What is the role of endothelial cells in cocaine-induced vasoconstriction?

Updated: Sep 01, 2018
  • Author: Lynn Barkley Burnett, MD, EdD, LLB(c); Chief Editor: Sage W Wiener, MD  more...
  • Print
Answer

Cocaine increases production of the potent vasoconstrictor endothelin, and simultaneously decreases production of nitrous oxide, a powerful vasodilator. As a result of alpha-adrenergic stimulation, cocaine may exert a direct vasoconstrictive effect by increasing the influx of calcium across endothelial cell membranes. These factors may produce coronary artery spasm. Although this may occur even in patients who do not have significant coronary artery disease, spasm is most pronounced in portions of the coronary artery that are already narrowed. Therefore, in patients who do have high-grade obstruction, including patients whose stenoses were previously asymptomatic, coronary artery spasm of even modest degree can have devastating consequences.

In healthy coronary arteries, endothelial cells release endothelium-derived relaxing factor (EDRF) and prostacyclin, which interact synergistically to relax vascular smooth muscle and inhibit platelet adhesion and aggregation. Mild atherosclerosis and hypercholesterolemia impair endothelium-mediated vasodilation in coronary arteries, and animal studies suggest that endothelial dysfunction predisposes a person to vasoconstriction and arterial spasm. Hypersensitivity to the vasoconstrictor effects of catecholamines has also been demonstrated in humans with endothelial dysfunction. Therefore, individuals with mild coronary disease who use cocaine may be predisposed to occlusive vascular spasm at the site of early atherosclerotic lesions.

The combination of intimal hyperplasia, accelerated atherosclerosis, and endothelial dysfunction create a prothrombotic milieu.

Cocaine also potentiates platelet thromboxane production and decreases protein C and antithrombin III production, as well as the production and release of prostacyclin. Aggregating platelets are an important source of serotonin. In patients with dysfunctional endothelium, serotonin causes intense vasoconstriction because of its unopposed effects on vascular smooth muscle.


Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!