Ramipril retards development of aortic valve stenosis in a rabbit model: mechanistic considerations

摘要: 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 ramipril on disease progression a recently developed rabbit model AVS. EXPERIMENTAL APPROACH The effects 8 weeks treatment either vitamin D2 at 25 000 IU for 4 days week alone or combination (0.5 mg·kg−1) aortic structure function were examined New Zealand white rabbits. Echocardiographic backscatter (AVBS) valve : outflow tract flow velocity ratio utilized quantify changes function. KEY RESULTS Treatment significantly reduced AVBS improved ratio. The intravalvular content pro-oxidant thioredoxin-interacting protein was decreased treatment. Endothelial function, as measured by asymmetric dimethylarginine concentrations vascular responses ACh, treatment. CONCLUSIONS IMPLICATIONS Ramipril retards development AVS, reduces valvular accumulation limits endothelial dysfunction this animal model. These findings provide important insights into mechanisms an impetus future human studies retardation using inhibitor.