Open AccessHuman Urotensin-II is a Potent Vasoactive Peptide
Author(s) -
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
Publication year - 2000
Publication title -
journal of cardiovascular pharmacology
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 0.762
H-Index - 100
eISSN - 1533-4023
pISSN - 0160-2446
DOI - 10.1097/00005344-200036051-00051
Subject(s) - urotensin ii , vasodilation , circulatory system , medicine , in vivo , endothelin receptor , vasoconstriction , endocrinology , homeostasis , biology , in vitro , vasoconstrictor agents , receptor , regulator , vasoactive intestinal peptide , vasoactive , hemodynamics , pharmacology , neuropeptide , biochemistry , microbiology and biotechnology , gene
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.