Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Espírito Santo, Brazil.
Department of Pharmacy, University of Vila Velha, Espírito Santo, Brazil.
Life Sci. 2018 Sep 1;208:239-245. doi: 10.1016/j.lfs.2018.07.041. Epub 2018 Jul 21.
Hypertension is a highly prevalent disease that has been correlated to severe organ damage and mortality. However, the role of androgens in hypertension is controversial. The aim of this study was to evaluate the cardiac effects of the nandrolone decanoate (NDL) in male SHR.
At 12 weeks of age, male SHR rats were separated into three groups: Control (CON), Nandrolone 10 mg/kg twice weekly (NDL), and NDL plus Enalapril 10 mg/kg/day (NDL-E) groups. The animals were treated for 4 weeks. Haemodynamic parameters were acquired through ventricular catheter implantation. The left ventricle was stained with haematoxylin/eosin or picrosirius red. Western blot analysis of TNF-α, ACE, ATR, β-AR, PLB, p-PLB and SERCA2a was performed.
Nandrolone increased hypertension in SHR rats and enalapril reduced blood pressure to values below those of the control. NDL increased +dP/dt, -dP/dt and cardiac hypertrophy, which were prevented in the NDL-E group. Cardiac collagen deposition was increased in the NDL group, with this effect being attenuated by enalapril in NDL-E animals. TNF-α, ACE, ATR and β1-AR proteins were increased in the NDL, and enalapril decreased them, except for TNF-α. The ratio p-PLB/PLB revealed an increase after nandrolone, which was prevented in the NDL-E group. The SERCA2a expression protein and SERCA2a/PLB were increased in NDL animals, which did not occur in the NDL-E group.
Nandrolone has distinct effects on cardiac function and remodelling in male SHR, altering the hypertension development process in the heart through modulation of calcium handling proteins and the renin-angiotensin system.
高血压是一种高发疾病,与严重的器官损伤和死亡率有关。然而,雄激素在高血压中的作用存在争议。本研究旨在评估癸酸诺龙(NDL)对雄性 SHR 的心脏影响。
12 周龄雄性 SHR 大鼠分为三组:对照组(CON)、每周两次 10mg/kg 癸酸诺龙(NDL)组和 NDL 加依那普利 10mg/kg/天(NDL-E)组。动物治疗 4 周。通过心室导管植入获取血流动力学参数。左心室用苏木精/伊红或苦味酸天狼猩红染色。进行 TNF-α、ACE、ATR、β-AR、PLB、p-PLB 和 SERCA2a 的 Western blot 分析。
NDL 增加了 SHR 大鼠的高血压,依那普利将血压降低至低于对照组的水平。NDL 增加了+dP/dt、-dP/dt 和心脏肥大,NDL-E 组可预防这些作用。NDL 组心脏胶原沉积增加,NDL-E 动物中的依那普利可减轻这种作用。NDL 组 TNF-α、ACE、ATR 和β1-AR 蛋白增加,依那普利降低了这些蛋白,除 TNF-α 外。p-PLB/PLB 比值在 Nandrolone 后增加,NDL-E 组可预防。NDL 组的 SERCA2a 表达蛋白和 SERCA2a/PLB 增加,但 NDL-E 组没有。
NDL 对雄性 SHR 的心脏功能和重塑有明显影响,通过调节钙处理蛋白和肾素-血管紧张素系统改变心脏高血压发展过程。