AT^sub 1^ and Aldosterone Receptors Blockade Prevents the Chronic Effect of Nandrolone on the Exercise-Induced Cardioprotection in Perfused rat Heart Subjected to Ischemia and Reperfusion

Myocardial tolerance to ischaemia/reperfusion (I/R) injury is improved by exercise training, but this cardioprotection is impaired by the chronic use of anabolic androgenic steroids (AAS). The present study evaluated whether blockade of angiotensin II receptor (AT^sub 1^-R) with losartan and aldoste...

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Published in:Cardiovascular drugs and therapy 2014-04, Vol.28 (2), p.125
Main Authors: Marques-neto, Silvio Rodrigues, Ferraz, Emanuelle Baptista, Rodrigues, Deivid Carvalho, Njaine, Brian, Rondinelli, Edson, Campos De Carvalho, Antônio Carlos, Nascimento, Jose Hamilton, Matheus
Format: Article
Language:English
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Summary:Myocardial tolerance to ischaemia/reperfusion (I/R) injury is improved by exercise training, but this cardioprotection is impaired by the chronic use of anabolic androgenic steroids (AAS). The present study evaluated whether blockade of angiotensin II receptor (AT^sub 1^-R) with losartan and aldosterone receptor (mineralocorticoid receptor, MR) with spironolactone could prevent the deleterious effect of AAS on the exercise-induced cardioprotection. Male Wistar rats were exercised and treated with either vehicle, nandrolone decanoate (10 mg/kg/week i.m.) or the same dose of nandrolone plus losartan or spironolactone (20 mg/kg/day orally) for 8 weeks. Langendorff-perfused hearts were subjected to I/R and evaluated for the postischaemic recovery of left ventricle (LV) function and infarct size. mRNA and protein expression of angiotensin II type 1 receptor (AT^sub 1^-R), mineralocorticoid receptor (MR), and K^sub ATP^ channels were determined by reverse-transcriptase polymerase chain reaction and Western blotting. Postischaemic recovery of LV function was better and infarct size was smaller in the exercised rat hearts than in the sedentary rat hearts. Nandrolone impaired the exercise-induced cardioprotection, but this effect was prevented by losartan (AT^sub 1^-R antagonist) and spironolactone (MR antagonist) treatments. Myocardial AT^sub 1^-R and MR expression levels were increased, and the expression of the K^sub ATP^ channel subunits SUR2a and Kir6.1 was decreased and Kir6.2 increased in the nandrolone-treated rat hearts. The nandrolone-induced changes of AT^sub 1^-R, MR, and K^sub ATP^ subunits expression was normalized by the losartan and spironolactone treatments. The chronic nandrolone treatment impairs the exercise-induced cardioprotection against ischaemia/reperfusion injury by activating the cardiac renin-angiotensin-aldosterone system and downregulating K^sub ATP^ channel expression.[PUBLICATION ABSTRACT]
ISSN:0920-3206
1573-7241
DOI:10.1007/s10557-013-6503-8