Combined nandrolone and resistance training induced cardiac remodelling and oxidative stress despite enhanced cardiomyocyte contractility.

BACKGROUND: Nandrolone decanoate (ND) is widely used by individuals engaged in resistance training (RT), yet their combined effects on cardiac function remain unclear. OBJECTIVE: To investigate the effects of RT and ND on cardiac structure and function, cellular contractility, Ca² ⁺ -handling protein expression, and redox balance in rats. METHODS: Thirty-two male Wistar rats were assigned to four groups: control (C), trained (C-T), ND (N), and trained ND (N-T). Animals received ND or saline for eight weeks, and RT was performed 3 × /week. Cardiac function was assessed by echocardiography, and isolated cardiomyocytes from the left and right ventricles (LV and RV) were evaluated for contractile function. Protein expression of Ca² ⁺ -handling regulators and oxidative stress markers was quantified. RESULTS: N-T increased LV and RV diameters by 25% and 33%, septal thickness by 41.7%, and reduced ejection fraction by 12.3% compared to N (p < 0.05). LV cardiomyocytes increased width by 29% and volume by 23% in N-T versus C-T (p ≤ 0.04). In LV, N-T showed greater contraction amplitude and velocity at 5 Hz (p = 0.04) and increased relaxation velocity at 1, 3, and 5 Hz (p < 0.01), with shorter time to peak contraction and 50% relaxation at 1 Hz versus N (p = 0.04). In RV, N-T increased contraction amplitude and velocity at 1 and 5 Hz, reduced time to peak at 1 and 3 Hz, shortened relaxation time at 1 Hz, and showed higher relaxation velocity than N and C-T (p < 0.02). Molecular analyses revealed reduced RyR2 expression (25% in LV and 9% in RV) and a 41% decrease in LV phospholamban in N-T versus C-T (p < 0.05). N-T also exhibited higher LV malondialdehyde compared to C-T (p = 0.03). CONCLUSION: ND combined with RT induced adverse cardiac remodeling and impaired ventricular function, despite enhanced cardiomyocyte contractility, and intensified molecular and oxidative disturbances, indicating a maladaptive cardiac response. This is the first study to demonstrate regional differences in contractility and redox balance of isolated ventricular cardiomyocytes under ND plus RT.