Urotensin II and the kidney

Urotensin II (UTS2), the most potent vasoconstrictor identified thus far, is an undecapeptide hormone with a structure that is highly conserved through mammalian phylogeny. In spite of its broad expression across the invertebrate and vertebrate world, the precise role of UTS2 in physiology and disease is still unknown. The first description of human UTS2 and its receptor brought initial promise of a potential therapeutic target for progressive renal disease, with vasoconstrictive and profibrotic actions within an autocrine and paracrine system and local renal generation that was upregulated with renal pathology.

However, the last decade has not brought the successful development of new treatments first hoped for, with one small human clinical trial bearing negative results. What has become apparent is that the spectrum of actions of UTS2 is broad and often paradoxical. This ancient hormone has both vasoconstrictor and vasodilatory actions, has both profibrotic and antiapoptotic activity, as well as actions which are highly contextual on the particular vascular bed studied and on the presence or absence of superimposed disease state.

With current development of newer UTS2 antagonists attempting to more closely replicate the ligand-receptor kinetics of UTS2 and its receptor, the focus on potential clinical applications of UTS2 inhibition has moved away from the kidney to the treatment of chronic lung and cardiovascular diseases.