RESUMO
AIM: We tested the effects of low- to moderate-intensity resistance exercise training (RT) on the structure and function of pulmonary, right ventricle (RV), and skeletal muscle tissues in rats with stable pulmonary artery hypertension (PAH). MAIN METHODS: After the first monocrotaline (MCT; 20 mg/kg) injection, male rats were submitted to a RT program (Ladder climbing; 55-65 % intensity), 5 times/week. Seven days later rats received the second MCT dose. Physical effort tolerance test and echocardiographic examination were performed. After euthanasia, lung, heart, and biceps brachii were processed for histological, single myocyte, and biochemical analysis. KEY FINDINGS: RT improved survival and physical effort tolerance (i.e., maximum carrying load), mitigated the pulmonary artery resistance increase (i.e., TA/TE), and preserved cardiac function (i.e., fractional shortening, ejection fraction, stroke volume and TAPSE). RT counteracted oxidative stress (i.e., CAT, SOD, GST, MDA and NO) and adverse remodeling in lung (i.e., collapsed alveoli) and in biceps brachii (i.e., atrophy and total collagen) tissues. RT delayed RV adverse remodeling (i.e., hypertrophy, extracellular matrix, collagen types I and III, and fibrosis) and impairments in single RV myocyte contractility (i.e., amplitude and velocity to peak and relaxation). RT improved the expression of gene (i.e., miRNA 214) and intracellular Ca2+ cycling regulatory proteins (i.e., PLBser16); and of pathological (i.e., α/ß-MHC and Foxo3) and physiological (i.e., Akt, p-Akt, mTOR, p-mTOR, and Bcl-xL) hypertrophy pathways markers in RV tissue. SIGNIFICANCE: Low- to moderate-intensity RT benefits the structure and function of pulmonary, RV, and skeletal muscle tissues in rats with stable pulmonary artery hypertension.
RESUMO
ABSTRACT: Pulmonary artery hypertension (PAH) imposes right heart and lung detrimental remodeling which impairs cardiac contractility, physical effort tolerance, and survival. The effects of an early moderate-intensity continuous aerobic exercise training on the right ventricle and lung structure, and on contractility and the calcium (Ca2+) transient in isolated myocytes from rats with severe PAH induced by monocrotaline were analyzed. Rats were divided into control sedentary (CS), control exercise (CE), monocrotaline sedentary (MS), and monocrotaline exercise (ME) groups. Animals from control exercise and ME groups underwent a moderate-intensity aerobic exercise on a treadmill (60 min/d; 60% intensity) for 32 days, after a monocrotaline (60 mg/kg body weight i.p.) or saline injection. The pulmonary artery resistance was higher in MS than in control sedentary (1.36-fold) and was reduced by 39.39% in ME compared with MS. Compared with MS, the ME group presented reduced alveolus (17%) and blood vessel (46%) wall, fibrosis (25.37%) and type I collagen content (55.78%), and increased alveolus (52.96%) and blood vessel (146.97%) lumen. In the right ventricle, the ME group exhibited diminished hypertrophy index (25.53%) and type I collagen content (40.42%) and improved myocyte contraction [ie, reduced times to peak (29.27%) and to 50% relax (13.79%)] and intracellular Ca2+ transient [ie, decreased times to peak (16.06%) and to 50% decay (7.41%)] compared with MS. Thus, early moderate-intensity continuous aerobic exercise prevents detrimental remodeling in the right heart and lung increases in the pulmonary artery resistance and dysfunction in single myocyte contraction and Ca2+ cycling in this model.