The endothelin system is activated in a number of different cardiovascular diseases. This activation involves the induction of production of endothelin-1 in several different cell types in the heart and in the vascular wall, as well as release into plasma. The increased activity of the endothelin system seems to be deleterious in several situations. The deleterious effects may include enhanced vasoconstriction, mitogenic effects and proinflammatory effects. In such situations, administration of endothelin receptor antagonists may prove useful. The plasma levels of endothe-lin-1 in moderate to severe CHF, atherosclerosis and following acute MI relate to the severity of the disease. Furthermore, high levels of endothelin-1 in patients with CHF and following MI correlate highly significantly with mortality. However, it should also be emphasized that plasma levels of endothelin-1 are usually low and studies in experimental animals indicate that endogenous endothelin-1 may also be of pathophysiological significance even when plasma endothelin-1 levels are low.
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