Mechanisms responsible for coronary vasospasm

Abstract

Studies have been conducted on isolated segments of the left circumflex coronary artery of the dog to gain information on the mechanism or mechanisms of vasospasm. Coronary arteries contain both postjunctional alpha1- and beta1-adrenoceptors, and both are accessible to norepinephrine released from the sympathetic nerves. However, owing to the dominance of the beta1-adrenoceptors, sympathetic stimulation causes relaxation of the vascular smooth muscle. In the primary branches of the circumflex artery, only beta1-adrenoceptors are present. In patients with spasm of the coronary arteries, blockade of the beta1-adrenoceptors may aggravate the spasm by permitting the unopposed constrictor action of the sympathetic nerves on the alpha1-adrenoceptors on these vessels. The blood platelets contain substances, including 5-hydroxytryptamine (serotonin) and thromboxane A2, which can cause constriction of vascular smooth muscle. These substances are released whenever platelets aggregate. The normal endothelium, by forming and releasing prostacyclin, inhibits platelet aggregation. In addition, in response to platelet products, the normal endothelium forms one or more inhibitory substances that cause relaxation of the underlying smooth muscle. Also, if any thrombin is formed, this also causes an endothelium-mediated relaxation of the artery. Patients with coronary artery spasm usually have morphologic changes in the artery at the site of the spasm. Thus, platelets can aggregate at the site and the resultant release of serotonin and thromboxane A2, acting directly on the smooth muscle, causes constriction of the artery. Hypoxia of the myocardium follows and this augments the constriction.