Effects of an endothelin ET(A)-receptor antagonist, S-0139, on cerebral vasospasm and behavioral changes in dogs intracisternally administered endothelin-1.

The effects of an endothelin ET(A)-receptor selective antagonist, S-0139, were examined using dogs given endothelin-1 (ET-1) into the subarachnoid space. ET-1 at 40 pmol apparently constricted the basilar artery in anesthetized dogs and caused various grades of ataxia, facial clonus, nystagmus and other features in conscious dogs, partially mimicking those which have been reported for conscious rats. S-0139 could completely inhibit both the vasoconstriction and behavioral changes. It could also alleviate the behavioral changes caused by ET-1 in conscious dogs when given after the severe ataxia. We concluded that ET-1 in the subarachnoid space produces behavioral changes via endothelin ET(A)-receptor mediation similar to its cerebral vasoconstricting action, at least, in dogs.