Cholinergic modulation of the coronary vasoconstriction induced by cocaine in conscious dogs

R. P. Shannon, B. S. Stambler, K. Komamura, T. Ihara, S. F. Vatner

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40 Scopus citations

Abstract

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. Methods and 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 MV̇O2 (49±8%). The increase in coronary vascular resistance was enhanced (p<0.05) in the presence of β-adrenergic receptor blockade (46±8%), whereas the MV̇O2 response was less (28±3%). Again, the addition of cholinergic blockade to β-blockade attenuated the increase in coronary vascular resistance (23±6%) without affecting the increase in MV̇O2 (25±4%). Combined α-, β-, 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 β-adrenergic receptor blockade.

Original languageEnglish (US)
Pages (from-to)939-949
Number of pages11
JournalCirculation
Volume87
Issue number3
DOIs
StatePublished - 1993
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • coronary vascular tone
  • myocardial oxygen tension
  • parasympathetic

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