| Chronic urotensin II receptor antagonist treatment does not alter hypertrophy or fibrosis in a rat model of pressure-overload hypertrophy. | |
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MedLine Citation:
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PMID: 20452383 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Urotensin II (UII) is a potential mediator in the pathogenesis of cardiovascular disease, and inhibition of its actions at the urotensin receptor (UT) has been shown to improve cardiac function and structural changes of the myocardium in a model of myocardial infarction. In this study we utilized a model of pressure-overload hypertrophy induced by abdominal aortic constriction (AAC) which resulted in hypertrophy, increased fibrosis and impaired diastolic and systolic function. These changes were associated with a 4-fold increase in UII protein expression in the myocardium. Treatment of animals with a selective UT (SB-657510) antagonist for 20 weeks at a dose of 1500 ppm did not improve cardiac function as assessed by echocardiography and pressure-volume loop analysis, nor did it inhibit left ventricular hypertrophy or fibrosis. We hypothesize that other neurohumoral pathways may have a greater involvement in the pathogenesis of this model. Targeting the UII system appears to be insufficient to observe a beneficial outcome. |
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Authors:
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Andrew R Kompa; Bing H Wang; Arintaya Phrommintikul; Pei Y Ho; Darren J Kelly; David J Behm; Stephen A Douglas; Henry Krum |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-07 |
Journal Detail:
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Title: Peptides Volume: 31 ISSN: 1873-5169 ISO Abbreviation: Peptides Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-07-16 Completed Date: 2010-11-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008690 Medline TA: Peptides Country: United States |
Other Details:
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Languages: eng Pagination: 1523-30 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Medicine, Monash University, Alfred Hospital, Victoria, Australia. andrew.kompa@med.monash.edu.au |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Cardiomegaly / metabolism, prevention & control Cardiotonic Agents / blood, pharmacokinetics, pharmacology*, therapeutic use* Cells, Cultured Disease Models, Animal Disease Progression Drug Evaluation, Preclinical Fibroblasts / drug effects Fibrosis / prevention & control Heart / drug effects, physiopathology Heart Failure / mortality, physiopathology, prevention & control* Hypertrophy, Left Ventricular / drug therapy*, metabolism, physiopathology Male Myocardial Infarction / drug therapy, metabolism Myocardium / cytology, metabolism, pathology Random Allocation Rats Rats, Sprague-Dawley Receptors, G-Protein-Coupled / antagonists & inhibitors* Sulfonamides / blood, pharmacokinetics, pharmacology*, therapeutic use* Up-Regulation / drug effects Urotensins / antagonists & inhibitors, metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Receptors, G-Protein-Coupled; 0/SB 657510; 0/Sulfonamides; 0/Urotensins; 0/Uts2r protein, rat; 9047-55-6/urotensin II |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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