Published Online
on February 11, 2002

A more recent version of this article appeared on March 5, 2002

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Submitted on October 1, 2001
Revised on December 21, 2001
Accepted on December 21, 2001

Mechanism of the Blood Pressure--Raising Effect of Cocaine in Humans

Meryem Tuncel MD, Zhongyun Wang MD, Debbie Arbique RN, Paul J. Fadel PhD, Ronald G. Victor MD, and Wanpen Vongpatanasin MD^*

From the Department of Internal Medicine, Hypertension Division, and Donald W. Reynolds Cardiovascular Clinical Research Center, UT Southwestern Medical Center, Dallas, Tex.

^* To whom correspondence should be addressed. E-mail: wanpen.vongpatanasin{at}utsouthwestern.edu.

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.

Key words: cocaine • norepinephrine • nervous system, sympathetic • baroreceptors

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