Cocaine potentiates the blood pressure and cerebral blood flow response to norepinephrine in rats.
Acute drug-induced hypertension is known to have adverse consequences on the cerebral vasculature. Cocaine abuse has been reported to be associated with an increased frequency of hemorrhagic or ischemic stroke. The purpose of this study was to determine whether cocaine alters the blood pressure or cerebral blood flow response to exogenous norepinephrine. A craniectomy was made over the parietal cortex in rats and cortical blood flow changes were measured using laser-Doppler flowmetry. Ten minutes after cocaine (1 mg/kg, i.v.) or saline, increasing doses of norepinephrine (0.01-10 micrograms/kg, i.v.) were given by bolus injection and changes in blood pressure and flow were monitored. Cocaine produced a transient 27 +/- 5% increase in blood pressure and a 38 +/- 9% increase in blood flow. Cocaine significantly potentiated the blood pressure and cerebral blood flow responses produced by submaximal pressor doses of norepinephrine (0.01-0.6 microgram/kg, i.v.). In summary, cocaine causes a rapid, transient increase in blood pressure and cortical blood flow and potentiates the magnitude and duration of the pressure and flow response to norepinephrine. Repetitive blood pressure elevations in cocaine abusers is one of the proposed mechanisms leading to damage of cerebral vessels. These results may be relevant to an increased frequency of cerebrovascular accidents in cocaine-abusing individuals.
Muir
J K
JK
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Ellis
E F
EF
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007275:Injections, Intravenous; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003042:Cocaine; D009638:Norepinephrine