ABSTRACT
Endothelin is a 21-amino-acid, vasoactive peptide. Sequence analysis of 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. It is one of the most potent endogenous vascular smooth-muscle
constrictors, ten times more potent than angiotensin II, vasopressin, and neuropeptide
Y.
Shortly after the discovery of this vasoconstrictor peptide, it was revealed that
endothelin also possesses vasodilator properties at doses lower than those necessary
to produce vasoconstriction. However, controversy still exists over the mechanism(s)
of action; prostacyclin and endothelium-derived relaxing factor (EDRF) have mainly
been implicated as the source of the initial vasodepressor effect. ET also elicits
markedly different regional hemodynamic response patterns. There is a heterogeneity
in the observed vasodilation or vasoconstriction, depending on species and on vascular
beds studied in the same species.
Endothelin has been implicated in a number of pathologic situations, including tissue
ischemia and vasospasm. ET seems to be produced more actively around the site of endothelial
damage; the loss of balance between its vasodilator- and vasoconstrictor-induced responses
could contribute to its patho-physiologic properties.
Experimental results strongly support the concept that ET could be important in controlling
vascular tonus, both in the healthy and the diseased vessel.
