Cocaine-induced endothelin-1-dependent spasm in rabbit basilar artery in vivo.
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 microl/h via osmotic pump) into the cisterna magna of rabbits induced time- and concentration-dependent spasm. Maximal spasm was achieved with 100 microM cocaine infusate, and was observed as early as 0.5 days and reached a maximum at 2 days. Coinfusion of 100 microM cocaine with the endothelin receptor antagonist PD145065 (100 microM) 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.
Fandino
Javier
J
Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, P. O. Box 670575, Cincinnati, OH 45267-0575, USA.
Sherman
Jonathan D
JD
Zuccarello
Mario
M
Rapoport
Robert M
RM
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D011817:Rabbits; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; C082887:PD 145065; D003042:Cocaine