Role of cardiac nerves in the cardiovascular response to cocaine in conscious dogs

Background-Although the cardiovascular toxicity of cocaine is well recogniz ed, considerable controversy remains as to the relative contribution of loc al norepinephrine reuptake inhibition versus central stimulatory effects of cocaine in eliciting its cardiovascular actions. The purpose of the presen t study was to determine the role of cardiac nerves in mediating the left v entricular (LV) and coronary hemodynamic responses to cocaine. Methods and Results-We studied the cardiovascular response to acute cocaine administration (1 mg/kg) in 10 intact, conscious dogs and 6 dogs with vent ricular denervation (VD). There were no significant differences in baseline hemodynamic parameters or plasma catecholamines between the 2 groups. In r esponse to acute cocaine, LV and coronary hemodynamic responses were enhanc ed in the VD dogs. The enhanced systemic presser and heart rate responses i n VD dogs suggest that cardiac nerves mitigate the response to cocaine thro ugh ventricular mechanoreceptors rather than mediating the responses. Conclusions-These data suggest that peripheral blockade of norepinephrine r euptake is not the principal mechanism of the acute cardiac effects of coca ine. Rather, cardiac nerves modulate the effects of cocaine through baroref lex mechanisms. Thus, individual differences in baroreflex sensitivity may explain the hemodynamic variability observed in response to cocaine.