Role of selective U-II receptor antagonists in modifying vascular function in intact and denuded aortic diabetic rats

Urotensin-II (U-II) is a potent vasoconstrictor acting via UT receptors. Endothelial buffering normally restrains U-II signaling, but this protection is diminished in diabetes mellitus, contributing to vascular dysfunction. Selective UT antagonists such as Urantide (peptidic) and Palosuran (non-peptidic) are promising, yet direct comparisons under diabetic conditions remain limited.

To assess the effects of Urantide and Palosuran on U-II-induced vasoconstriction in aortae from non-diabetic and diabetic rats with intact and denuded endothelium.

Thoracic aortic rings were mounted for isometric recording. Concentration-response curves to U-II (${10}^{-11}$-${10}^{-8}$ M) were generated in the presence or absence of Urantide or Palosuran (1 µM).

Endothelial loss nearly doubled U-II contractions in non-diabetic aorta and unmasked hyperreactivity in diabetic vessels. Urantide abolished efficacy, while Palosuran attenuated both efficacy and potency, with pronounced inhibition in diabetic denuded rings.

UT antagonism effectively suppresses U-II reactivity through distinct pharmacological profiles, highlighting therapeutic potential in diabetic vasculopathy.