Mechanism of the blood pressure--raising effect of cocaine in humans
by
Tuncel M, Wang Z, Arbique D, Fadel PJ, Victor RG, Vongpatanasin W.
Department of Internal Medicine, Hypertension Division,
and
Donald W. Reynolds Cardiovascular Clinical Research Center,
UT Southwestern Medical Center,
Dallas, TX 75390-8586, USA.
Circulation 2002 Mar 5;105(9):1054-93
ABSTRACTBACKGROUND: 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.Cocaine hotspots
Dopaminergic flies?
Dopaminergic agents
Cocaine immunization
GBR12909 and the rat
The coke-craving brain
Cocaine and depression
Is the dollar based on coke?01 02 03 04 05 06 07 08 09 10 11 12
13 14 15 16 17 18 19 20 21 22 23 24
Refs
HOME
HedWeb
cannabis-marijuana.com
Future Opioids
BLTC Research
Wirehead Hedonism
Paradise-Engineering
Utopian Pharmacology
The Hedonistic Imperative
When Is It Best to Take Crack Cocaine?
The Good Drug Guide
The Responsible Parent's Guide To
Healthy Mood Boosters For All The Family
