We examined the relationship between
nitric oxide (NO) production and delayed neuronal death (DND), in the rat hippocampus induced by 21 minutes of transient global
ischemia produced by the occlusion of both of the common carotid arteries combined with systemic
hypotension. NO production during
ischemia and reperfusion was investigated by quantifying the
nitrite (NO2-) levels of the in vivo microdialysis samples collected ever 3 minutes from the hippocampus. To determine the origin of NO production, we studied the effects of the focal administration of
NG-nitro-L-arginine methyl ester (
L-NAME), an inhibitor of the constitutive
NO synthase (NOS). We also carried out systemic administration of a selective neuronal NOS inhibitor,
7-nitroindazole (7-NI). Rats were grouped as follows: group 1 (n = 22), vehicle; group 2 (n = 19),
L-NAME; group 3 (n = 12), 7-NI; and group 4 (n = 12), a
sham operation. The role of NO in the hippocampal DND was investigated histologically one week after
ischemia. The level of NO production was significantly decreased in groups 2 and 3 as compared to group 1 in which NO production was significantly increased (p < 0.05). The density of remaining neurons in the CA1 area was significantly reduced only in group 1 (p < 0.01). Taken together, it can be concluded that NO production by neuronal NOS during
ischemia and reperfusion resulted in DND in the CA1 region of the rat hippocampus.