Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans
Central sympatholysis as a novel countermeasure for cocaine-induced sympathetic activation and vasoconstriction in humans
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DOI：
10.1016/j.jacc.2007.03.060
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发表时间：
2007-08-14
影响因子：
24
通讯作者：
Vongpatanasin, Wanpen
中科院分区：
文献类型：
--
作者：
Menon, Dileep V.;Wang, Zhongyun;Vongpatanasin, Wanpen
Objectives The aim of this study was to determine whether cocaine's sympathomimetic actions can be reversed by a potent centrally acting alpha 2 adrenergic receptor (AR) agonist (dexmedetomidine).Background We recently showed that cocaine stimulates the human cardiovascular system primarily by acting in the brain to increase sympathetic nerve activity (SNA), the neural stimulus to norepinephrine release. Thus, SNA constitutes a putative new drug target to block cocaine's adverse cardiovascular effects at their origin.Methods In 22 healthy cocaine-naive humans, we measured skin SNA (microneurography) and skin blood flow (laser Doppler velocimetry) as well as heart rate and blood pressure before and after intranasal cocaine (2 mg/kg) alone and in combination with dexmedetomidine or saline.Results During intranasal cocaine alone, SNA increased by 2-fold and skin vascular resistance increased from 13.2 +/- 2.3 to 20.1 +/- 2.2 resistance units while mean arterial pressure increased by 14 3 mm Hg and heart rate by 18 +/- 3 beats/min (p < 0.01). Dexmedetomidine abolished these increases, whereas intravenous saline was without effect. Dexmedetomidine was effective in blocking these sympathomimetic actions of cocaine even in all 7 subjects who were homozygous for the Del322-325 polymorphism in the alpha 2C AR, a loss-of-function mutation that is highly enriched in blacks.Conclusions The data advance the novel hypothesis that central sympatholysis with dexmedetomidine constitutes a highly effective countermeasure for cocaine's sympathomimetic actions on the human cardiovascular system, even in individuals carrying the alpha 2CDel322-325 polymorphism. (Study to Improve Scientific Understanding of the Cardiovascular Actions of Cocaine; http://clinicaltrials.gov/ct/show/NCT00338546?order=1; NCT00338546) (J Am Coll Cardiol 2007;50:626-33) (c) 2007 by the American College of Cardiology Foundation.
