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 Ca 2+ current ( I CaL ), and transient outward potassium current ( I to ) were recorded by whole-cell patch-clamp in LV cardiomyocytes. Sarcoplasmic reticulum (SR) Ca 2+ mobilization and Ca 2+ -induced contractile response sensitivity were evaluated in skinned cardiac fibers. Muscarinic type 2 receptor (M 2 R), β 1 -adrenergic receptor (β 1 AR), sarcoplasmic Ca 2+ ATPase (SERCA-2a), type 2 ryanodine receptor (RyR2), L-type Ca 2+ 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 M 2 R mRNA level was decreased. QTc interval at 2nd, 4th, and 8th week as well as APD 30 and APD 90 were increased by DECA. I to density was decreased, while I CaL density was increased by DECA. SR Ca 2+ loading and release were decreased by DECA, while contractile sensitivity to Ca 2+ 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 Ca 2+ mobilization, and increased contractile sensitivity to Ca 2+ .