The role of endothelin in the pathogenesis of cerebral vasospasm after
subarachinoid hemorrhage was investigated by evaluating the effect of
FR139317, a novel potent ETA receptor antagonist, on the vasospasm in
a canine two-hemorrhage model. Intracisternal administration of FR139
317 ( 0.1mg ) significantly reduced the vasoconstriction of the basila
r artery at day 7 ( control group, n=6, 61.6 +/- 4.0% , FR139317 treat
ed group, n=6, 75.9 +/- 1.5% of basal diameter, p<0.01 ). In normal an
esthetized dogs, the intracisternal administration of FR139317 did not
a affect the basal diameter of the basilar artery, blood pressure or
heart rate. These results suggest that endothelin plays an important r
ole in the pathogenesis of cerebral vasospasm after subarachnoid hemor
rhage, and that FR139317 could be a valuable tool for preventing vasos
pasm after subarachnoid hemorrhage.