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Updated: Jul 15, 2025

Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Resistance exercise training benefits pulmonary, cardiac, and muscular structure and function in rats with stable
Leôncio Lopes Soares1, Luciano Bernardes Leite1, Luiz Otávio Guimarães Ervilha2
1Universidade Federal de Viçosa, Departamento de Educação Física, Viçosa, Brazil.
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/β-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.
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