[Endothelins and ischemic heart disease]

Endothelins (ET) comprise a group of substances which are produced and have a regulatory function in different systems of the organism. The main cardiovascular ET is ET-1 which is so far the most potent vasoconstrictor substance. ET is important in the early stages of atherosclerosis as it is a strong chemical attractant of monocytes and macrophages and causes endothelial and vasomotor dysfunction. In later stages of atherosclerosis it can affect the firmness and integrity of the fibrous part of the atherosclerotic plaque. During myocardial infarction the ET level rises and this leads to vasoconstriction and reduction of the fibrillation threshold. In coronary angioplasty (PTCA) the ET-1 level rises depending on the applied mechanical stress. ET can participate in the formation of the neointima and the development of restenosis. ET increases also immediately after an aortocoronary bypass (CABG) and after reperfusion. Higher ET levels were found in patients with a positive ECG and echocardiographic loading test. In the latter after CABG normalization of ET was found. Raised ET levels were recorded also in patients where a coronary vasospasm can be provoked, in Prinzmetal's angina pectoris, coronary syndrome X, atrial tachystimulation. In unstable angina pectoris big-ET is elevated, the increase of the ET-1 level is not unequivocal. Stable angina pectoris does not affect ET-1. In the treatment of atherosclerosis for the selective ETA blocker reduction of the number and size of macrophage and foam cells was proved. In acute myocardial infarction a favourable effect for the non-selective ETA/ETB blocker and for the selective ETA blocker was found. In the treatment of restenosis after PTCA blockers of selective ETB receptors and inhibitors of endothelin converting enzyme seem hopeful. Th non-selective ETA/ETB blocker bosentan is in the stage of clinical tests and seems to be safe and perspective.