Human urotensin-II, the most potent mammalian vasoconstrictor identified to date, as a therapeutic target for the management of cardiovascular disease

The novel cyclic undecapeptide human urotensin-II (hU-II) and its high-affi nity G-protein-coupled receptor, GPR14, are both expressed within the human cardiovasculature (vascular smooth muscle, endothelium, myocardium, corona ry atheroma, etc.) and may, therefore, contribute to the (patho)physiologic al regulation of cardiovascular homeostasis in humans. Indeed, hU-II is an efficacious, sustained spasmogen of mammalian isolated blood vessels includ ing those from rats, rabbits, dogs, pigs, non-human primates and humans (wh ere it is one to two orders of magnitude more potent than endothelin (ET)-1 ). In vivo, hU-II markedly alters systemic hemodynamics in the anesthetized primate (up arrow cardiac contractility [dP/dt], up arrow stroke volume, d own arrow total peripheral resistance) ultimately resulting in fatal cardio vascular collapse. As such, the development of selective hU-II receptor ant agonists may be of utility in the management of cardiovascular disorders ch aracterized by aberrant vasoconstriction, myocardial dysfunction and/or car diac remodeling (e.g., myocardial infarction, congestive heart failure). (T rends Cardiovasc Med 2000;10:229-237). (C) 2001, Elsevier Science Inc.