Cocaine-induced Endothelin-1-dependent Spasm in Rabbit Basilar Artery In Vivo

Abstract

Although cocaine-induced constriction of cerebral vessels may play an important negative role in the pathogenesis of cocaine-related stroke, the mechanism underlying the vasospasm remains unclear. This study investigated the role of endothelin-1 in mediating the spasm. Intracisternal cocaine infusion (10 μl/h via osmotic pump) into the cisterna magna of rabbits induced time- and concentration-dependent spasm. Maximal spasm was achieved with 100 μM cocaine infusate, and was observed as early as 0.5 days and reached a maximum at 2 days. Coinfusion of 100 μM cocaine with the endothelin receptor antagonist PD145065 (100 μM) prevented the spasm. Cerebral spinal fluid levels of cocaine and benzoylecgonine, a major cocaine metabolite, were below the limit of assay detection. This study demonstrates the novel finding that endothelin-1 mediates cocaine-induced cerebral vasospasm.