[Endothelin--an important factor in coronary heart disease].

The peptide hormone endothelin was initially discovered in endothelial cells. However, it has recently been shown that endothelin is produced by cardiomyocytes too. Endothelin is the most potent of all known vasoconstrictors. The coronary circulation is highly sensitive to endothelin, and intracoronary infusion may lead to lethal coronary spasm. Patients with variant angina pectoris have a higher plasma concentration of endothelin. Moreover, exposure to cold leads to a further increase in endothelin. Therefore increased production of endothelin may be an important mediator of vasospasm. Acute myocardial infarction is followed by an increase in circulating endothelin. Remaining high endothelin levels after myocardial infarction are associated with poor prognosis. Cardiomyocytes increase their production of endothelin during ischemia, and this increase may be harmful, either through an effect on the coronary circulation or by acting directly on the cardiomyocytes. Blockade of endothelin receptors has been shown to reduce the size of an infarction. Thus, intense research is directed towards discovering therapeutical agents that either inhibit production or block the effects of endothelin. Recently, an orally active endothelin receptor antagonist was discovered, and clinically useful therapeutical agents will most probably be available in the near future.