BQ-123, A PEPTIDIC ENDOTHELIN ETA RECEPTOR ANTAGONIST, PREVENTS THE EARLY CEREBRAL VASOSPASM FOLLOWING SUBARACHNOID HEMORRHAGE AFTER INTRACISTERNAL BUT NOT INTRAVENOUS-INJECTION

The aim of this study was to evaluate the role of endothelin and endothelin ETA receptor in the early cerebral vasoconstriction following subarachnoid hemorrhage (SAH) in the rat SAH induced by injection of autologous blood in the cisterna magna reduced by 22 to 38% cerebral blood flow (CBF) measured with radioactive microspheres at 30, 60 and 120 min after SAH. The cyclic pentapeptide BQ-123, a selective antagonist of the ETA receptor, injected intravenously (3 mg/kg) had no effect on this decrease in CBF. However, intracisternal BQ-123 (10 nmol) completely prevented the decrease in CBF at 60 and 120 min after SAH. These results suggest that BQ-123 does not cross the blood-brain barrier, but demonstrate that endothelin acting on ETA receptor plays a role in the pathogenesis of cerebral vasoconstriction in this rat model of SAH.