Mechanism of the blood pressure-raising effect of cocaine in humans

Meryem Tuncel, Zhongyun Wang, Debbie Arbique, Paul J. Fadel, Ronald G. Victor, Wanpen Vongpatanasin

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1054-1059
Number of pages6
JournalCirculation
Volume105
Issue number9
DOIs
StatePublished - Mar 5 2002

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Cocaine
Blood Pressure
Norepinephrine
Forearm
Baroreflex
Vasoconstriction
Sympathomimetics
Nitroprusside
Vascular Resistance

Keywords

  • Baroreceptors
  • Cocaine
  • Nervous system
  • Norepinephrine
  • Sympathetic

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Tuncel, M., Wang, Z., Arbique, D., Fadel, P. J., Victor, R. G., & Vongpatanasin, W. (2002). Mechanism of the blood pressure-raising effect of cocaine in humans. Circulation, 105(9), 1054-1059. https://doi.org/10.1161/hc0902.104714

Mechanism of the blood pressure-raising effect of cocaine in humans. / Tuncel, Meryem; Wang, Zhongyun; Arbique, Debbie; Fadel, Paul J.; Victor, Ronald G.; Vongpatanasin, Wanpen.

In: Circulation, Vol. 105, No. 9, 05.03.2002, p. 1054-1059.

Research output: Contribution to journalArticle

Tuncel, M, Wang, Z, Arbique, D, Fadel, PJ, Victor, RG & Vongpatanasin, W 2002, 'Mechanism of the blood pressure-raising effect of cocaine in humans', Circulation, vol. 105, no. 9, pp. 1054-1059. https://doi.org/10.1161/hc0902.104714
Tuncel, Meryem ; Wang, Zhongyun ; Arbique, Debbie ; Fadel, Paul J. ; Victor, Ronald G. ; Vongpatanasin, Wanpen. / Mechanism of the blood pressure-raising effect of cocaine in humans. In: Circulation. 2002 ; Vol. 105, No. 9. pp. 1054-1059.
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AU - Vongpatanasin, Wanpen

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AB - 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.

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