Background-Cocaine is thought to stimulate the cardiovascular system by blo
cking peripheral norepinephrine reuptake. This study was designed to test t
he novel hypotheses that cocaine also stimulates the human cardiovascular s
ystem by (1) increasing central sympathetic outflow, or (2) decreasing para
sympathetic control of heart rate.
Methods and Results-In 14 healthy cocaine-naive humans, we measured blood p
ressure, heart rate, and skin sympathetic nerve activity (SNA) with intrane
ural microelectrodes before, during, and for 90 minutes after intranasal co
caine (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 o
f intranasal administration followed by a sustained 2.4-fold increase lasti
ng for up to 90 minutes after cocaine. Unlike cocaine, intranasal lidocaine
caused only a small transient increase in skin SNA due to local nasal irri
tation. The cocaine-induced increase in SNA was accompanied by decreased sk
in blood flow, increased skin vascular resistance, and increased heart rate
. In 11 additional subjects, we, showed that the cocaine-induced increase i
n heart rate was eliminated by beta-adrenergic receptor blockade (propranol
ol) but unaffected by muscarinic receptor blockade (atropine), indicating s
ympathetic mediation.
Conclusions-These studies provide direct microneurographic evidence in huma
ns that intranasal cocaine stimulates central sympathetic outflow. This cen
tral sympathetic activation appears to be targeted not only to the cutaneou
s circulation promoting peripheral vasoconstriction but also to the heart p
romoting tachycardia.