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Abstract

Cocaine has long been assumed to raise blood pressure (BP) by blocking norepinephrine (NE) reuptake in sympathetic nerve terminals, resulting in alpha-adrenergic vasoconstriction in the peripheral circulation. However, this assumption has not been tested directly in humans, and our recent work indicates that intranasal cocaine acts centrally to increase sympathetic nerve activity (SNA) to the heart and skin while decreasing SNA to skeletal muscle, the latter due to baroreflex activation attendant to the cocaine-induced rise in BP. To isolate the putative effects of cocaine on the NE transporter, in 7 healthy subjects we measured forearm blood flow in both arms (plethysmography), skin blood flow (laser Doppler), and forearm venous [NE] during infusion of cocaine (0.01mg/min) into the left brachial artery. Close arterial infusion of cocaine increased (p < 0.05) local [NE] from 125±20 to 257±96 pg/ml, forearm resistance from 33±2 to 63±12 units, and increased skin vascular resistance by 20±4%, without affecting systemic BP or NE or vascular resistance in the control arm. To determine if such peripheral vasoconstriction explains the BP-raising effect of cocaine, in the same subjects we repeated these measurements during intranasal cocaine, using a dose (2 mg/kg) that increased mean BP by 11±3 mm Hg and produced the same forearm venous cocaine concentration as with brachial artery infusion. With intranasal cocaine, forearm resistance did not increase but surprisingly decreased by 25±4% (p < 0.01). This vasodilator response is: (a) specific for cocaine because it was not seen when BP was increased similarly with i.v. NE; and (b) due to baroreflex-mediated sympathoinhibition in skeletal muscle because intranasal cocaine simultaneously increased vascular resistance in forearm skin, a vascular bed that is not under baroreflex control. We conclude that, although cocaine can inhibit the NE transporter in the human peripheral circulation, this mechanism does not contribute importantly to the BP-raising effect of intranasal cocaine. Because arterial baroreflexes are critical in buffering the vasoconstrictor and hypertensive actions of cocaine, we speculate that patients with defective baroreceptor reflexes are at especially high risk to suffer hypertensive crisis and other catastrophic cardiovascular complications from cocaine.

vasoconstriction, norepinephrine, cocaine
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© American Journal of Hypertension, Ltd. 2001
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