ENDOTHELIN - AN ENDOTHELIUM-DERIVED VASOACTIVE PEPTIDE

Endothelin is a 21-amino-acid, vasoactive peptide. Sequence analysis o f cloned cDNAs for porcine and human endothelin precursors showed that endothelin-1 (ET-1) is produced in the endothelial cells. The peptide , endothelin (ET), was first identified as a potent vasoconstrictor. I t is one of the most potent endogenous vascular smooth-muscle constric tors, ten times more potent than angiotensin II, vasopressin, and neur opeptide Y. Shortly after the discovery of this vasoconstrictor peptid e, it was revealed that endothelin also possesses vasodilator properti es at doses lower than those necessary to produce vasoconstriction. Ho wever, controversy still exists over the mechanism(s) of action; prost acyclin and endothelium-derived relaxing factor (EDRF) have mainly bee n implicated as the source of the initial vasodepressor effect. ET als o elicits markedly different regional hemodynamic response patterns. T here is a heterogeneity in the observed vasodilation or vasoconstricti on, depending on species and on vascular beds studied in the same spec ies. Endothelin has been implicated in a number of pathologic situatio ns, including tissue ischemia and vasospasm. ET seems to be produced m ore actively around the site of endothelial damage; the loss of balanc e between its vasodilator- and vasoconstrictor-induced responses could contribute to its pathophysiologic properties. Experimental results s trongly support the concept that ET could be important in controlling vascular tonus, both in the healthy and the diseased vessel.