Key result
UT receptor deletion in mice abolishes urotensin-II aortic contractility without altering basal systemic hemodynamics.
Why the study?
It is postulated that the UT receptor protein is solely responsible for mediating U-II-induced vasoconstriction, but this has not been directly tested.
Deletion of the UT receptor gene in mice abolishes urotensin-II-induced vasoconstriction without altering basal systemic hemodynamics or non-specific vascular reactivity.
UT receptor deletion selectively abolishes urotensin-II vasoconstriction in mice; hypothesis-generating and leaves open human therapeutic relevance.
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.
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Behm et al. (2003) studied this question. UT receptor gene deletion (UT-/-) vs. Wild-type (UT+/+) mice was evaluated on Basal hemodynamics and vascular reactivity to hU-II. Deletion of the UT receptor gene in mice resulted in the selective loss of urotensin-II contractile activity in isolated aortae without altering basal systemic hemodynamics.
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