title: Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension.
abstract: Clinical studies suggest that aerobic exercise can exert beneficial effects in pulmonary arterial hypertension (PAH), but the underlying mechanisms are largely unknown. We compared the impact of early or late aerobic exercise training on right ventricular function, remodeling and survival in experimental PAH. Male Wistar rats were submitted to normal cage activity (SED), exercise training in early (EarlyEX) and in late stage (LateEX) of PAH induced by monocrotaline (MCT, 60 mg/kg). Both exercise interventions resulted in improved cardiac function despite persistent right pressure-overload, increased exercise tolerance and survival, with greater benefits in EarlyEX+MCT. This was accompanied by improvements in the markers of cardiac remodeling (SERCA2a), neurohumoral activation (lower endothelin-1, brain natriuretic peptide and preserved vascular endothelial growth factor mRNA), metabolism and mitochondrial oxidative stress in both exercise interventions. EarlyEX+MCT provided additional improvements in fibrosis, tumor necrosis factor-alpha/interleukin-10 and brain natriuretic peptide mRNA, and beta/alpha myosin heavy chain protein expression. The present study demonstrates important cardioprotective effects of aerobic exercise in experimental PAH, with greater benefits obtained when exercise training is initiated at an early stage of the disease.
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal. danielmgon@gmail.com.|Centre of Physical Activity, Health and Leasure, Faculty of Sport, University of Porto, Rua Plácido Costa 91, 4200-450, Porto, Portugal. danielmgon@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreira-Gonçalves
authors.affiliation: Department of Chemistry, Organic Chemistry, Natural and Agrofood Products, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.|Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.affiliation: Centre of Physical Activity, Health and Leasure, Faculty of Sport, University of Porto, Rua Plácido Costa 91, 4200-450, Porto, Portugal.
authors.forename: Hélder
authors.initials: H
authors.lastname: Fonseca
authors.affiliation: Department of Chemistry, Organic Chemistry, Natural and Agrofood Products, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.|Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Padrão
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Moreno
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
authors.forename: Ana Filipa
authors.initials: AF
authors.lastname: Silva
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Vasques-Nóvoa
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
authors.forename: Nádia
authors.initials: N
authors.lastname: Gonçalves
authors.affiliation: Centre of Physical Activity, Health and Leasure, Faculty of Sport, University of Porto, Rua Plácido Costa 91, 4200-450, Porto, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Vieira
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
authors.forename: Mário
authors.initials: M
authors.lastname: Santos
authors.affiliation: Department of Chemistry, Organic Chemistry, Natural and Agrofood Products, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.|Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Amado
authors.affiliation: Centre of Physical Activity, Health and Leasure, Faculty of Sport, University of Porto, Rua Plácido Costa 91, 4200-450, Porto, Portugal.
authors.forename: José Alberto
authors.initials: JA
authors.lastname: Duarte
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.|Cardiovascular Research Centre, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.|Department of Cardiothoracic Surgery, Hospital of São João, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal.
authors.forename: Adelino F
authors.initials: AF
authors.lastname: Leite-Moreira
authors.affiliation: Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319, Porto, Portugal. thc@med.up.pt.
authors.forename: Tiago
authors.initials: T
authors.lastname: Henriques-Coelho
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D017079:Exercise Tolerance; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D016686:Monocrotaline; D010805:Physical Conditioning, Animal; D011897:Random Allocation; D017208:Rats, Wistar; D016278:Ventricular Function, Right; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D016686:Monocrotaline
keywords: Aerobic exercise training; Cardioprotection; Monocrotaline; Pulmonary arterial hypertension; Right ventricle