Local endocrine factors (autacoids, paracrine agents), which are secreted from vessel’s endothelium, provide to arrange of vascular tonus. Some of these factors cause vessel relaxation (vasodilator) such as nitric oxide (NO) and prostaglandin-I₂ (PGI₂); some others cause vessel spasm (vasoconstrictor) such as endothelin (ET)-1 and angiothensin-II. Described in 1988 by Yanagisawa and at al., ET-1 synthesized in vessel endothelium; with its long lasting effect and slow releasing, it is presently one of the strongest vasoconstrictor agents contrary to NO. ET, derived from vessel endothelium is ubiquitous peptide, acts as promitogens and plays an important role during embryonic development. Existence of three distinct genes for ET has been determined which are called ET-1, ET-2, ET-3 and encodes three distinct peptides. However, ET-1 is the isopeptide which is found in greatest concentration in the blood and mainly synthesized by the human endothelium. All three ET isoforms include four cysteine residues, which connect to disulphide bonding (Cys¹-Cys¹⁵; Cys³-Cys¹¹). ET-1, which has twenty-one amino acids residue, realizes biological effects via cell surface ET_A and ET_B reseptors, which are 7-transmembrane receptors coupled to G-proteins. ET receptor antagonists submit a new therapeutic area for serious diseases such as congestive heart failure, pulmonary hypertension, arterial hypertension, prostate hypertrophy, prostate cancers, preeclampsia, atherosclerosis and renal failure.

Keywords: Endothelins, endothelin-1, endothelin receptor antagonists, autacoids