Department of Medicine, Vascular Disease and Therapeutics Research Group, Basil Hetzel Institute, The Queen Elizabeth Hospital, The University of Adelaide, South Australia, Australia.
Br J Pharmacol. 2011 Feb;162(3):722-32. doi: 10.1111/j.1476-5381.2010.01084.x.
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.
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.
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.
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.
主动脉瓣狭窄（AVS）与重大心血管发病率和死亡率相关。迄今为止，尚无治疗方法被证明可有效延缓 AVS 进展。我们评估了血管紧张素转换酶抑制剂雷米普利对最近开发的 AVS 兔模型中疾病进展的影响。
评估了每周 4 天给予 25,000 IU 维生素 D₂ 单独或与雷米普利（0.5 mg·kg⁻¹）联合治疗 8 周对新西兰白兔主动脉瓣结构和功能的影响。超声心动图主动脉瓣背向散射（AV(BS)）和主动脉瓣：流出道流速比用于量化瓣膜结构和功能的变化。
雷米普利治疗显著降低了 AV(BS)并改善了主动脉瓣：流出道流速比。雷米普利治疗可显著降低促氧化还原型硫氧还蛋白相互作用蛋白的腔内含量。雷米普利治疗可显著改善不对称二甲基精氨酸浓度和血管对 ACh 的反应性等内皮功能。
雷米普利可延缓 AVS 的发展，减少瓣膜硫氧还蛋白相互作用蛋白的积累，并限制该动物模型中的内皮功能障碍。这些发现为 AVS 发展的机制提供了重要的见解，并为未来使用血管紧张素转换酶抑制剂延缓 AVS 的人类研究提供了动力。
