Cholinergic modulation of the coronary vasoconstriction induced by cocaine in conscious dogs.
BACKGROUND
The effects of cocaine on the coronary circulation were examined in conscious dogs chronically instrumented to measure arterial and left ventricular pressures, coronary blood flow, and arterial and coronary sinus oxygen content.


RESULTS
With heart rate held constant, the peak effects of cocaine (1 mg/kg i.v.) occurred within 2 minutes, when mean arterial pressure increased by 42 +/- 5 mm Hg, coronary blood flow increased by 13 +/- 3%, and coronary vascular resistance increased by 24 +/- 3%. The arterial oxygen content increased significantly (by 2.8 +/- 0.3 vol%), the arterial-coronary sinus oxygen difference increased by 2.5 +/- 0.6 vol%, and myocardial oxygen consumption increased by 41 +/- 9%. The increase in coronary vascular resistance induced by cocaine was attenuated (p < 0.05) in the presence of cholinergic blockade (12 +/- 3%) despite a similar increase in MVO2 (49 +/- 8%). The increase in coronary vascular resistance was enhanced (p < 0.05) in the presence of beta-adrenergic receptor blockade (46 +/- 8%), whereas the MVO2 response was less (28 +/- 3%). Again, the addition of cholinergic blockade to beta-blockade attenuated the increase in coronary vascular resistance (23 +/- 6%) without affecting the increase in MVO2 (25 +/- 4%). Combined alpha-, beta-, and cholinergic blockades abolished the systemic hemodynamic and coronary vasoconstrictor response to cocaine.


CONCLUSIONS
In conscious dogs, cocaine induces coronary vasoconstriction, which competes with coronary vasodilator responses to increases in myocardial oxygen consumption. The mechanisms of cocaine's coronary vascular effects are mediated via adrenergic stimulation, and the intensity of the vasoconstrictor effects was reduced significantly by cholinergic blockade, in both the presence and absence of beta-adrenergic receptor blockade.
Shannon
R P
RP
Department of Medicine, Harvard Medical School, Boston, Mass.
Stambler
B S
BS
Komamura
K
K
Ihara
T
T
Vatner
S F
SF
D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
D003042:Cocaine; D009638:Norepinephrine