Chronic treatment with anabolic steroids induces ventricular repolarization disturbances: cellular, ionic and molecular mechanism.
The illicit use of supraphysiological doses of androgenic steroids (AAS) has been suggested as a cause of arrhythmia in athletes. The objectives of the present study were to investigate the time-course and the cellular, ionic and molecular processes underlying ventricular repolarization in rats chronically treated with AAS. Male Wistar rats were treated weekly for 8 weeks with 10mg/kg of nandrolone decanoate (DECA n=21) or vehicle (control n=20). ECG was recorded weekly. Action potential (AP) and transient outward potassium current (I(to)) were recorded in rat hearts. Expression of KChIP2, Kv1.4, Kv4.2, and Kv4.3 was assessed by real-time PCR. Hematoxylin/eosin and Picrosirius red staining were used for histological analysis. QTc was greater in the DECA group. After DECA treatment the left, but not right, ventricle showed a longer AP duration than did the control. I(to) current densities were 47.5% lower in the left but not in the right ventricle after DECA. In the right ventricle the I(to) inactivation time-course was slower than in the control group. After DECA the left ventricle showed lower KChIP2 ( approximately 26%), Kv1.4 ( approximately 23%) and 4.3 ( approximately 70%) expression while the Kv 4.2 increased in 4 ( approximately 250%) and diminished in 3 ( approximately 30%) animals of this group. In the right ventricle the expression of I(to) subunits was similar between the treatment and control groups. DECA-treated hearts had 25% fewer nuclei and greater nuclei diameters in both ventricles. Our results strongly suggest that supraphysiological doses of AAS induce morphological remodeling in both ventricles. However, the electrical remodeling was mainly observed in the left ventricle.
Medei
Emiliano
E
Universidade Federal do Rio de Janeiro, Brazil.
Marocolo
Moacir
M
Rodrigues
Deivid de Carvalho
Dde C
Arantes
Paulo Cesar
PC
Takiya
Christina Maeda
CM
Silva
Juliana
J
Rondinelli
Edson
E
Goldenberg
Regina Coeli Dos Santos
RC
de Carvalho
Antonio Carlos Campos
AC
Nascimento
José Hamilton Matheus
JH
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004562:Electrocardiography; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D015640:Ion Channel Gating / Q000187:drug effects*; D051605:Kv Channel-Interacting Proteins / Q000378:metabolism; D008297:Male; D009277:Nandrolone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D009929:Organ Size / Q000187:drug effects; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013256:Steroids / Q000008:administration & dosage* / Q000494:pharmacology*; D016276:Ventricular Function / Q000187:drug effects*
D051605:Kv Channel-Interacting Proteins; D015221:Potassium Channels; D021122:Protein Subunits; D012333:RNA, Messenger; D013256:Steroids; D009277:Nandrolone; D000077603:Nandrolone Decanoate