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Type: Journal article
Title: Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations
Author: Ngo, D.
Stafford, I.
Sverdlov, A.
Qi, W.
Wuttke, R.
Zhang, Y.
Kelly, D.
Weedon, H.
Smith, M.
Kennedy, J.
Horowitz, J.
Citation: British Journal of Pharmacology, 2011; 162(3):722-732
Publisher: Nature Publishing Group
Issue Date: 2011
ISSN: 0007-1188
Statement of
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 and John D Horowitz
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. 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 (AVBS) 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 AVBS 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.
Keywords: aortic valve stenosis; endothelial function; redox stress; ACE inhibitor; thioredoxin-interacting protein; asymmetric dimethylarginine; echocardiography
Rights: © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society
RMID: 0020102413
DOI: 10.1111/j.1476-5381.2010.01084.x
Appears in Collections:Medicine publications

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