MECHANISMS OF HEMODYNAMIC-RESPONSES TO COCAINE IN CONSCIOUS RATS

Several agents have been used to treat cocaine-related cardiovascular complications and toxicity occurring in sensitive individuals, yet the causes of hemodynamic responsiveness and differential sensitivity to cocaine are unknown. In this study, we sought to examine the role of d ifferent mediators in a model of variable cardiovascular responses to cocaine. As noted previously in conscious rats, cardiac output (CO) an d systemic vascular resistance (SVR) responses to cocaine (5 mg/kg, i. v.) varied widely. Twenty of 34 rats exhibited cocaine-induced decreas es in CO of greater than or equal to 8% and large increases in SVR (de signated vascular responders). The remaining rats with little change o r an increase in CO and smaller increases in SVR were named mixed resp onders. Pretreatment with propranolol (1 mg/kg) or metoprolol (1 mg/kg ) reduced heart rate. In mixed responders, propranolol or metoprolol r eversed the cocaine-induced increase in CO and stroke volume and enhan ced the increase in SVR, making these rats respond like vascular respo nders. Nicardipine (25 mu g/kg) reduced the presser response and selec tively reversed the CO responses in vascular responders. N-omega-nitro -L-arginine methyl ester (L-NAME; 2.7 mg/kg) increased arterial pressu re by increasing SVR. Cocaine induced greater presser and SVR response s apparently because of a shift in baseline values elicited by L-NAME alone. Therefore, differences in hemodynamic responses patterns may be the result of differences in beta-adrenergic activation or subsequent calcium channel activation or both. We predict that calcium channel a ntagonists may be useful to treat cocaine-induced cardiovascular compl ications, whereas beta-adrenergic antagonists are not likely to be ben eficial.