Spasm of the coronary arteries: causes and consequences (the scientist's viewpoint).

Both beta 1- and alpha 1-adrenoceptors are present on canine coronary arteries, and they are accessible to norepinephrine released from the sympathetic nerves. Under normal conditions, these arteries relax because of the predominance of the beta 1-adrenoceptors, whereas constriction prevails in the presence of beta 1-adrenoceptor antagonists. The coronary arteries also have cholinergic nerves. When activated, these nerves release acetylcholine, which acts on muscarinic receptors on the sympathetic nerve terminals to reduce the output of norepinephrine and thereby lessen the relaxation mediated by beta 1-adrenoceptors. Thus, muscarinic agonists can precipitate coronary artery spasm. If the smooth muscle cells of the coronary arteries become hypoxic, their responsiveness to beta-adrenergic stimulation is lost and constrictor responses are exaggerated. Cardiac glycosides prevent the predominance of the beta-adrenergic effects of norepinephrine. Therefore, after treatment with ouabain, release of norepinephrine from the sympathetic nerves leads not to relaxation but to further contraction of coronary arteries. The endothelium of the coronary arteries inhibits platelet aggregation by the formation and release of prostacyclin, and it reacts to platelet products by causing relaxation of the underlying smooth muscle. In addition, if any thrombin is formed, it also causes endothelium-mediated relaxation. If the endothelium is damaged, these protective mechanisms are lost. Patients with coronary artery spasm usually have morphologic changes in the artery at the site of the spasm. Platelets can aggregate at this site and release vasoactive substances, which--aided by formation of thrombin--cause contraction. Thus, the blood supply to the myocardium is reduced; the ensuing hypoxia augments the constriction. Acute myocardial ischemia caused by coronary vasospasm may precipitate acute cardiac rhythm disturbances and sudden death by ventricular tachycardia or fibrillation.