Purpose: Cardiac aldosterone might be involved in the deleterious effects of nandrolone decanoate (ND) on the heart. Therefore, we investigated the involvement of cardiac aldosterone, by the pharmacological block of AT1 or mineralocorticoid receptors, on cardiac hypertrophy and fibrosis.
Methods: Male Wistar rats were randomized into eight groups (n = 14 per group): Control (C), nandrolone decanoate (ND), trained (T), trained ND (TND), ND + losartan (ND + L), trained ND + losartan (TND + L), ND + spironolactone (ND + S), and trained ND + spironolactone (TND + S). ND (10 mg·kg−1·wk−1) was administered during 10 wk of swimming training (five times per week). Losartan (20 mg·kg−1·d−1) and spironolactone (10 mg·kg−1·d−1) were administered in drinking water.
Results: Cardiac hypertrophy was increased 10% by using ND and 17% by ND plus training (P < 0.05). In both groups, there was an increase in the collagen volumetric fraction (CVF) and cardiac collagen type III expression (P < 0.05). The ND treatment increased left ventricle-angiotensin-converting enzyme I activity, AT1 receptor expression, aldosterone synthase (CYP11B2), and 11-β hydroxysteroid dehydrogenase 2 (11β-HSD2) gene expression and inflammatory markers, TGFβ and osteopontin. Both losartan and spironolactone inhibited the increase of CVF and collagen type III. In addition, both treatments inhibited the increase in left ventricle-angiotensin-converting enzyme I activity, CYP11B2, 11β-HSD2, TGFβ, and osteopontin induced by the ND treatment.
Conclusions: We believe this is the first study to show the effects of ND on cardiac aldosterone. Our results suggest that these effects may be associated to TGFβ and osteopontin. Thus, we conclude that the cardiac aldosterone has an important role on the deleterious effects on the heart induced by ND.
1School of Physical Education and Sport, University of São Paulo, São Paulo, SP, BRAZIL; 2Human Movement Laboratory, Sao Judas Tadeu University, São Paulo, SP, BRAZIL; and 3Hypertension Unit, Heart Institute, Medical School, University of São Paulo, São Paulo, SP, BRAZIL
Address for correspondence: Edilamar Menezes de Oliveira, Ph.D., Laboratory of Biochemistry, School of Physical Education and Sport, University of São Paulo, Av. Professor Mello Moraes, 65-Butantã, São Paulo, SP, 05508-900, Brazil; E-mail: firstname.lastname@example.org.
Submitted for publication October 2010.
Accepted for publication February 2011.