Document Detail


Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations.
MedLine Citation:
PMID:  20958293     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  162     ISSN:  1476-5381     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-13     Completed Date:  2011-07-26     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  722-32     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Affiliation:
Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of Adelaide, South Australia, Australia.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin-Converting Enzyme Inhibitors / 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:
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
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