The effects of
R-type calcium channels on cerebral blood flow (CBF) and vasospasm pathways following
subarachnoid hemorrhage (SAH) have not been well studied. The aim of this study was to investigate the role of
R-type calcium channels in vasospasm development and treatment. Sixty-five rats were randomly divided into four groups:
sham (n = 14), SAH (n = 17), SAH +
nimodipine (n = 17), and SAH +
SNX-482 (n = 17). A prechiasmatic SAH model was constructed on day 0. Then 5 μg of
nimodipine (an
L-type calcium channel antagonist) or 0.1 μg of
SNX-482 (an
R-type calcium channel antagonist) was infused intracisternally on days 1 and 2. On day 3, neurological status was evaluated and CBF was determined using fluorescent
microspheres. The extent of
myosin light chain-2 (MLC2) phosphorylation was determined by
urea-
glycerol polyacrylamide gel electrophoresis, followed by immunoblotting. The relative presence of
R-type calcium channels and
calponin was determined by SDS
polyacrylamide gel electrophoresis, followed by immunoblotting. Numbers of
R-type calcium channels increased following SAH, and neurological deficit, CBF reduction, and enhancement of MLC2 phosphorylation as well as
calponin degradation were all found to be present. There were no statistically significant differences in neurological scores among the SAH, SAH +
nimodipine, and SAH +
SNX-482 groups.
Nimodipine had no significant effect on CBF reduction compared to the SAH group (p > 0.008), whereas
SNX-482 significantly inhibited CBF reduction (p < 0.008). Both MLC2 phosphorylation and
calponin degradation appeared to be inhibited by
SNX-482, whereas the effects of
nimodipine were relatively blunted. We concluded that an
R-type calcium channel antagonist may improve CBF following SAH by partially inhibiting MLC2 phosphorylation and
calponin degradation, and may exceed the potential of an
L-type calcium channel antagonist, which suggests a more crucial role for
R-type calcium channels in the development of SAH vasospasm and its treatment.