichi
J
Hada
Yasumasa
Y
Hayashi
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology; D007191:Indazoles / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016548:Prosencephalon / Q000098:blood supply*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
D004791:Enzyme Inhibitors; D007191:Indazoles; C065027:N(G)-iminoethylornithine; D018698:Glutamic Acid; D009952:Ornithine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; C080122:7-nitroindazole