Document Detail

Mechanism of the blood pressure--raising effect of cocaine in humans.
MedLine Citation:
PMID:  11877354     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Although the sympathomimetic actions and cardiovascular complications of cocaine are ascribed to inhibition of norepinephrine (NE) reuptake, this hypothesis has not been tested in humans. We asked (a) whether cocaine can inhibit NE reuptake in the human peripheral circulation and (b) whether the NE-mediated peripheral vasoconstriction is the main mechanism mediating blood pressure-raising effect of cocaine. METHODS AND RESULTS: In 15 healthy cocaine-naive subjects, we measured blood pressure, forearm blood flow, and forearm venous NE concentration during administration of (a) intrabrachial cocaine (0.15 and 15 mg), which produced no systemic neurohormonal effects, and (b) intranasal cocaine (2 mg/kg). Intrabrachial cocaine (0.15 mg) increased venous forearm NE concentration by 82% and vascular resistance by 71% (P<0.01). Increasing the intrabrachial cocaine dose by 100-fold to match the venous cocaine level of massive cocaine overdose caused a small additional increase in venous forearm NE concentration without causing significant additional vasoconstriction. Although intranasal cocaine (2 mg/kg) matched the venous cocaine concentrations caused by 0.15 mg of intrabrachial cocaine, venous NE concentration was unchanged as sympathetic nerve activity (SNA) decreased reflexively as the result of an increase in blood pressure. When SNA was restored to baseline by blunting the cocaine-induced rise in blood pressure (baroreflex activation) with nitroprusside, venous NE concentration increased to the same level caused by intrabrachial cocaine. CONCLUSIONS: In healthy cocaine-naive individuals, cocaine can inhibit NE reuptake in the human peripheral circulation. However, this mechanism does not contribute importantly to the blood pressure-raising effect of cocaine because activation of baroreceptor reflexes decreases SNA, the neural stimulus for NE release.
Meryem Tuncel; Zhongyun Wang; Debbie Arbique; Paul J Fadel; Ronald G Victor; Wanpen Vongpatanasin
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  105     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Mar 
Date Detail:
Created Date:  2002-03-05     Completed Date:  2002-03-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1054-9     Citation Subset:  AIM; IM    
Department of Internal Medicine, Hypertension Division, and Donald W. Reynolds Cardiovascular Clinical Research Center, UT Southwestern Medical Center, Dallas, TX 75390-8586, USA.
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MeSH Terms
Administration, Intranasal
Baroreflex / drug effects*,  physiology
Blood Flow Velocity / drug effects
Blood Pressure / drug effects*,  physiology
Brachial Artery / drug effects,  physiology
Cocaine / administration & dosage*
Dose-Response Relationship, Drug
Forearm / blood supply
Infusions, Intra-Arterial
Nitroprusside / pharmacology
Norepinephrine / blood*
Sympathetic Nervous System / drug effects*,  physiology
Vascular Resistance / drug effects,  physiology
Vasoconstriction / drug effects,  physiology
Veins / physiology
Grant Support
Reg. No./Substance:
15078-28-1/Nitroprusside; 50-36-2/Cocaine; 51-41-2/Norepinephrine

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