Administration of anabolic steroid during adolescence induces long-term cardiac hypertrophy and increases susceptibility to ischemia/reperfusion injury in adult Wistar rats.
Chronic administration of anabolic androgenic steroids (AAS) in adult rats results in cardiac hypertrophy and increased susceptibility to myocardial ischemia/reperfusion (IR) injury. Molecular analyses demonstrated that hyperactivation of type 1 angiotensin II (AT1) receptor mediates cardiac hypertrophy induced by AAS and also induces down-regulation of myocardial ATP-sensitive potassium channel (KATP), resulting in loss of exercise-induced cardioprotection. Exposure to AAS during adolescence promoted long-term cardiovascular dysfunctions, such as dysautonomia. We tested the hypothesis that chronic AAS exposure in the pre/pubertal phase increases the susceptibility to myocardial ischemia/reperfusion (IR) injury in adult rats. Male Wistar rats (26day old) were treated with vehicle (Control, n=12) or testosterone propionate (TP) (AAS, 5mgkg-1n=12) 5 times/week during 5 weeks. At the end of AAS exposure, rats underwent 23days of washout period and were submitted to euthanasia. Langendorff-perfused hearts were submitted to IR injury and evaluated for mechanical dysfunctions and infarct size. Molecular analysis was performed by mRNA levels of α-myosin heavy chain (MHC), βMHC and brain-derived natriuretic peptide (BNP), ryanodine receptor (RyR2) and sarcoplasmic reticulum calcium ATPase 2a (SERCA2a) by quantitative RT-PCR (qRT-PCR). The expression of AT1 receptor and KATPchannel subunits (Kir6.1 and SURa) was analyzed by qRT-PCR and Western Blot. NADPH oxidase (Nox)-related reactive oxygen species generation was assessed by spectrofluorimetry. The expression of antioxidant enzymes was measured by qRT-PCR in order to address a potential role of redox unbalance. AAS exposure promoted long-term cardiac hypertrophy characterized by increased expression of βMHC and βMHC/αMHC ratio. Baseline derivative of pressure (dP/dt) was impaired by AAS exposure. Postischemic recovery of mechanical properties was impaired (decreased left ventricle [LV] developed pressure and maximal dP/dt; increased LV end-diastolic pressure and minimal dP/dt) and infarct size was larger in the AAS group. Catalase mRNA expression was significantly decreased in the AAS group. In conclusion, chronic administration of AAS during adolescence promoted long-term pathological cardiac hypertrophy and persistent increase in the susceptibility to myocardial IR injury possible due to disturbances on catalase expression.
Laboratory of Cardiovascular Physiology and Pharmacology, Department of Physiological Sciences, Institute of Biology, Federal Rural University of Rio de Janeiro, 23890-000 Seropedica, RJ, Brazil; Laboratory of Cardiac Electrophysiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902 RJ, Brazil.
Fernando de Azevedo Cruz
FAC
Seara
Laboratory of Cellular and Molecular Cardiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902 RJ, Brazil.
Raiana Andrade Quintanilha
RAQ
Barbosa
Laboratory of Cardiac Electrophysiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902 RJ, Brazil.
Dahienne Ferreira
DF
de Oliveira
Laboratory of Endocrine Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902 RJ, Brazil.
Diorney Luiz Souza
DLS
Gran da Silva
Laboratory of Cellular and Molecular Cardiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902 RJ, Brazil.
Adriana Bastos
AB
Carvalho
Laboratory of Endocrine Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902 RJ, Brazil; NUMPEX-Bio, Pólo de Xerém, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902 RJ, Brazil.
Andrea Claudia
AC
Freitas Ferreira
Laboratory of Cardiac Electrophysiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-902 RJ, Brazil.
José Hamilton
JH
Matheus Nascimento
Laboratory of Cardiovascular Physiology and Pharmacology, Department of Physiological Sciences, Institute of Biology, Federal Rural University of Rio de Janeiro, 23890-000 Seropedica, RJ, Brazil. Electronic address: el.olivares@gmail.com.
Emerson Lopes
EL
Olivares
D000375:Aging; D045930:Anabolic Agents / Q000008:administration & dosage / Q000633:toxicity*; D000728:Androgens / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced* / Q000503:physiopathology; D002374:Catalase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D007273:Injections, Intramuscular; D008297:Male; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D043343:Testosterone Propionate / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors
D045930:Anabolic Agents; D000728:Androgens; C000594638:MYH7 protein, rat; D017382:Reactive Oxygen Species; D002374:Catalase; D018995:Myosin Heavy Chains; D043343:Testosterone Propionate
Anabolic steroids; Catalase; IR injury; Myocardial infarction