The permanent occlusion of bilateral common carotid arteries (2VO) in rats has been shown to cause progressive and long-lasting cognitive deficits which may be due to impairment of memory retention and/or memory recall process. To clarify the function of
voltage dependent calcium channels and the receptor binding of
nimodipine by chronic
cerebral ischemia, we examined specific (+)-[3H]
PN 200-110 binding and the effect of
oral administration of
nimodipine in brain regions and hearts of rats, at 2 weeks to 4 months after permanent 2VO. There was no significant difference in either dissociation constant (Kd) or maximal number of binding sites (Bmax) for (+)-[3H]
PN 200-110 in the cerebral cortex, hippocampus, corpus striatum and thalamus between 2VO and
sham rats. In addition, in vitro inhibitory effect of
nimodipine on cerebral cortical (+)-[3H]
PN 200-110 binding in 2VO rats was similar to that in
sham rats. Compared to control rats,
oral administration of
nimodipine to both 2VO and
sham rats at 2 months after permanent 2VO brought about a significant increase in Kd values of specific (+)-[3H]
PN 200-110 binding in the cerebral cortex, hippocampus, thalamus and myocardium, and the increase in Kd values was much larger in brain regions of 2VO rats than
sham rats. However, the increase in Kd values in the myocardium did not differ between 2VO and
sham rats. This observation suggests an increased in vivo binding affinity for
nimodipine in chronic ischemic brain. In conclusion, the present study has shown that
oral administration of
nimodipine may cause a greater occupation in vivo of
1,4-dihydropyridine (DHP)
calcium channel antagonist receptors in brains of permanent 2VO rats than in
sham rats. Thus,
nimodipine may be pharmacologically effective in preventing brain dysfunction due to
cerebral ischemia in vivo.