Endothelin (ET) is a peptide synthetized by endothelial cells (EC), smooth-muscle cells (SMC), cardiomyocytes and endocardial cells in response to the effects of mechanical factors and some biologically active substances--angiotensin 11, interleykin-1, the transforming growth factor-alpha and tumor necrosis factor alpha(TNF-alpha). ET possesses significant constrictor action on vessels (100 times more than angiotensin), positive inotropic action on the heart and stimulates proliferation. Increase of the endogenous endothelin concentration has been shown in many pathological states of the cardiovascular system. By inhibiting ET receptors it has been proved EN involvement in the pathogenesis of some of these states--systemic hypertension, myocardial infarction, vasospasm and cardiac failure.
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