Vasospasm was produced in adult mongrel dogs by a two-
hemorrhage method, and the
spastic basilar arteries were exposed via the transclival route on Day 7. Tonic contraction was produced in the normal canine basilar arteries by a local application of KCl or
serotonin after transclival exposure. The exposed
spastic and tonic basilar arteries then received a topical application of the following: 1-(5-isoquinolinesulfonyl)-2-methyl-piperazine (H-7), a potent inhibitor of
protein kinase C acting at the catalytic domain;
calphostin C, a specific inhibitor of
protein kinase C acting at the regulatory domain; or
calpeptin, a selective inhibitor of
calpain. Both
spastic and tonic basilar arteries were effectively dilated by
H-7.
Calphostin C caused only slight dilation of
spastic basilar arteries but moderate dilation of tonic basilar arteries. Dilation in response to
calpeptin was remarkable in the
spastic basilar arteries but slight in the tonic basilar arteries. The doses of
calphostin C and
calpeptin required to obtain maximum effect were markedly lower in the tonic model than in the
spastic model. The
spastic and tonic models had a similar dose-dependent response to
H-7 but quite a different response to
calphostin C or
calpeptin, suggesting a difference in the function of
protein kinase C and
calpain in the two models. Furthermore, the effect of
calphostin C on the reversal of vasospasm was increased significantly after topical treatment with
calpeptin. It is suggested that the majority of the catalytic domain of
protein kinase C is dissociated from the regulatory domain, probably by a limited proteolysis with
calpain, and is markedly activated in vasospasm.