Introduction Adriamycin (ADR) is an effective antineoplastic agent whose use has been limited by its cardiotoxic side effects. Angiotensin-converting enzyme 2 (ACE2) has emerged as a novel regulator of cardiac function by converting angiotensin II into angiotensin-(1–7). Studies suggest that ACE2 and Ang-(1–7) may play a critical role in the regulation of cardiac function. This study is to investigate the effect of AT1 receptor blocker valsartan on the expression of ACE2 and Ang (1–7) in a rat model of adriamycin-induced dilated cardiomyopathy.
Methods Weight-matched Adult male Wistar rats were randomly divided into three groups as follows: 1. the ADR group, in which 2.5 mg/kg of ADR was weekly injected via a tail vein for 10 weeks (n=25); 2) concomitant AT1 receptor blocker valsartan and ADR, in which valsartan was administered by daily gavage at a dose of 30 mg?kg-1?day-1(n=10); 3. the control group (n=10). Haemodynamics and echocardiographic measurements were obtained at 12 weeks after treatment. The plasma concentrations of Ang II and angiotensin (1–7) were determined by immunoradiometric assay. The expression of ACE2 in left ventricular myocardium was investigated by Immunohistochemistry. The expression of collagen in LV were investigated with Van Gieson staining techniques.
Results LV cavity dilatation was significantly attenuated in ADR-induced dilated cardiomyopathy rats given valsartan. Valsartan partially normalised LV contractile function, which was significantly reduced in ADR rat. The plasma concentrations of Ang II were higher in the ADR group than the control group (p<0.01), which was further increased by valsartan (p<0.01). The plasma concentrations of ang (1-7) was higher in the ADR group than the control group, valsartan treatment further increased the plasma concentrations of ang (1-7) by 1.5-fold (p<0.01). The expression of ACE2 was increased in the ADR group, and was further significantly augmented in valsartan treated rats. Myocardial fibrosis occurred significantly in ADR group, which was partly reversed by valsartan treatment (p<0.01).
Conclusion Pretreatment with the AT1 receptor blocker valsartan can attenuate left ventricular remodelling and failure in a rat model of adriamycin-induced dilated cardiomyopathy by upregulating the expression of angiotensin-converting enzyme 2 and angiotensin-(1–7).
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