| Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations. | |
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MedLine Citation:
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PMID: 20958293 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Aortic valve stenosis (AVS) is associated with significant cardiovascular morbidity and mortality. To date, no therapeutic modality has been shown to be effective in retarding AVS progression. We evaluated the effect of angiotensin-converting enzyme inhibition with ramipril on disease progression in a recently developed rabbit model of AVS. EXPERIMENTAL APPROACH: The effects of 8 weeks of treatment with either vitamin D₂ at 25,000 IU for 4 days a week alone or in combination with ramipril (0.5 mg·kg⁻¹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valve:outflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. KEY RESULTS: Treatment with ramipril significantly reduced AV(BS) and improved aortic valve :outflow tract flow velocity ratio. The intravalvular content of the pro-oxidant thioredoxin-interacting protein was decreased significantly with ramipril treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations and vascular responses to ACh, was improved significantly with ramipril treatment. CONCLUSIONS AND IMPLICATIONS: Ramipril retards the development of AVS, reduces valvular thioredoxin-interacting protein accumulation and limits endothelial dysfunction in this animal model. These findings provide important insights into the mechanisms of AVS development and an impetus for future human studies of AVS retardation using an angiotensin-converting enzyme inhibitor. |
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Authors:
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Doan Tm Ngo; Irene Stafford; Aaron L Sverdlov; Weier Qi; Ronald D Wuttke; Yuan Zhang; Darren J Kelly; Helen Weedon; Malcolm D Smith; Jennifer A Kennedy; John D Horowitz |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of pharmacology Volume: 162 ISSN: 1476-5381 ISO Abbreviation: Br. J. Pharmacol. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-01-13 Completed Date: 2011-07-26 Revised Date: 2012-02-01 |
Medline Journal Info:
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Nlm Unique ID: 7502536 Medline TA: Br J Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 722-32 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society. |
Affiliation:
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Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of Adelaide, South Australia, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin-Converting Enzyme Inhibitors
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pharmacology* Animals Aortic Valve / drug effects, physiology Aortic Valve Stenosis / drug therapy*, physiopathology, prevention & control*, ultrasonography Arginine / analogs & derivatives, blood Carrier Proteins / metabolism Disease Models, Animal Disease Progression Echocardiography Enzyme Inhibitors / blood Ergocalciferols / therapeutic use Humans Male Rabbits Ramipril / pharmacology* Vitamins / therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Carrier Proteins; 0/Enzyme Inhibitors; 0/Ergocalciferols; 0/TXNIP protein, human; 0/Vitamins; 30315-93-6/N,N-dimethylarginine; 74-79-3/Arginine; 87333-19-5/Ramipril |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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