[H-3] L-N-G-NITROARGININE BINDING AFTER TRANSIENT FOCAL ISCHEMIA AND NMDA-INDUCED EXCITOTOXICITY IN TYPE-I AND TYPE-III NITRIC-OXIDE SYNTHASE NULL MICE
H. Hara et al., [H-3] L-N-G-NITROARGININE BINDING AFTER TRANSIENT FOCAL ISCHEMIA AND NMDA-INDUCED EXCITOTOXICITY IN TYPE-I AND TYPE-III NITRIC-OXIDE SYNTHASE NULL MICE, Journal of cerebral blood flow and metabolism, 17(5), 1997, pp. 515-526
We investigated the density and distribution of nitric oxide synthase
(NOS) binding by quantitative autoradiography using [H-3]L-N-G-nitroar
ginine ([H-3]L-NNA) after transient focal ischemia or intrastriatal in
jection of N-methyl-D-aspartate (NMDA) in wild-type (SV-129 and C57bla
ck/6) and type I (neuronal) and type III (endothelial) NOS-deficient m
ice. The middle cerebral artery (MCA) was occluded by an intraluminal
filament for 3 h followed by 10 min to 7 days of reperfusion. Specific
[H-3]L-NNA binding, observed in the wild-type and type III mutant mou
se at baseline, increased by 50-250% in the MCA territory during ische
mia and the first 3 h of reperfusion. The density of binding sites (B-
max), but not the dissociation constant (K-d), increased significantly
during the ischemic period as did type I NOS mRNA as detected by quan
titative reverse transcription polymerase chain reaction. [H-3]L-NNA b
inding after intrastriatal NMDA injection also increased by 20-230%. I
n the type I NOS-deficient mouse, [H-3]L-NNA binding was low and only
a very small increase was observed after ischemia or excitotoxicity. U
nder conditions of this study, [3H]L-NNA did not bind to type II NOS a
s there was no difference in the distribution or density of [H-3]L-NNA
binding in the rat spleen obtained after lipopolysaccharide treatment
despite induction of NOS type II catalytic activity. Our data suggest
that an ischemic/excitotoxic insult up-regulates type I NOS gene expr
ession and [H-3]L-NNA binding and that this up-regulation may play a p
ivotal role in the pathogenesis of ischemic/excitotoxic diseases.