Endothelin-1 and the regulation of vascular tone

Clin Exp Pharmacol Physiol. 1995 May;22(5):315-23. doi: 10.1111/j.1440-1681.1995.tb02008.x.


1. In 1988, Yanagisawa et al. reported the presence of a potent peptide from the supernatant of porcine endothelial cells. This was later named endothelin-1 (ET-1) and was found to belong to a new family of vasoconstrictor peptides. There are at least three isoforms of endothelin: ET-1, endothelin-2 and endothelin-3. 2. ET-1 is produced from a larger precursor molecule by endothelin converting enzyme (ECE); there may be a number of ECE but the most physiologically relevant appears to be a membrane-bound neutral metalloprotease. The endothelin precursor is produced on demand and is regulated at the mRNA level. 3. Two subtypes of mammalian endothelin receptors have been cloned and sequenced: ETA receptors which mediate vasoconstriction and ETB receptors which mediate both vasoconstriction and vasodilatation. However, functional studies have indicated that other subtypes of endothelin receptors may exist. 4. ET-1 has a wide range of biological actions apart from its direct effects on vascular tone, including constriction of non-vascular smooth muscle, cardiac effects, mitogenesis and stimulation of the release of hormones such as atrial natriuretic peptide and prostacyclin. At low concentrations which have no direct vasoconstrictor action, ET-1 potentiates the effect of other vasoconstrictor agonists. 5. The precise role of ET-1 in health and disease is not well defined at present; however, there are indications that it may have a role in the pathogenesis of some cardiovascular disease states, including subarachnoid haemorrhage, renal ischaemia and certain types of hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cardiovascular Diseases / etiology
  • Endothelin Receptor Antagonists*
  • Endothelins / chemistry
  • Endothelins / pharmacology
  • Endothelins / physiology*
  • Molecular Sequence Data
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects*
  • Receptors, Endothelin / agonists*
  • Signal Transduction / drug effects
  • Vasoconstriction / drug effects


  • Endothelin Receptor Antagonists
  • Endothelins
  • Receptors, Endothelin