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 devel- opment 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 h 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/ wk, for 3 wk. After euthanasia, the 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 (acceleration time (TA)/ejection time (TE)] and reductions in RV function [tricuspid annular plane systolic excursion (TAPSE)]. Moreover, in myocytes isolated from the RV, combined exercise pre- served contraction amplitude, as well as contraction and relaxation velocities, and inhibited reductions in the amplitude and max- imum speeds to peak and to decay of the intracellular Ca2 þ transient. Furthermore, combined exercise avoided RV (RV weight, cardiomyocyte, extracellular matrix, collagen, inflammatory infiltrate, and extracellular matrix) and lung (pulmonary alveoli and al- veolar septum) harmful structural remodeling. In addition, combined exercise restricted RV [nitric oxide (NO) and carbonyl protein (CP)] and lung [catalase (CAT), glutathione S-transferase (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.L. B. Leite is thankful to Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brazil (CAPES) for the scholarship. A. J. Natali and M. Machado-Neves are thankful to CNPq—Brazil for the fellowships. This work was supported by the Fundação de Amparo à Pesquisa do Estado de Minas Gerais—Brasil (FAPEMIG)—Grant No. APQ-01485-22, Conselho Nacional de Desenvolvimento Científico e Tecnologico—Brasil (CNPq)—Grant No. 306956/2021-7, and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) – Finance Code 001.info:eu-repo/semantics/publishedVersio