Nandrolone alter left ventricular contractility and promotes remodelling involving calcium-handling proteins and renin-angiotensin system in male SHR.

AIMS: 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.

MAIN METHODS: 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, AT1 R, β1 -AR, PLB, p-PLBser16 and SERCA2a was performed.

KEY FINDINGS: Nandrolone increased hypertension in SHR rats and enalapril reduced blood pressure to values below those of the control. NDL increased +dP/dtmax , -dP/dtmax 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, AT1 R and β1-AR proteins were increased in the NDL, and enalapril decreased them, except for TNF-α. The ratio p-PLBser16 /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.

SIGNIFICANCE: 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.