Cocaine stimulates the human cardiovascular system via a central mechanism of action.
BACKGROUND
Cocaine is thought to stimulate the cardiovascular system by blocking peripheral norepinephrine reuptake. This study was designed to test the novel hypotheses that cocaine also stimulates the human cardiovascular system by (1) increasing central sympathetic outflow, or (2) decreasing parasympathetic control of heart rate.


RESULTS
In 14 healthy cocaine-naive humans, we measured blood pressure, heart rate, and skin sympathetic nerve activity (SNA) with intraneural microelectrodes before, during, and for 90 minutes after intranasal cocaine (2 mg/kg, n=7) or lidocaine (2 mg/kg, n=7). Intranasal cocaine caused an initial but transient 3. 3-fold increase in skin SNA during the period of intranasal administration followed by a sustained 2.4-fold increase lasting for up to 90 minutes after cocaine. Unlike cocaine, intranasal lidocaine caused only a small transient increase in skin SNA due to local nasal irritation. The cocaine-induced increase in SNA was accompanied by decreased skin blood flow, increased skin vascular resistance, and increased heart rate. In 11 additional subjects, we showed that the cocaine-induced increase in heart rate was eliminated by beta-adrenergic receptor blockade (propranolol) but unaffected by muscarinic receptor blockade (atropine), indicating sympathetic mediation.


CONCLUSIONS
These studies provide direct microneurographic evidence in humans that intranasal cocaine stimulates central sympathetic outflow. This central sympathetic activation appears to be targeted not only to the cutaneous circulation promoting peripheral vasoconstriction but also to the heart promoting tachycardia.
Vongpatanasin
W
W
Divisions of Hypertension and Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Mansour
Y
Y
Chavoshan
B
B
Arbique
D
D
Victor
R G
RG
D000281:Administration, Intranasal; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D002319:Cardiovascular System / Q000187:drug effects* / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D012016:Reference Values; D012867:Skin / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects*; D014838:Volunteers
D000319:Adrenergic beta-Antagonists; D018765:Dopamine Uptake Inhibitors; D018727:Muscarinic Antagonists; D008012:Lidocaine; D003042:Cocaine; D009638:Norepinephrine