Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure
Angiotensin II receptor blocker irbesartan attenuates cardiac dysfunction induced by myocardial infarction in the presence of renal failure
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DOI：
10.1038/hr.2015.141
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发表时间：
2016-04
影响因子：
5.4
通讯作者：
R. Watanabe;J. Suzuki;Kouji Wakayama;H. Kumagai;Yuichi Ikeda;H. Akazawa;I. Komuro;M. Isobe
中科院分区：
文献类型：
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作者：
R. Watanabe;J. Suzuki;Kouji Wakayama;H. Kumagai;Yuichi Ikeda;H. Akazawa;I. Komuro;M. Isobe
已知肾素-血管紧张素系统的活性是心力衰竭和肾衰竭的病理生理学中的关键因素。厄贝沙坦是一种血管紧张素II受体阻滞剂，具有非血流动力学的心血管和肾脏保护作用。然而，厄贝沙坦对心力衰竭并发肾功能衰竭的影响尚未阐明。因此，本研究的目的是在大鼠模型中评价厄贝沙坦对心肾综合征病理生理学的影响。采用两步手术方法对大鼠进行肾大部切除术（NTX）。NTX后28天，通过结扎冠状动脉左前降支诱导心肌梗死（MI）。NTX后，动物经口给予溶剂或厄贝沙坦（10 mg/kg-1天-1）。MI后28天收获心脏。心肌梗死与NTX模型大鼠表现出受损的心肌梗死后的生存率和增强心肌炎症相比，MI没有NTX大鼠。厄贝沙坦治疗虽然不能提高NTX心肌梗死大鼠的存活率，但能抑制NTX心肌梗死大鼠的心肌炎症、左室功能下降、心肌纤维化、心肌细胞肥大和肾纤维化。此外，在未接受NTX治疗的MI大鼠心脏中观察到的与氧化应激和炎症相关的蛋白质表达水平（NADPH氧化酶4、磷酸化核因子-κB和磷酸化c-Jun）的增加可通过厄贝沙坦治疗减弱。厄贝沙坦治疗的这些作用与血压无关。我们的结论是，厄贝沙坦心肌梗死后，肾功能不全时，存在心脏保护作用。
The activity of the renin–angiotensin system is known to be a key factor in the pathophysiology of heart failure and renal failure. Irbesartan, an angiotensin II receptor blocker, has non-hemodynamic cardiovascular and renal protective effects. However, the effect of irbesartan on heart failure complicated by renal failure has not yet been elucidated. Thus the purpose of this study was to evaluate the effect of irbesartan on the pathophysiology of cardiorenal syndrome in a rat model. Subtotal nephrectomy (NTX) was performed in rats was using a two-step surgical procedure. Twenty-eight days after NTX, myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery. The animals were orally administered vehicle or irbesartan (10 mg kg− 1 day− 1) after NTX. The hearts were harvested 28 days after MI. MI with NTX model rats showed an impaired post-MI survival rate and enhanced cardiac inflammation in comparison to MI without NTX rats. Although irbesartan treatment did not improve the survival rate, it suppressed cardiac inflammation, left ventricular function decline, cardiac fibrosis, hypertrophy of cardiomyocytes and renal fibrosis in MI with NTX rats. Moreover, increases in protein expression levels related to oxidative stress and inflammation (NADPH oxidase 4, phospho-nuclear factor-κB and phospho-c-Jun) observed in the hearts of non-treated MI with NTX rats were attenuated by irbesartan treatment. These effects of irbesartan treatment were independent of blood pressure. We conclude that irbesartan has a cardioprotective effect after MI when renal dysfunction is present.