PT  - JOURNAL ARTICLE
AU  - L F Jones
AU  - R L Tackett
TI  - Chronic cocaine treatment enhances the responsiveness of the left anterior descending coronary artery and the femoral artery to vasoactive substances.
DP  - 1990 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1366--1370
VI  - 255
IP  - 3
4099  - http://jpet.aspetjournals.org/content/255/3/1366.short
4100  - http://jpet.aspetjournals.org/content/255/3/1366.full
SO  - J Pharmacol Exp Ther1990 Dec 01; 255
AB  - 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.