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Human Urotensin-II is a Potent Vasoactive Peptide

2000; Lippincott Williams & Wilkins; Volume: 36; Issue: Supplement 1 Linguagem: Inglês

10.1097/00005344-200036051-00051

1533-4023

Stephen A. Douglas, Daryl J. Ashton, Charles F. Sauermelch, Robert W. Coatney, Derek H. Ohlstein, Michael R. Ruffolo, Eliot H. Ohlstein, Nambi Aiyar, Robert N. Willette,

Cardiovascular Disease and Adiposity

The observation that the novel G-protein-coupled receptor (GPCR) GPR14 and its cognate ligand, urotensin-II (U-II), are expressed within the mammalian vasculature raises the possibility that they may influence cardiohemodynamic homeostasis. To this end, this study examined the vasoactive properties of U-II in rodents, dogs and primates. In vitro, human U-II was a sustained vasoconstrictor with a potency (pD2s < or = 9) approximately an order of magnitude greater than that seen with endothelin-1 (ET-1), making it one of the most, if not the most, potent mammalian vasoconstrictor identified to date. However, in vitro responses exhibited significant anatomical and/or species-dependency, that is, human U-II was a selective 'aorto-coronary' vasoconstrictor in rats and dogs, inactive in mice and contracted all primate arteries studied. In vivo, this peptide evoked a complex, dose-dependent hemodynamic response in the anesthetized primate, culminating in severe myocardial depression and fatal circulatory collapse. As such, U-II may represent a novel neurohumoral regulator of mammalian cardiovascular physiology and pathology in particular disorders characterized by aberrant vascular smooth muscle and/or myocardial function.