BACKGROUND The activation of neurohumoral compensatory mechanisms is a common physiological phenomenon in heart failure in order to make up for a failing heart, which will usually have a deteriorating effect on overall health condition. Many medications, such as neprilysin and angiotensin inhibitors, have recently been introduced to remediate neurohumoral changes. This study was conducted to evaluate the efficacy of the sacubitril-aliskiren combination versus the sacubitril-ramipril combination in the treatment of neurohumoral changes in rats with experimentally induced heart failure. METHOD Thirty Wister rats were randomly assigned into five groups each of six rats, the first group was the control group. Intraperitoneal isoprenaline injections of 5 mg/kg/day for 1 week were used to induce experimental models of heart failure in rats of the rest of experimental groups. The second group served as a positive control. Rats in the third, fourth, and fifth groups received oral daily dose of sacubitril 30 mg/kg/day, sacubitril-aliskiren 30,10 mg/kg/day, and sacubitril-ramipril 30/10 mg/kg/day respectively, for 2 weeks. RESULTS Induction of heart failure in rats has significantly increased circulating NT-proBNP (980 ± 116.71 pg/ml), MMP9 (15.85 ± 0.57 ng/ml), troponin-I (3.09 ± 0.147 ng/ml), CK-MB (31.55 ± 1.69 ng/ml), renin (736 ± 45.8 pg/ml), urea (52.1 ± 1.57 mg/dl), and creatinine (0.92 ± 0.04 mg/dl). Significant decreases in glomerular filtration rate (7.031 ± 1.6 ml/hr./kg), urine flow (0.2761 ± 0.06 ml/h/kg), total solute excretion (0.11 ± 0.03 meq/m), and mean blood pressure (83.5 ± 2.6 mm hg) were seen in rats with heart failure. Rats treated with sacubitril combined with aliskiren or ramipril showed a statistically significant reduction of NT-proBNP, MMP9, troponin serum urea, and serum creatinine. Sacubitril-aliskiren or sacubitril-ramipril administration produced a significant increase in renin plasma level, total solute excretion, urine flow, and glomerular filtration rate. CONCLUSION Sacubitril in combination with aliskiren or with ramipril effectively reduced plasma cardiac biomarkers, such as CK-MB, MMP9, and NT-proBNP, in rats with heart failure. Both combinations showed significant remediation of renal function through increasing GFR, urine flow, and total solute excretion, as well as reducing plasma level of renin. Net results revealed that the sacubitril-aliskiren combination has similar remediating effects on neurohumoral changes compared to the sacubitril-ramipril combination.

中文翻译：

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中性溶酶-肾素抑制作用与中性溶酶-血管紧张素抑制作用对心力衰竭大鼠神经体液变化的影响。

背景技术神经体液代偿机制的激活是心力衰竭中常见的生理现象，以弥补心脏衰竭，这通常会对整体健康状况产生恶化的影响。最近已经引入了许多药物，例如中性溶酶和血管紧张素抑制剂，以补救神经体液变化。进行该研究以评估沙比特利-阿利吉仑组合与沙比特利-雷米普利组合在治疗实验性心力衰竭大鼠神经体液变化中的功效。方法将30只Wister大鼠随机分为5组，每组6只，第一组为对照组。腹膜内注射异丙肾上腺素5 mg / kg /天，持续1周，用于在其余实验组的大鼠中诱发心力衰竭的实验模型。第二组作为阳性对照。第三组，第四组和第五组的大鼠分别接受每日口服沙比特利30 mg / kg /天，沙比特利-阿利吉仑30.10 mg / kg /天和沙比特-雷米普利30/10 mg / kg /天的口服剂量2周。结果大鼠心力衰竭的诱导显着增加了循环NT-proBNP（980±116.71 pg / ml），MMP9（15.85±0.57 ng / ml），肌钙蛋白-I（3.09±0.147 ng / ml），CK-MB（31.55） ±1.69 ng / ml），肾素（736±45.8 pg / ml），尿素（52.1±1.57 mg / dl）和肌酐（0.92±0.04 mg / dl）。肾小球滤过率（7.031±1.6 ml / hr。/ kg），尿流（0.2761±0.06 ml / h / kg），总溶质排泄量（0.11±0）显着降低。心力衰竭大鼠的平均血压为（8 meq / m）和（83.5±2.6 mm hg）。用沙比特利联合阿利吉仑或雷米普利治疗的大鼠显示NT-proBNP，MMP9，肌钙蛋白血清尿素和血清肌酐有统计学意义的降低。服用沙比特利-阿利吉仑或沙比特利-雷米普利可使肾素血浆水平，总溶质排泄，尿流和肾小球滤过率显着增加。结论Sacubitril联合阿利吉仑或雷米普利可有效减少心力衰竭大鼠的血浆心脏生物标志物，如CK-MB，MMP9和NT-proBNP。两种组合均显示出通过增加GFR，尿流和总溶质排泄以及降低肾素血浆水平来显着改善肾功能。