AN ENDOTHELIN ET(A) RECEPTOR ANTAGONIST, FR139317, AMELIORATES CEREBRAL VASOSPASM IN DOGS

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.