Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations.
Br J Pharmacol
; 162(3): 722-32, 2011 Feb.
Article
em En
| MEDLINE
| ID: mdl-20958293
ABSTRACT
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. EXPERIMENTALAPPROACH:
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⻹) on aortic valve structure and function were examined in New Zealand white rabbits. Echocardiographic aortic valve backscatter (AV(BS)) and aortic valveoutflow tract flow velocity ratio were utilized to quantify changes in valve structure and function. KEYRESULTS:
Treatment with ramipril significantly reduced AV(BS) and improved aortic valveoutflow 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estenose da Valva Aórtica
/
Inibidores da Enzima Conversora de Angiotensina
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Ramipril
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article