The blockade of angiotensin AT1 and aldosterone receptors protects rats from synthetic androgen‐induced cardiac autonomic dysfunction

Abstract

This study aimed to evaluate the combined effects of exercise and antagonists of the angiotensin II and aldosterone receptors on cardiac autonomic regulation and ventricular repolarization in rats chronically treated with nandrolone decanoate (ND), a synthetic androgen. Thirty male Wistar rats were divided into six groups: sedentary, trained, ND-treated, trained and ND-treated, trained and treated with both ND and spironolactone, and trained and treated with both ND and losartan. ND (10 mg kg(-1) weekly) and the antagonists (20 mg kg(-1) daily) of the angiotensin II AT1 (losartan) and aldosterone (spironolactone) receptors were administered for 8 weeks. Exercise training was performed using a treadmill five times each week for 8 weeks. Following this 8-week training and treatment period, electrocardiogram recordings were obtained to determine the time and frequency domains of heart rate variability (HRV) and corrected QT interval (QTc). Nandrolone decanoate treatment increased the QTc interval and reduced the parasympathetic indexes of HRV (RMSSD, pNN5 and high-frequency power) in sedentary and trained rats. The ratio between low- and high-frequency power (LF/HF) was higher in ND-treated groups. Both losartan and spironolactone treatments prevented the effects of ND on the QTc interval and the HRV parameters (RMSSD, pNN5, high-frequency power, and the LF/HF ratio). Our results show that chronic treatment with a high dose of ND induces cardiac parasympathetic dysfunction and disturbances in ventricular repolarization in both sedentary and exercised rats. Furthermore, inhibiting the renin-angiotensin-aldosterone system using losartan, or spironolactone, prevented these deleterious effects.