Chronic cocaine treatment enhances the responsiveness of the left anterior descending coronary artery and the femoral artery to vasoactive substances.
The mechanism by which cocaine produces sudden cardiac death has not been elucidated, but clinical evidence indicates that it may be due to a direct or indirect action on coronary vessels. The present study was designed to compare the responses of the isolated left anterior descending (LAD) coronary artery and femoral artery taken from untreated dogs with the response of these vessels taken from dogs administered cocaine (1 mg/kg i.v.) daily for 4 weeks. The actions of norepinephrine, U-46619 (a thromboxane A2 analog) and serotonin (5-HT) were evaluated. The direct vascular action of cocaine was also determined. Morphology of the blood vessels was evaluated by scanning electron microscopy. Chronic cocaine treatment significantly increased the sensitivity and maximum response of the femoral artery to norepinephrine, U-46619 and 5-HT. The sensitivity of the LAD coronary artery to U-46619 and 5-HT and the maximum response to U-46619 and 5-HT were also enhanced. Vasoconstriction produced by cocaine was not dose dependent and only occurred at high concentrations (10(-5)-10(-4) M). Morphology of the vessels was evaluated by scanning electron microscopy. Femoral arteries from cocaine-treated dogs exhibited loss of endothelial integrity, areas of excessive endothelial cell sloughing and thrombus formation. LAD coronary arteries exhibited only areas of enhanced endothelial cell sloughing. The results of this study indicate that the femoral artery and the LAD coronary artery are more sensitive to endogenous vasoactive substances after chronic cocaine use, which may result in enhanced peripheral vasoconstriction and cardiac ischemia. Morphological results demonstrate femoral arterial thrombosis associated with cocaine use.
Jones
L F
LF
Cardiovascular Pharmacodynamics Laboratory, College of Pharmacy, University of Georgia, Athens.
Tackett
R L
RL
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003331:Coronary Vessels / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D005263:Femoral Artery / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008855:Microscopy, Electron, Scanning; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D011450:Prostaglandin Endoperoxides, Synthetic; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003042:Cocaine; D009638:Norepinephrine