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AT1 and Aldosterone Receptors Blockade Prevents the Chronic Effect of Nandrolone on the Exercise-Induced Cardioprotection in Perfused rat Heart Subjected to Ischemia and Reperfusion

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Abstract

Purpose

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 (AT1-R) with losartan and aldosterone receptor (mineralocorticoid receptor, MR) with spironolactone could prevent the deleterious effect of AAS on the exercise-induced cardioprotection.

Methods and Results

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 (AT1-R), mineralocorticoid receptor (MR), and KATP 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 (AT1-R antagonist) and spironolactone (MR antagonist) treatments. Myocardial AT1-R and MR expression levels were increased, and the expression of the KATP channel subunits SUR2a and Kir6.1 was decreased and Kir6.2 increased in the nandrolone-treated rat hearts. The nandrolone-induced changes of AT1-R, MR, and KATP subunits expression was normalized by the losartan and spironolactone treatments.

Conclusion

The chronic nandrolone treatment impairs the exercise-induced cardioprotection against ischaemia/reperfusion injury by activating the cardiac renin-angiotensin-aldosterone system and downregulating KATP channel expression.

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Source of Fundings

This work was supported by the FAPERJ–Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (grant E-26/110.342/2012). JHMN is a research fellow from CNPq. SRMN received a fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

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Authors and Affiliations

  1. Laboratório de Eletrofisiologia Cardíaca Antonio Paes de Carvalho, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bloco G, 21.941-902, Rio de Janeiro, Brazil

    Silvio Rodrigues Marques-Neto, Emanuelle Baptista Ferraz & Jose Hamilton Matheus Nascimento

  2. Laboratório de Metabolismo Macromolecular Firmino Torres de Castro, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Deivid Carvalho Rodrigues & Edson Rondinelli

  3. Laboratório de Cardiologia Celular e Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil

    Brian Njaine & Antônio Carlos Campos de Carvalho

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  1. Silvio Rodrigues Marques-Neto
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  2. Emanuelle Baptista Ferraz
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Correspondence to Jose Hamilton Matheus Nascimento.

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Marques-Neto, S.R., Ferraz, E.B., Rodrigues, D.C. et al. AT1 and Aldosterone Receptors Blockade Prevents the Chronic Effect of Nandrolone on the Exercise-Induced Cardioprotection in Perfused rat Heart Subjected to Ischemia and Reperfusion. Cardiovasc Drugs Ther 28, 125–135 (2014). https://doi.org/10.1007/s10557-013-6503-8

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