Calcium channel antagonists reduce the cocaine-induced decrease in cardiac output in a subset of rats.
Intravenous (i.v.) cocaine administration elicits a decrease in cardiac output (CO) in some but not all rats. In the present study, we examined the effects of L-type calcium channel antagonists on cardiovascular responses in conscious freely moving rats with a cocaine-induced decrease in CO. Arterial blood pressure (ABP), heart rate (HR), and CO (pulsed Doppler flowmetry) were measured, and estimates of changes in systemic vascular resistance (SVR), stroke volume (SV), and rate-pressure product (RPP) were calculated from these values. After recovery, rats were treated with cocaine (5 mg/kg, i.v.) to ascertain their myocardial responses. Some rats demonstrated a decrease in CO, usually during the peak pressor response after cocaine administration, whereas others experienced only slight increases in CO. Rats demonstrating a minimum 15% decrement in CO were pretreated with either verapamil or nifedipine before cocaine was readministered. Verapamil (150 micrograms/kg) or nifedipine (100 micrograms/kg) selectively reduced the peak fall in CO and the increase in SVR after cocaine administration, whereas nifedipine (25 micrograms/kg) had little effect on these parameters. Neither drug affected the pressor response to cocaine. These data suggest that calcium channel antagonists can selectively reduce cocaine-induced decreases in CO and increases in SVR without reducing afterload in a subset of rats sensitive to the cardiodepressive effects of cocaine.
Knuepfer
M M
MM
Department of Pharmacological and Physiological Science, St. Louis University School of Medicine, Missouri 63104.
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects*; D003042:Cocaine / Q000037:antagonists & inhibitors*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014700:Verapamil; D003042:Cocaine; D009543:Nifedipine