Anabolic steroids induce cardiac renin-angiotensin system and impair the beneficial effects of aerobic training in rats.
We evaluated the effects of swimming and anabolic steroids (AS) on ventricular function, collagen synthesis, and the local renin-angiotensin system in rats. Male Wistar rats were randomized into control (C), steroid (S; nandrolone decanoate; 5 mg/kg sc, 2x/wk), steroid + losartan (SL; 20 mg.kg(-1).day(-1)), trained (T), trained + steroid (T+S), and trained + steroid + losartan (T+SL; n = 14/group) groups. Swimming was performed 5 times/wk for 10 wk. Serum testosterone increased in S and T+S. Resting heart rate was lower in T and T+S. Percent change in left ventricular (LV) weight-to-body weight ratio increased in S, T, and T+S. LV systolic pressure declined in S and T+S. LV contractility increased in T (P < 0.05). LV relaxation increased in T (P < 0.05). It was significantly lower in T+S compared with C. Collagen volumetric fraction (CVF) and hydroxyproline were higher in S and T+S than in C and T (P < 0.05), and the CVF and LV hypertrophy were prevented by losartan treatment. LV-ANG I-converting enzyme activity increased (28%) in the S group (33%), and type III collagen synthesis increased (56%) in T+S but not in T group. A positive correlation existed between LV-ANG I-converting enzyme activity and collagen type III expression (r(2) = 0.88; P < 0.05, for all groups). The ANG II and angiotensin type 1a receptor expression increased in the S and T+S groups but not in T group. Supraphysiological doses of AS exacerbated the cardiac hypertrophy in exercise-trained rats. Exercise training associated with AS induces maladaptive remodeling and further deterioration in cardiac performance. Exercise training associated with AS causes loss of the beneficial effects in LV function induced by exercising. These results suggest that aerobic exercise plus AS increases cardiac collagen content associated with activation of the local renin-angiotensin system.
Rocha
F L
FL
Laboratory of Biochemistry, School of Physical Education and Sport, Avenida Prof. Mello Moraes 65, Butantã, Cidade Universitária, CEP 05508-9000 São Paulo, Brazil.
Carmo
E C
EC
Roque
F R
FR
Hashimoto
N Y
NY
Rossoni
L V
LV
Frimm
C
C
Anéas
I
I
Negrão
C E
CE
Krieger
J E
JE
Oliveira
E M
EM
D045930:Anabolic Agents / Q000633:toxicity*; D000804:Angiotensin II / Q000378:metabolism; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000633:toxicity; D000077603:Nandrolone Decanoate; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013550:Swimming; D013739:Testosterone / Q000097:blood; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
D045930:Anabolic Agents; D047228:Angiotensin II Type 1 Receptor Blockers; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D013739:Testosterone; D009277:Nandrolone; D003094:Collagen; D007703:Peptidyl-Dipeptidase A; D000077603:Nandrolone Decanoate; D019808:Losartan; D006909:Hydroxyproline