CARDIOVASCULAR EFFECTS OF COCAINE IN CONSCIOUS DOGS - IMPORTANCE OF FULLY FUNCTIONAL AUTONOMIC AND CENTRAL NERVOUS SYSTEMS

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Abstract
The cardiovascular effects of i.v. cocaine were studied in conscious dogs with chronically implanted arterial and venous catheters. The effects of i.v. cocaine on arterial blood pressure, heart rate and rate-pressure product were studied at doses ranging from 0.063 to 8 mg/kg. To avoid any possibility that development of acute tolerance to the actions of cocaine might interfere with our results, each dose of cocaine was administered on a separate day. Cocaine-induced changes in mean arterial blood pressure ranged from an increase of 11.8 .+-. 2.1 mmHg at a dose of 0.063 mg/kg to an increase of 95.8 .+-. 11 mmHg at a dose of 8 mg/kg. Similarly, cocaine-induced changes in heart rate ranged from a decrease of 4.5 .+-. 0.9 beats/min to an increase of 83 .+-. 10 beats/min at the 0.063 and 8 mg/kg cocaine doses, respectively. Although the rate-pressure product was not significantly altered by doses of cocaine below 0.25 mg/kg, doses above that level produced dose-dependent increases in this parameter. The rate-pressure product, which was increased approximately 27% by the 0.25 mg/kg dose of cocaine, was more than doubled by the 2 mg/kg cocaine dose and was increased almost 4-fold by the 8 mg/kg dose of cocaine. The blood pressure response observed after cocaine administration was significantly decreased by pretreatment with 10 mg/kg hexamethonium. In conscious dogs without any pretreatment a 2 mg/kg i.v. dose of cocaine increased mean blood pressure 64.2 .+-. 3.8, but when this dose was administered to the same dogs on a different day after pretreatment with hexamethonium, mean blood pressure only increased 25.3 .+-. 3.4 mmHg. Similarly, anesthesia with pentobarbital virtually abolished the pressor response to cocaine observed in the same dogs on a different day when they were conscious. A cocaine dose of 1 mg/kg, when administered to conscious dogs, increased when blood pressure 45.8 .+-. 5.2 mmHg. This same dose, when administered 30 min after these same dogs were anesthetized with 32 mg/kg pentobarbital sodium on a different day, increased blood pressure only 9.5 .+-. 3.9 mmHg. Thus, cocaine produces dose-dependent cardiovascular effects over a wide range of doses, and its cardiovascular actions, which include an important central nervous system component, are expressed fully only when its integrated peripheral and central nervous system actions are not altered by anesthesia or autonomic antagonists.