title: Effects of exercise training on circulating and skeletal muscle renin-angiotensin system in chronic heart failure rats.
abstract: BACKGROUND
  Accumulated evidence shows that the ACE-AngII-AT1 axis of the renin-angiotensin system (RAS) is markedly activated in chronic heart failure (CHF). Recent studies provide information that Angiotensin (Ang)-(1-7), a metabolite of AngII, counteracts the effects of AngII. However, this balance between AngII and Ang-(1-7) is still little understood in CHF. We investigated the effects of exercise training on circulating and skeletal muscle RAS in the ischemic model of CHF.
  
  
  RESULTS
  Male Wistar rats underwent left coronary artery ligation or a Sham operation. They were divided into four groups: 1) Sedentary Sham (Sham-S), 2) exercise-trained Sham (Sham-Ex), sedentary CHF (CHF-S), and exercise-trained CHF (CHF-Ex). Angiotensin concentrations and ACE and ACE2 activity in the circulation and skeletal muscle (soleus and plantaris) were quantified. Skeletal muscle ACE and ACE2 protein expression, and AT1, AT2, and Mas receptor gene expression were also evaluated. CHF reduced ACE2 serum activity. Exercise training restored ACE2 and reduced ACE activity in CHF. Exercise training reduced plasma AngII concentration in both Sham and CHF rats and increased the Ang-(1-7)/AngII ratio in CHF rats. CHF and exercise training did not change skeletal muscle ACE and ACE2 activity and protein expression. CHF increased AngII levels in both soleus and plantaris muscle, and exercise training normalized them. Exercise training increased Ang-(1-7) in the plantaris muscle of CHF rats. The AT1 receptor was only increased in the soleus muscle of CHF rats, and exercise training normalized it. Exercise training increased the expression of the Mas receptor in the soleus muscle of both exercise-trained groups, and normalized it in plantaris muscle.
  
  
  CONCLUSIONS
  Exercise training causes a shift in RAS towards the Ang-(1-7)-Mas axis in skeletal muscle, which can be influenced by skeletal muscle metabolic characteristics. The changes in RAS circulation do not necessarily reflect the changes occurring in the RAS of skeletal muscle.
authors.affiliation: Heart Institute (InCor-HCFMUSP), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Igor Lucas
authors.initials: IL
authors.lastname: Gomes-Santos
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Tiago
authors.initials: T
authors.lastname: Fernandes
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Gisele Kruger
authors.initials: GK
authors.lastname: Couto
authors.affiliation: Heart Institute (InCor-HCFMUSP), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Julio César Ayres
authors.initials: JC
authors.lastname: Ferreira-Filho
authors.affiliation: Heart Institute (InCor-HCFMUSP), University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Vera Maria Cury
authors.initials: VM
authors.lastname: Salemi
authors.affiliation: Division of Nephrology, Kidney and Hypertension Hospital, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Fernanda Barrinha
authors.initials: FB
authors.lastname: Fernandes
authors.affiliation: Division of Nephrology, Kidney and Hypertension Hospital, Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Dulce Elena
authors.initials: DE
authors.lastname: Casarini
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Patricia Chakur
authors.initials: PC
authors.lastname: Brum
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Luciana Venturini
authors.initials: LV
authors.lastname: Rossoni
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Edilamar Menezes
authors.initials: EM
authors.lastname: de Oliveira
authors.affiliation: Heart Institute (InCor-HCFMUSP), University of São Paulo Medical School, São Paulo, Brazil; School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Carlos Eduardo
authors.initials: CE
authors.lastname: Negrao
mesh_terms: D000804:Angiotensin II / Q000097:blood / Q000378:metabolism; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D006333:Heart Failure / Q000097:blood* / Q000378:metabolism* / Q000503:physiopathology; D006334:Heart Function Tests; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System
chemical_list: D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2