Luciano Bernardes Leite, Leôncio Lopes Soares, Alexandre Martins Oliveira Portes, Bruna Aparecida Fonseca da Silva, Taís Rodrigues Dias, Thayana Inácia Soares, Mirian Quintão Assis, Luiz Otávio Guimarães-Ervilha, Miguel Araújo Carneiro-Júnior, Pedro Forte, Mariana Machado-Neves, Emily Correna Carlo Reis, Antônio José Natali
{"title":"联合运动对单苦参碱所致肺动脉高压肺动脉及右心有害重构的影响。","authors":"Luciano Bernardes Leite, Leôncio Lopes Soares, Alexandre Martins Oliveira Portes, Bruna Aparecida Fonseca da Silva, Taís Rodrigues Dias, Thayana Inácia Soares, Mirian Quintão Assis, Luiz Otávio Guimarães-Ervilha, Miguel Araújo Carneiro-Júnior, Pedro Forte, Mariana Machado-Neves, Emily Correna Carlo Reis, Antônio José Natali","doi":"10.1152/japplphysiol.00379.2024","DOIUrl":null,"url":null,"abstract":"<p><p>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 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 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 Ca<sup>2+</sup> 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. 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.<b>NEW & NOTEWORTHY</b> This study reveals that combined exercise improves tolerance to physical effort, prevents increases in pulmonary artery resistance, and conserves the right heart function during the progression of pulmonary arterial hypertension. Our analyses show that combined exercise hinders harmful right ventricular and lung structural remodeling and oxidative stress, which reflects in the maintenance of right ventricular myocytes' contractile function by preserving the intracellular calcium cycling. An attenuated progression of the disease impacts positively on its prognosis.</p>","PeriodicalId":15160,"journal":{"name":"Journal of applied physiology","volume":" ","pages":"182-194"},"PeriodicalIF":3.3000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Combined exercise hinders the progression of pulmonary and right heart harmful remodeling in monocrotaline-induced pulmonary arterial hypertension.\",\"authors\":\"Luciano Bernardes Leite, Leôncio Lopes Soares, Alexandre Martins Oliveira Portes, Bruna Aparecida Fonseca da Silva, Taís Rodrigues Dias, Thayana Inácia Soares, Mirian Quintão Assis, Luiz Otávio Guimarães-Ervilha, Miguel Araújo Carneiro-Júnior, Pedro Forte, Mariana Machado-Neves, Emily Correna Carlo Reis, Antônio José Natali\",\"doi\":\"10.1152/japplphysiol.00379.2024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 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 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 Ca<sup>2+</sup> 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. 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.<b>NEW & NOTEWORTHY</b> This study reveals that combined exercise improves tolerance to physical effort, prevents increases in pulmonary artery resistance, and conserves the right heart function during the progression of pulmonary arterial hypertension. Our analyses show that combined exercise hinders harmful right ventricular and lung structural remodeling and oxidative stress, which reflects in the maintenance of right ventricular myocytes' contractile function by preserving the intracellular calcium cycling. An attenuated progression of the disease impacts positively on its prognosis.</p>\",\"PeriodicalId\":15160,\"journal\":{\"name\":\"Journal of applied physiology\",\"volume\":\" \",\"pages\":\"182-194\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of applied physiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1152/japplphysiol.00379.2024\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/29 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of applied physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/japplphysiol.00379.2024","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
Combined exercise hinders the progression of pulmonary and right heart harmful remodeling in monocrotaline-induced pulmonary arterial hypertension.
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 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 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. 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.NEW & NOTEWORTHY This study reveals that combined exercise improves tolerance to physical effort, prevents increases in pulmonary artery resistance, and conserves the right heart function during the progression of pulmonary arterial hypertension. Our analyses show that combined exercise hinders harmful right ventricular and lung structural remodeling and oxidative stress, which reflects in the maintenance of right ventricular myocytes' contractile function by preserving the intracellular calcium cycling. An attenuated progression of the disease impacts positively on its prognosis.
期刊介绍:
The Journal of Applied Physiology publishes the highest quality original research and reviews that examine novel adaptive and integrative physiological mechanisms in humans and animals that advance the field. The journal encourages the submission of manuscripts that examine the acute and adaptive responses of various organs, tissues, cells and/or molecular pathways to environmental, physiological and/or pathophysiological stressors. As an applied physiology journal, topics of interest are not limited to a particular organ system. The journal, therefore, considers a wide array of integrative and translational research topics examining the mechanisms involved in disease processes and mitigation strategies, as well as the promotion of health and well-being throughout the lifespan. Priority is given to manuscripts that provide mechanistic insight deemed to exert an impact on the field.