Human urotensin-II is a potent vasoactive peptide: pharmacological characterization in the rat, mouse, dog and primate

J Cardiovasc Pharmacol. 2000 Nov;36(5 Suppl 1):S163-6. doi: 10.1097/00005344-200036051-00051.


The observation that the novel G-protein-coupled receptor (GPCR) GPR14 and its cognate ligand, urotensin-II (U-II), are expressed within the mammalian vasculature raises the possibility that they may influence cardiohemodynamic homeostasis. To this end, this study examined the vasoactive properties of U-II in rodents, dogs and primates. In vitro, human U-II was a sustained vasoconstrictor with a potency (pD2s < or = 9) approximately an order of magnitude greater than that seen with endothelin-1 (ET-1), making it one of the most, if not the most, potent mammalian vasoconstrictor identified to date. However, in vitro responses exhibited significant anatomical and/or species-dependency, that is, human U-II was a selective 'aorto-coronary' vasoconstrictor in rats and dogs, inactive in mice and contracted all primate arteries studied. In vivo, this peptide evoked a complex, dose-dependent hemodynamic response in the anesthetized primate, culminating in severe myocardial depression and fatal circulatory collapse. As such, U-II may represent a novel neurohumoral regulator of mammalian cardiovascular physiology and pathology in particular disorders characterized by aberrant vascular smooth muscle and/or myocardial function.

MeSH terms

  • Animals
  • Dogs
  • Dose-Response Relationship, Drug
  • Hemodynamics / drug effects
  • Humans
  • In Vitro Techniques
  • Macaca fascicularis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Rats
  • Rats, Sprague-Dawley
  • Species Specificity
  • Urotensins / pharmacology*
  • Vasoconstriction / drug effects*


  • Urotensins
  • urotensin II