title: 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.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Silvio Rodrigues
authors.initials: SR
authors.lastname: Marques-Neto
authors.forename: Emanuelle Baptista
authors.initials: EB
authors.lastname: Ferraz
authors.forename: Deivid Carvalho
authors.initials: DC
authors.lastname: Rodrigues
authors.forename: Brian
authors.initials: B
authors.lastname: Njaine
authors.forename: Edson
authors.initials: E
authors.lastname: Rondinelli
authors.forename: Antônio Carlos
authors.initials: AC
authors.lastname: Campos de Carvalho
authors.forename: Jose Hamilton Matheus
authors.initials: JH
authors.lastname: Nascimento
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000378:metabolism; D006321:Heart; D054086:KATP Channels / Q000378:metabolism; D019808:Losartan / Q000009:adverse effects; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009277:Nandrolone / Q000009:adverse effects* / Q000031:analogs & derivatives; D000077603:Nandrolone Decanoate; D010805:Physical Conditioning, Animal / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism; D013148:Spironolactone / Q000009:adverse effects; D013256:Steroids / Q000009:adverse effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D054086:KATP Channels; D000451:Mineralocorticoid Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D018161:Receptors, Mineralocorticoid; D013256:Steroids; D013148:Spironolactone; D009277:Nandrolone; D000077603:Nandrolone Decanoate; D019808:Losartan