Therapeutic targets in hypertension: Is there a place for antagonists of the most potent vasoconstrictors?

Background: Endothelin-1 (ET-1) and urotensin II (U-II) are the most potent and unusually long-lasting constrictors of human vessels known to date. Objective: In this review, we focus on the vascular effects of endothelin-1 (ET-1) and urotensin II (U-II) and their role in the pathophysiology of hypertension. Results and conclusion: Unlike ET-1, which uniformly constricts most blood vessels, the vasoactive effects of U-II depend both on the species, vascular bed and vessel calibre. Both ET-1 and U-II have potent mitogenic, pro-inflammatory and pro-oxidative properties, which have been implicated in the pathogenesis of human cardiovascular and renal diseases. The availability of highly effective peptide and non-peptide antagonists both for ET-1 and U-II receptors has revealed a role for these potent vasoconstrictor peptides in human (patho)physiology.