Deletion of the UT receptor gene results in the selective loss of urotensin-II contractile activity in aortae isolated from UT receptor knockout mice

Br J Pharmacol. 2003 May;139(2):464-72. doi: 10.1038/sj.bjp.0705254.


1 Urotensin-II (U-II) is among the most potent mammalian vasoconstrictors identified and may play a role in the aetiology of essential hypertension. Currently, only one mouse U-II receptor (UT) gene has been cloned. It is postulated that this protein is solely responsible for mediating U-II-induced vasoconstriction. 2 This hypothesis has been investigated in the present study, which assessed basal haemodynamics and vascular reactivity to hU-II in wild-type (UT((+/+))) and UT receptor knockout (UT((-/-))) mice. 3 Basal left ventricular end-diastolic and end-systolic volumes/pressures, stroke volumes, mean arterial blood pressures, heart rates, cardiac outputs and ejection fractions in UT((+/+)) mice and in UT((-/-)) mice were similar. 4 Relative to UT((+/+)) mouse isolated thoracic aorta, where hU-II was a potent spasmogen (pEC(50)=8.26+/-0.08) that evoked relatively little vasoconstriction (17+/-2% 60 mM KCl), vessels isolated from UT((-/-)) mice did not respond to hU-II. However, in contrast, the superior mesenteric artery isolated from both the genotypes did not contract in the presence of hU-II. Reactivity to unrelated vasoconstrictors (phenylephrine, endothelin-1, KCl) and endothelium-dependent/independent vasodilator agents (carbachol, sodium nitroprusside) was similar in the aorta and superior mesenteric arteries isolated from both the genotypes. 5 The present study is the first to directly link hU-II-induced vasoconstriction with the UT receptor. Deletion of the UT receptor gene results in loss of hU-II contractile action with no 'nonspecific' alterations in vascular reactivity. However, as might be predicted based on the limited contractile efficacy recorded in vitro, the contribution that hU-II and its receptor make to basal systemic haemodynamics appears to be negligible in this species.

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Body Weight
  • Gene Targeting
  • Genotype
  • Hemodynamics
  • Humans
  • In Vitro Techniques
  • Male
  • Mesenteric Artery, Superior / drug effects
  • Mesenteric Artery, Superior / physiology
  • Mice
  • Mice, Knockout
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology*
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism
  • Urotensins / metabolism*
  • Urotensins / pharmacology
  • Urotensins / physiology
  • Vasoconstriction / drug effects
  • Vasoconstriction / physiology*
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology


  • Receptors, G-Protein-Coupled
  • Urotensins
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • urotensin II