Cardiac electrical and contractile disorders promoted by anabolic steroid overdose are associated with late autonomic imbalance and impaired Ca2+ handling

Abstract

Aim: Investigate cardiac electrical and mechanical dysfunctions elicited by chronic anabolic steroid (AS) overdose.

Methods: Male Wistar rats were treated with nandrolone decanoate (DECA) or vehicle (CTL) for 8 weeks. Electrocardiography and heart rate variability were assessed at weeks 2, 4, and 8. Cardiac reactivity to isoproterenol was investigated in isolated rat hearts. Action potential duration (APD) was measured from left ventricular (LV) muscle strips. L-type Ca²⁺ current (I_CaL), and transient outward potassium current (I_to) were recorded by whole-cell patch-clamp in LV cardiomyocytes. Sarcoplasmic reticulum (SR) Ca²⁺ mobilization and Ca²⁺-induced contractile response sensitivity were evaluated in skinned cardiac fibers. Muscarinic type 2 receptor (M₂R), β₁-adrenergic receptor (β₁AR), sarcoplasmic Ca²⁺ ATPase (SERCA-2a), type 2 ryanodine receptor (RyR2), L-type Ca²⁺ channel (CACNA1), Kv4.2 (KCND2), and Kv4.3 (KCND3) mRNA expression levels were measured by quantitative RT-PCR.

Results: Compared with CTL group, DECA group exhibited decreased high frequency band power density (HF) and increased low frequency power density (LF), Cardiac M₂R mRNA level was decreased. QTc interval at 2nd, 4th, and 8th week as well as APD₃₀ and APD₉₀ were increased by DECA. I_to density was decreased, while I_CaL density was increased by DECA. SR Ca²⁺ loading and release were decreased by DECA, while contractile sensitivity to Ca²⁺ was increased versus CTL group.

Conclusion: DECA overdose induced cardiac rhythmic and mechanical abnormalities that can be associated with autonomic imbalance, up-regulated I_CaL and down-regulated I_to, abnormal SR Ca²⁺ mobilization, and increased contractile sensitivity to Ca²⁺.

Keywords: Autonomic balance; Calcium current; Nandrolone; Potassium current; Sarcoplasmic reticulum; Steroids.