The role of central and autonomic neural mechanisms in the cardiovascular effects of cocaine in conscious squirrel monkeys.
The effects of cocaine on cardiovascular function were studied in six conscious squirrel monkeys. Cocaine (0.01-3 mg/kg i.v.) increased mean arterial blood pressure and heart rate (HR) in a dose-dependent manner. The effect of cocaine on HR reached a maximum at 0.3 mg/kg. Doses of cocaine up to 3 mg/kg did not evoke cardiac rhythm disturbances. Pentobarbital or halothane anesthesia attenuated the pressor and tachycardiac effects of 3 mg/kg of cocaine. Antagonism of the pressor response to cocaine by halothane was significantly greater than that by pentobarbital. Halothane, but not pentobarbital, also significantly reduced the pressor response to norepinephrine (1 micrograms/kg i.v.). Blockade of autonomic ganglia by hexamethonium failed to antagonize the pressor and tachycardiac effects of 3 mg/kg of cocaine. The pressor response to 3 mg/kg of cocaine was antagonized by alpha adrenoceptor blockade with phentolamine, whereas the tachycardiac response to cocaine was antagonized by beta adrenoceptor blockade with propranolol. These results suggest that the blood pressure and HR increasing effects of cocaine in conscious squirrel monkeys are not due to stimulation of the central nervous system-sympathoadrenal neural axis, but are due to its peripheral actions on catecholaminergic systems. The 1- and 3-mg/kg doses of cocaine caused an initial reduction in HR of 5 to 30 beats/min in three monkeys and 90 to 110 beats/min in one animal before the onset of their tachycardiac effect. None of the above pharmacological interventions were effective in preventing this initial, moderate reduction in HR in three monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)
Tella
S R
SR
Preclinical Pharmacology Branch, National Institute on Drug Abuse, Baltimore, Maryland.
Schindler
C W
CW
Goldberg
S R
SR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012453:Saimiri; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects*
D006584:Hexamethonium Compounds; D018738:Hexamethonium; D011433:Propranolol; D010424:Pentobarbital; D003042:Cocaine; D006221:Halothane; D010646:Phentolamine