| Autor: |
Douglas SA; Department of Cardiovascular Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406-0939, USA. steve_douglas-1@sbphrd.com, Ashton DJ, Sauermelch CF, Coatney RW, Ohlstein DH, Ruffolo MR, Ohlstein EH, Aiyar NV, Willette RN |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of cardiovascular pharmacology [J Cardiovasc Pharmacol] 2000 Nov; Vol. 36 (5 Suppl 1), pp. S163-6. |
| DOI: |
10.1097/00005344-200036051-00051 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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