Study Of The Effects Of Fasidotril In SD Rat With Adriamycin-induced Heart Failure

Background and ObjectiveChronic heart failure is a clinical syndrome with high mortality, which is the final stage of many cardiovascular diseases. Both angiotensin-converting enzyme inhibitors andβblockers can greatly improve heart function of patients with heart failure. However, mortality of chronic heart failure is still high, and drugs with function of both angiotensin converting enzyme inhibition and endopeptidase inhibition have potential advantages. Fasidotril is novel medicine can simultaneously inhibit both enzymes. In this study, we investigate the effects of Fasidotril on adriamycin-induced heart failure in SD rats. Materials and Methods40 male Sprague-Dawly rats were randomly divided into three groups(n=8 in Control group ,n=16 in HF group and Fasidotril group).To build up adriamycin-induced chronic heart failure rat models, adriamycin was intraperitoneally injected to HF group and Fasidotril group (2.5mg/kg every three days, total six times and doses 15mg/kg). And then the FAS group was given Fasidotril intragastrically daily, while HF group and Control group were given an equivalent volume of 0.9% saline daily for 4 weeks. After above process, left ventricle function was measured by hemodynamic measurements such as HR、LVEDP and±dp/dtmax. Lung and ventricular weight were measured to calculate their respective ratio. Physiopathology detection of cardiac muscle was done by HE dyeing. Immunohistochemical study was performed to assess the expression of Cox-2 in the paraventricular nucleus. The levels of NE、ANP and AngII in plasma and the cardiac muscular tissue were quantified using ELISA methods. The Cox-2 protein level was measured with Western blot technique in the cardiac muscular tissue.Results(1) The hemodynamic measurements : Compared with Control group, LVEDP and HR were increased in HF group and FAS group(P<0.05.Compared with HF group, LVEDP and HR were significantly reduced in FAS group(P<0.01.HF group and FAS group have lower±dp /dtmax than Control group ,and FAS group have higher±dp /dtmax than HF group. (2) The expression of AngII in plasma and the cardiac muscular tissue. Compared with Control group, AngII was increased in HF group and FAS group(P<0.01). Compared with HF group, AngII was significantly reduced in FAS group(P<0.01).(3) The expression of NE in plasma. HF group and FAS group had higher NE than Control group(P<0.01),but FAS group had lower NE than HF group(P<0.01).(4) The expression of ANP in plasma and the cardiac muscular tissue. Compared with Control group, ANP was reduced in HF group and FAS group (P<0.05). Compared with HF group, ANP were increased in FAS group(P<0.05).Conclusions1. Fasidotril can reduce the plasma concentration of NE and AngII in heart failure induced by adriamycin in the rats. It may suggest that Fasidotril could lesson the activity of renin-angiotensin system and the sympathetic nervous system.2. Fasidotril could reduce the change of hemodynamic parameters in rats. It indicates that Fasidotril may improve heart function.