Zendaoui Adnane, Lachance Dominic, Roussel Elise, Couet Jacques, Arsenault Marie
Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l'Institut universitaire de Cardiologie et pneumologie de Québec, Université Laval, Québec, Canada.
J Heart Valve Dis. 2012 Jul;21(4):478-86.
Aortic regurgitation (AR) is a disease for which there is currently no effective medical treatment. It has been shown previously in an experimental model of AR that the renin-angiotensin-aldosterone system (RAAS) plays a major role, and that medications blocking the RAAS are effective to protect against left ventricular (LV) hypertrophy and also help to maintain a normal systolic function. The role of aldosterone receptor blockers in this disease has never been evaluated. Thus, the effects were studied of the aldosterone receptor blocking agent spironolactone in a model of chronic AR in rats.
The effects of a six-month treatment with spironolactone were evaluated in adult Wistar rats with severe AR, compared to sham-operated and untreated AR animals.
Spironolactone treatment decreased the total heart weight. In addition, the LV expression of atrial natriuretic peptide mRNA was decreased by spironolactone treatment, as was the expression of collagen 1 and LOX1 mRNAs. Left ventricular fibrosis was decreased by spironolactone treatment.
Spironolactone protected against volume-overload cardiomyopathy in this model of aortic valve regurgitation. The predominant protective effect was a decrease in myocardial fibrosis.
主动脉瓣反流（AR）是一种目前尚无有效药物治疗的疾病。先前在AR实验模型中已表明，肾素-血管紧张素-醛固酮系统（RAAS）起主要作用，且阻断RAAS的药物可有效预防左心室（LV）肥厚，并有助于维持正常的收缩功能。醛固酮受体阻滞剂在该疾病中的作用从未得到评估。因此，研究了醛固酮受体阻断剂螺内酯在大鼠慢性AR模型中的作用。
将螺内酯治疗6个月的效果在患有严重AR的成年Wistar大鼠中进行评估，并与假手术和未治疗的AR动物进行比较。
螺内酯治疗降低了心脏总重量。此外，螺内酯治疗降低了心房利钠肽mRNA在LV中的表达，以及胶原蛋白1和LOX1 mRNA的表达。螺内酯治疗减轻了左心室纤维化。
在该主动脉瓣反流模型中，螺内酯可预防容量超负荷心肌病。主要的保护作用是心肌纤维化的减轻。
