Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice
Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice
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DOI：
10.1038/hr.2011.136
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发表时间：
2012-01-01
影响因子：
5.4
通讯作者：
Sata, Masataka
中科院分区：
文献类型：
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作者：
Higashikuni, Yasutomi;Takaoka, Minoru;Sata, Masataka
阿利吉仑是一种直接的肾素抑制剂，与传统的肾素-血管紧张素系统（RAS）抑制剂相比，其在心肌梗死（MI）后心室重构中的疗效仍有待确定。本研究旨在检测阿利吉仑及其与血管紧张素II受体阻滞剂缬沙坦联合应用对心肌梗死后心室重构的保护作用。通过结扎左前降支动脉在8至12周龄的C57 BL/6小鼠中诱导MI。在MI后3天，将小鼠分为5组，并用以下药物治疗：（1）磷酸盐缓冲盐水（PBS）;（2）肼苯哒嗪（肼苯哒嗪）;（10 mg kg（-1）天（-1））;（3）缬沙坦（8 mg kg（-1）天（-1））;（4）阿利吉仑（25 mg kg（-1）天（-1））;和（5）联合阿利吉仑（25 mg kg（-1）天（-1））和缬沙坦（8 mg kg（-1）天（-1））。对于这些剂量的药物，与PBS组相比，在假手术小鼠中的治疗组之间的降压效果相似。在MI后28天，超声心动图、血流动力学和组织学评估表明，与PBS和肼苯哒嗪组相比，单独使用缬沙坦或阿利吉仑的单药治疗显著且相似地改善了MI后的心室重构。缬沙坦和阿利吉仑的联合治疗更大程度地改善了MI后的心室重构，增强了血管生成，并更大程度地减轻了组织氧化应激和炎症。我们的研究结果表明，阿利吉仑可以替代传统的RAS抑制剂治疗心肌梗死后患者。此外，缬沙坦和阿利吉仑的双重治疗可能比单一治疗更有益。需要进一步的临床试验来充分评估阿利吉仑在心肌梗死后患者中使用的安全性和有效性。高血压研究（2012）35，62-69; doi：10.1038/hr.2011.136;在线发布2011年8月11日
The efficacy of aliskiren, a direct renin inhibitor, in ventricular remodeling after myocardial infarction (MI) compared with conventional renin-angiotensin system (RAS) inhibitors remains to be defined. This study was performed to examine the protective effects of aliskiren and its addition to valsartan, an angiotensin-II receptor blocker, against ventricular remodeling after MI. MI was induced in 8- to 12-week-old C57BL/6 mice by ligating the left anterior descending artery. At 3 days after MI, mice were divided into five groups and were treated with the following: (1) phosphate-buffered saline (PBS); (2) hydralazine (10 mg kg(-1) day(-1)); (3) valsartan (8 mg kg(-1) day(-1)); (4) aliskiren (25 mg kg(-1) day(-1)); and (5) combined aliskiren (25 mg kg(-1) day(-1)) and valsartan (8 mg kg(-1) day(-1)). With these doses of drugs, blood pressure-lowering effects compared with the PBS group were similar among the treated groups in sham-operated mice. At 28 days after MI, echocardiographic, hemodynamic and histological assessments demonstrated that monotherapy with valsartan or aliskiren alone significantly and similarly ameliorated ventricular remodeling after MI compared with the PBS and the hydralazine groups. Combination therapy of valsartan and aliskiren more greatly improved ventricular remodeling after MI with enhancement of angiogenesis and greater attenuation of tissue oxidative stress and inflammation. Our results indicate that aliskiren can be an alternative to conventional RAS inhibitors in the treatment of post-MI patients. Moreover, the dual therapy of valsartan and aliskiren may be more beneficial than either monotherapy. Further clinical trials will be warranted to sufficiently assess the safety and the efficacy of the use of aliskiren in post-MI patients. Hypertension Research (2012) 35, 62-69; doi:10.1038/hr.2011.136; published online 11 August 2011