Cocaine stimulates the human cardiovascular system via a central mechanismof action

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.