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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Angiotensin-converting enzyme inhibitor captopril prevents volume overload cardiomyopathy in experimental chronic aortic valve regurgitation.
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Angiotensin-converting enzyme inhibitor captopril prevents volume overload cardiomyopathy in experimental chronic aortic valve regurgitation.

机译:血管紧张素转换酶抑制剂卡托普利可预防实验性慢性主动脉瓣返流中的容量超负荷心肌病。

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The efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in the treatment of chronic aortic regurgitation (AR) is not well established and remains controversial. The mechanisms by which ACEIs may protect against left-ventricular (LV) volume overload are not well understood, and clinical trials performed until now have yielded conflicting results. This study was therefore performed to assess the effectiveness of two different doses of the ACEI captopril in a rat model of chronic AR. We compared the effects of a 6-month low-dose (LD) (25 mg/kg) or higher dose (HD) (75 mg/kg) treatment with captopril on LV function and hypertrophy in Wistar rats with severe AR. Untreated animals developed LV eccentric hypertrophy and systolic dysfunction. LD treatment did not prevent hypertrophy and provided modest protection against systolic dysfunction. HD treatment preserved LV systolic function and dimensions and tended to slow hypertrophy. The cardiac index remained high and similar among all AR groups, treated or not. Tissue renin–angiotensin system (RAS) analysis revealed that ACE activity was increased in the LVs of AR animals and that only HD treatment significantly decreased angiotensin II receptor mRNA levels. Fibronectin expression was increased in the LV or AR animals, but HD treatment almost completely reversed this increase. The ACE inhibitor captopril was effective at high doses in this model of severe AR. These effects might be related to the modulation of tissue RAS and the control of fibrosis.
机译:血管紧张素转换酶抑制剂(ACEIs)在治疗慢性主动脉瓣关闭不全(AR)中的功效尚不明确,仍存在争议。 ACEIs可以防止左心室(LV)容量超负荷的机制尚未完全了解,并且迄今为止进行的临床试验产生了矛盾的结果。因此,进行该研究以评估两种不同剂量的ACEI卡托普利在慢性AR大鼠模型中的有效性。我们比较了卡托普利6个月低剂量(LD)(25 mg / kg)或更高剂量(HD)(75 mg / kg)用卡托普利治疗对患有严重AR的Wistar大鼠的左室功能和肥大的影响。未经治疗的动物出现左室偏心肥大和收缩功能障碍。 LD治疗不能预防肥大,并提供适度的抗收缩功能障碍保护。 HD治疗保留了LV的收缩功能和大小,并倾向于减慢肥大。不论是否接受治疗,所有AR组的心脏指数均保持较高且相似。组织肾素-血管紧张素系统(RAS)分析显示,AR动物的LV中ACE活性增加,只有HD处理才能显着降低血管紧张素II受体mRNA水平。纤连蛋白表达在LV或AR动物中增加,但是HD治疗几乎完全逆转了这种增加。在这种严重AR模型中,ACE抑制剂卡托普利在高剂量时有效。这些作用可能与组织RAS的调节和纤维化的控制有关。

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