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Cocaine-induced endothelin-1-dependent spasm in rabbit basilar artery in vivo.

Authors
Type
Published Article
Journal
Journal of Cardiovascular Pharmacology
0160-2446
Publisher
Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins
Publication Date
Volume
41
Issue
2
Pages
158–161
Identifiers
PMID: 12548074
Source
Medline

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 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.

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