Vasoactive mediators released by endothelins

Abstract

The endothelins (ETs) constitute a family of potent vasoconstrictor peptides initially isolated and characterized from the supernatant of cultured porcine aortic endothelial cells (EC) by Masaki and colleagues [1]. ETs bear striking structural similarities to the sarafotoxins, which are potent cardiotoxic peptides described from the venom of the burrowing asp Atractaspis enggadensis (see [2, 3]) . Currently, four ET isopeptides are recognized : endothelin-1 (originally porcine/human ET, ET-1), endothelin-2 (ET-2), endothelin-3 (originally rat ET, ET-3) and the more recently identified vasointestinal contractor (VIC) [4, 5] . All ETs possess 21 amino acid residues and two disulfide bonds but differ in their amino acid sequences (Fig . 1) . In vivo, ETs generally produce a biphasic systemic blood pressure response consisting of a brief vasodilation followed by a long-lasting pressor activity 11, 4, 61 . This biphasic systemic response appears to be species and peptide dependent, e .g. prominent vasodilation in cats [7] and is not observed when the peptides are given by infusion [8-11] . A biphasic response is also observed in preparations such as the isolated rat mesentery [12] and the blood perfused dog liver [13] . Early studies pointed to the capacity of ETs to induce the release of vasorelaxing (endothelium-derived nitric oxide, EDNO, and prostacyclin, PGI 2 ) and vasocontracting (thromboxane A 2 , TXA2) substances from isolated perfused organs and it was suggested that such factors may be of importance in modulating the pressor activity of ETs in vivo [6] . The present article considers the vasoactive mediators which modulate the cardiovascular actions of the ETs .