Combined exercise hinders the progression of pulmonary and right heart harmful remodeling in monocrotaline-induced pulmonary arterial hypertension.

Abstract

The aim of this study was to test whether combined physical exercise training of moderate intensity executed during the development of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) hinders the progression of pulmonary and right heart harmful functional and structural remodeling in rats. Wistar rats were injected with MCT (60 mg/kg) and after 24 hours were exposed to a combined exercise training program: aerobic exercise (Treadmill running - 60 min/day; 60% of maximum running speed); and resistance exercise (Vertical ladder climbing - 15 climbs; 60% of maximum carrying load), on alternate days, 5 days/week, for approximately 3 weeks. After euthanasia, lung, and right ventricle (RV) were excised and processed for histological, single myocyte and biochemical analyses. Combined exercise increased the tolerance to physical effort (time until fatigue and relative maximum load), and prevented increases in pulmonary artery resistance (TA/TE) and reductions in RV function (TAPSE). Moreover, in myocytes isolated from the RV, combined exercise preserved contraction amplitude, as well as contraction and relaxation velocities, and inhibited reductions in the amplitude and maximum speeds to peak and to decay of the intracellular Ca²⁺ transient. Furthermore, combined exercise avoided RV (RV weight, cardiomyocyte, extracellular matrix, collagen, inflammatory infiltrate, and extracellular matrix) and lung (pulmonary alveoli and alveolar septum) harmful structural remodeling. Additionally, combined exercise restricted RV (NO and CP) and lung (CAT, GST, and NO) oxidative stress. In conclusion, the applied combined exercise regime hinders the progression of pulmonary and right heart functional and structural harmful remodeling in rats with MCT-induced PAH.