TY - JOUR
T1 - Cocaine stimulates the human cardiovascular system via a central mechanism of action
AU - Vongpatanasin, Wanpen
AU - Mansour, Yasser
AU - Chavoshan, Bahman
AU - Arbique, Debbie
AU - Victor, Ronald G.
PY - 1999/8/3
Y1 - 1999/8/3
N2 - 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. Methods and 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 β- 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.
AB - 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. Methods and 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 β- 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.
KW - Cocaine
KW - Microneurography
KW - Nervous system, sympathetic
UR - http://www.scopus.com/inward/record.url?scp=0033520047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033520047&partnerID=8YFLogxK
U2 - 10.1161/01.CIR.100.5.497
DO - 10.1161/01.CIR.100.5.497
M3 - Article
C2 - 10430763
AN - SCOPUS:0033520047
SN - 0009-7322
VL - 100
SP - 497
EP - 502
JO - Circulation
JF - Circulation
IS - 5
ER -