Mechanisms of coronary vasospasm: Role of endothelium

Abstract

Studies in recent years have demonstrated that coronary vasospasm (Prinzmetal's Angina) is a consequence of endothelial cell damage. Normal endothelium, in response to increases in shear stress, or to platelet products and other agonists, releases endothelium-derived relaxing factor(s) (EDRF) with resultant vasodilatation. One substance released may be nitric oxide, another a hyperpolarizing factor. In addition EDRF, like prostacyclin, inhibits platelet aggregation. In porcine coronary vessels the amount of EDRF released can be increased by a diet of codliver oil and decreased by a high cholesterol diet. When endothelium is damaged, the absence of EDRF and prostacyclin at the site leads to platelet aggregation with the release, among other substances, of serotonin (5HT) and thromboxane A2. These now act directly on the smooth muscle to cause contraction. In addition some serotonin is taken up by the sympathetic nerve endings and is released as a false transmitter to aggravate the constriction. The resultant hypoxia/anoxia can cause any functional endothelium to release contracting factor(s), further compounding the constriction. Evidence of platelet aggregation in humans is the presence of serotonin in the coronary sinus blood in resting patients with coronary artery disease.