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 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.

• Authors: Javier Fandino, Jonathan D Sherman, Mario Zuccarello, Robert M Rapoport
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 41 Issue 2 Pg. 158-61 (Feb 2003) ISSN: 0160-2446 [Print] United States
• PMID: 12548074 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Endothelin Receptor Antagonists
• Endothelin-1
• Oligopeptides
• Receptor, Endothelin A
• Receptors, Endothelin
• PD 145065
• Cocaine

Topics

• Animals
• Basilar Artery (drug effects, physiology)
• Cocaine (pharmacology)
• Dose-Response Relationship, Drug
• Endothelin Receptor Antagonists
• Endothelin-1 (antagonists & inhibitors, physiology)
• Male
• Oligopeptides (pharmacology)
• Rabbits
• Receptor, Endothelin A
• Receptors, Endothelin (physiology)
• Vasoconstriction (drug effects, physiology)