| Differential effect of urotensin II on vascular tone in normal subjects and patients with chronic heart failure. | |
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MedLine Citation:
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PMID: 15007012 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Urotensin II (U-II) is a novel vasoactive peptide that also has direct hypertrophic and profibrotic effects on the myocardium. Upregulation of U-II and its receptor has been observed within the heart of patients with chronic heart failure (CHF). Furthermore, plasma levels of U-II have been found to be elevated in some but not all studies in such patients. However, the functional consequences of activation of the U-II system in patients with CHF, assessed by direct administration of exogenous U-II, have not been previously determined. METHODS AND RESULTS: We compared the effect of iontophoresed U-II on skin microvascular tone in normal subjects and patients with CHF, assessed with the use of laser Doppler velocimetry. U-II mediated a dose-dependent vasodilator response in normal subjects (baseline, 137.9+/-52; U-II, 10(-12) mol/L, 145+/-134; U-II, 10(-9) mol/L, 712+/-179; U-II, 10(-7) mol/L, 943+/-139 arbitrary flux units [AFUs], P<0.0001). In contrast, a dose-dependent vasoconstrictor response was observed in patients with CHF (baseline, 336.1+/-129; U-II, 10(-12) mol/L, 317+/-131; U-II, 10(-9) mol/L, 129+/-137; U-II, 10(-7) mol/L, 22.4+/-130 AFUs, P<0.05). Differences in flow between normal subjects and patients with CHF were significant overall (P<0.001, 2-way ANOVA) and at the U-II 10(-9) mol/L and U-II 10(-7) mol/L dose level by Student's unpaired t test (P<0.05, P<0.0001, respectively). In contrast, there was no significant difference between baseline blood flux and any dose of U-II in either group (or between groups) when the opposite polarity was applied. CONCLUSIONS: In addition to direct effects on the myocardium, U-II may contribute to the increased peripheral vascular tone that is characteristic of human CHF. The present observations support the contention that the U-II system may be a potentially important target for pharmacological blockade in the treatment of this condition. |
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Authors:
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Melissa Lim; Suzy Honisett; Christopher D Sparkes; Paul Komesaroff; Andrew Kompa; Henry Krum |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2004-03-08 |
Journal Detail:
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Title: Circulation Volume: 109 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-03-16 Completed Date: 2004-06-28 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1212-4 Citation Subset: AIM; IM |
Affiliation:
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National Health and Medical Research Council of Australia Centre of Clinical Research Excellence in Therapeutics, Monash University, Alfred Hospital, Melbourne, Victoria, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcholine
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pharmacology Disease Progression Dose-Response Relationship, Drug Endothelium, Vascular / drug effects Female Heart Failure / physiopathology* Humans Iontophoresis Laser-Doppler Flowmetry Male Microcirculation / drug effects Middle Aged Muscle, Smooth, Vascular / drug effects* Nitroprusside / pharmacology Receptors, G-Protein-Coupled / drug effects, physiology Skin / blood supply Urotensins / administration & dosage, pharmacology* Vasodilator Agents / administration & dosage, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Receptors, G-Protein-Coupled; 0/UTS2R protein, human; 0/Urotensins; 0/Vasodilator Agents; 15078-28-1/Nitroprusside; 51-84-3/Acetylcholine; 9047-55-6/urotensin II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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