Effects of resistance exercise training on the structure and function of cardiac, pulmonary and skeletal muscle tissues in rats with experimental pulmonary arterial hypertension

• Ano de defesa: 2022
• Autor(a) principal: Soares, Leôncio Lopes
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Universidade Federal de Viçosa; Educação Física
• Palavras-chave em Português: Exercícios físicos; Hipertensão pulmonar; Estresse oxidativo; Insuficiência cardíaca; Ratos como animais de laboratório; Educação Física
• Link de acesso: https://locus.ufv.br//handle/123456789/30632; https://doi.org/10.47328/ufvbbt.2022.790

The general objective of this work was to evaluate the effects of low- to moderate- intensity resistance exercise training (RT) on the structure and function of pulmonary, cardiac and skeletal muscle tissues in the stable pulmonary artery hypertension (PAH) model induced by monocrotaline (MCT) in rats. In the first study we focused on evaluating the effects of RT on the structure and oxidative stress of the lung and biceps brachii, as well as on the function, structure, single myocyte contractility and gene and protein expression in the right ventricle (RV). Male Wistar rats were randomly divided into groups: sedentary hypertension until failure; exercise hypertension until failure; sedentary control; exercise control; sedentary hypertension; and exercise hypertension. PAH was induced by two MCT injections (20 mg/kg, with 7 days interval). After the first MCT injection, animals in the exercise groups were submitted to a low- to moderate-intensity RT protocol (Ladder climbing; 55-65% of the maximal carrying load), 5 times/week, during the experimental period. Echocardiographic examination and physical effort tolerance test were carried out at specific time points of the experimental period. After euthanasia, lung, heart, and biceps brachii were dissected, weighed, and processed for histological, single myocyte, and biochemical analysis. The results show that 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). In addition, 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. Moreover, RT retarded 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). Furthermore, RT improved the expression of gene (i.e., miRNA 214) and regulatory proteins of the intracellular Ca 2+ cycling (i.e., PLB ser16 ) as well as of pathological (i.e., α/β-MHC, and Foxo3) and physiological (i.e., Akt, p-Akt, mTOR, p-mTOR, and Bcl-xL) hypertrophy pathways in RV tissue. In conclusion, along with survival and physical effort tolerance enhancement, low- to moderate-intensity RT during the development of stable MCT-induced PAH postpones pulmonary artery resistance increases and prevents RV dysfunction, RV adverse remodeling and myocyte contractility deterioration in rats. In the second study, we investigated whether low- to moderate-intensity RT is beneficial to left ventricle (LV) and LV myocyte contractile functions in such model of stable PAH induced by MCT. Following the experimental design of the first chapter, the results showed that in conjunction with the improvements in survival and physical effort tolerance, RT mitigated the LV and cardiomyocyte contractility dysfunctions promoted by MCT by preserving the ejection fraction and fractional shortening, the amplitude of shortening, and the velocities of contraction and relaxation in cardiomyocytes. Resistance exercise training also prevented increases in LV fibrosis and type I collagen caused by MCT and maintained the type III collagen and myocyte dimensions reduced by MCT. In conclusion, low- to moderate-intensity RT benefits LV and cardiomyocyte contractile functions in rats during the development of stable MCT-induced PAH. Taken together, these results are of clinical relevance insofar as it indicates that low- to moderate-intensity RT may contribute positively to the health and survival of individuals with stable PAH. Keywords: Pulmonary hypertension. Heart failure. Ventricular dysfunction. Physical exercise. Exercise tolerance. Adverse remodeling. Isolated cardiomyocytes.