PREVENTION OF SUBARACHNOID HEMORRHAGE-INDUCED CEREBRAL VASOSPASM BY ORAL-ADMINISTRATION OF ENDOTHELIN RECEPTOR ANTAGONISTS

The purpose of this study was to investigate the effectiveness of oral treatment with the endothelin (ET)(A/B) receptor antagonist y-phenoxy )-2'-bipyrimidin-4-yl]-benzenesulfonamide (bosentan), and the ET(A) re ceptor antagonist yl-3-benzyl-4-(4-methoxy-phenyl)-4-oxo-but-2-enoic a cid monosodium salt (PD155080), in the prevention of subarachnoid hemo rrhage (SAH)-induced delayed cerebral vasospasm. Double hemorrhage in the rabbit constricted the basilar artery to 34% of control as determi ned by angiography. Oral bosentan and PD155080 administration after th e initial SAH decreased the magnitude of constriction to 9% and 16% of control, respectively. Plasma and cerebrospinal fluid bosentan levels and plasma PD155080 levels were consistent with concentrations report ed to inhibit ET-1 constriction of blood vessels in vitro. These resul ts support the use of oral administration of ET(A/B) and ET(A) recepto r antagonists as potential specific treatment for vasospasm resulting from SAH in humans.