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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: M) were generated in the presence or absence of Urantide or Palosuran (1 µM). RESULTS: 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. CONCLUSION: UT antagonism effectively suppresses U-II reactivity through distinct pharmacological profiles, highlighting therapeutic potential in diabetic vasculopathy.