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

Article

关键词: INTRANASAL COCAINE;    HEART;    ABUSE;   

DOI  :  10.1161/hc0902.104714

来源: SCIE

【 摘 要 】

Background-Although the sympathomimetic actions and cardiovascular complications of cocaine W-e ascribed to inhibition of norepinephrine (NE) reuptake. this hypothesis has not been tested ill 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 or cocaine. Methods and Results-In 15 healthy cocaine-naive subjects, we measured blood pressure, forearm blood flow, and forearm venous NE concentration during administration or (a) intrabrachial cocaine (0.15 and 15 mg), which produced no systemic neurohormonal effects, and (b) intranasal cocaine (2 mg/k a). 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 b 0.15 mg of intrabrachial cocaine, venous NE concentration was unchanged as sympathetic nerve activity (SNA) decreased reflexively as the result of all 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.

【 授权许可】

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