This study was designed to characterize
nitric oxide (NO) production and anoxic depolarization in the rat hippocampus during transient forebrain
ischemia using two
NO synthase (NOS) inhibitors, L-N(5)-(1-iminoethyl)ornithine (
L-NIO), a relatively selective endothelial NOS (eNOS) inhibitor, and
7-nitroindazole, a relatively selective neuronal NOS (nNOS) inhibitor, and an NO scavenger, [2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-
oxide] (
carboxy-PTIO). We measured the mean arterial blood pressure, hippocampal blood flow, NO concentration and direct current potential before, during and after transient forebrain
ischemia, which was induced by 4-vessel occlusion for 10 min. Saline,
L-NIO (20 mg/kg),
7-nitroindazole (25 mg/kg),
L-NIO (20 mg/kg)+7-nitroindazole (25 mg/kg) or
carboxy-PTIO (1 mg/kg) was administered intraperitoneally 20 min before the onset of
ischemia. We observed early and sharp NO production in the hippocampus during
ischemia in the saline group. This NO increase during
ischemia was significantly reduced by
L-NIO (20 mg/kg)+7-nitroindazole (25 mg/kg) or
carboxy-PTIO (1 mg/kg), but not
L-NIO (20 mg/kg) or
7-nitroindazole (25 mg/kg). On the other hand, NO production after
ischemia was significantly reduced by
7-nitroindazole (25 mg/kg),
L-NIO (20 mg/kg)+7-nitroindazole (25 mg/kg) or
carboxy-PTIO (1 mg/kg), but not
L-NIO (20 mg/kg). The peak latency of NO production during
ischemia always preceded the onset latency of anoxic depolarization in both the saline group and the
carboxy-PTIO group. In the
carboxy-PTIO group, the onset latency of anoxic depolarization was significantly longer than that in the saline group. Moreover,
carboxy-PTIO significantly reduced the anoxic depolarization amplitude, compared with that of the saline group. These results suggest that both NOS-dependent and-independent NO formation contributes to early and sharp NO production during
ischemia, and that this NO increase is, at least in part, related to the triggering of anoxic depolarization.