Resistance Exercise Training Mitigates Cardiac Remodeling Induced by a High-Fat Diet in Rodents: A Systematic Review. / O Treinamento Resistido Atenua a Remodelação Cardíaca Induzida por uma Dieta Hiperlipídica em Roedores: Uma Revisão Sistemática.

BACKGROUND: Obesity is associated with the development of cardiovascular diseases and is a serious public health problem. In animal models, high-fat diet (HFD) feeding impairs cardiac structure and function and promotes oxidative stress and apoptosis. Resistance exercise training (RT), however, has been recommended as coadjutant in the treatment of cardiometabolic diseases, including obesity, because it increases energy expenditure and stimulates lipolysis. OBJECTIVE: In this systematic review, we aimed to assess the benefits of RT on the heart of rats and mice fed HFD. METHODS: Original studies were identified by searching PubMed, Scopus, and Embase databases from December 2007 to December 2022. This study was conducted in accordance with the criteria established by PRISMA and registered in PROSPERO (CRD42022369217). The risk of bias and methodological quality was evaluated by SYRCLE and CAMARADES, respectively. Eligible studies included original articles published in English that evaluated cardiac outcomes in rodents submitted to over 4 weeks of RT and controlled by a sedentary, HFD-fed control group (n = 5). RESULTS: The results showed that RT mitigates cardiac oxidative stress, inflammation, and endoplasmic reticulum stress. It also modifies the activity of structural remodeling markers, although it does not alter biometric parameters, histomorphometric parameters, or the contractile function of cardiomyocytes. CONCLUSION: Our results indicate that RT partially counteracts the HFD-induced adverse cardiac remodeling by increasing the activity of structural remodeling markers; elevating mitochondrial biogenesis; reducing oxidative stress, inflammatory markers, and endoplasmic reticulum stress; and improving hemodynamic, anthropometric, and metabolic parameters.

FUNDAMENTO: A obesidade está associada ao desenvolvimento de doenças cardiovasculares e constitui um grave problema de saúde pública. Em modelos animais, a alimentação com uma dieta hiperlipídica (DH) compromete a estrutura e a função cardíaca e promove estresse oxidativo e apoptose. O treinamento resistido (TR), entretanto, tem sido recomendado como coadjuvante no tratamento de doenças cardiometabólicas, incluindo a obesidade, porque aumenta o gasto energético e estimula a lipólise. OBJETIVO: Na presente revisão sistemática, nosso objetivo foi avaliar os benefícios do TR no coração de ratos e camundongos alimentados com DH. MÉTODOS: Foram identificados estudos originais por meio de busca nas bases de dados PubMed, Scopus e Embase de dezembro de 2007 a dezembro de 2022. O presente estudo foi conduzido de acordo com os critérios estabelecidos pelo PRISMA e registrado no PROSPERO (CRD42022369217). O risco de viés e a qualidade metodológica foram avaliados pelo SYRCLE e CAMARADES, respectivamente. Os estudos elegíveis incluíram artigos originais publicados em inglês que avaliaram desfechos cardíacos em roedores submetidos a mais de 4 semanas de TR e controlados por um grupo controle sedentário alimentado com DH (n = 5). RESULTADOS: Os resultados mostraram que o TR atenua o estresse oxidativo cardíaco, a inflamação e o estresse do retículo endoplasmático. Também modifica a atividade de marcadores de remodelamento estrutural, apesar de não alterar parâmetros biométricos, parâmetros histomorfométricos ou a função contrátil dos cardiomiócitos. CONCLUSÃO: Nossos resultados indicam que o TR parcialmente neutraliza o remodelamento cardíaco adverso induzido pela DH, aumentando a atividade dos marcadores de remodelamento estrutural; elevando a biogênese mitocondrial; reduzindo o estresse oxidativo, marcadores inflamatórios e estresse do retículo endoplasmático; e melhorando os parâmetros hemodinâmicos, antropométricos e metabólicos.

Combined physical training protects the left ventricle from structural and functional damages in experimental pulmonary arterial hypertension.

BACKGROUND: Under the adverse remodeling of the right ventricle and interventricular septum in pulmonary arterial hypertension (PAH) the left ventricle (LV) dynamics is impaired. Despite the benefits of combined aerobic and resistance physical trainings to individuals with PAH, its impact on the LV is not fully understood. OBJECTIVE: To test whether moderate-intensity combined physical training performed during the development of PAH induced by MCT in rats is beneficial to the LV's structure and function. METHODS: Male Wistar rats were divided into two groups: Sedentary Hypertensive Survival (SHS, n = 7); and Exercise Hypertensive Survival (EHS, n = 7) to test survival. To investigate the effects of combined physical training, another group of rats were divided into three groups: Sedentary Control (SC, n = 7); Sedentary Hypertensive (SH, n = 7); and Exercise Hypertensive (EH, n = 7). PAH was induced through an intraperitoneal injection of MCT (60 mg/kg). Echocardiographic evaluations were conducted on the 22nd day after MCT administration. Animals in the EHS and EH groups participated in a combined physical training program, alternating aerobic (treadmill running: 50 min, 60% maximum running speed) and resistance (ladder climbing: 15 climbs with 1 min interval, 60% maximum carrying load) exercises, one session/day, 5 days/week for approximately 4 weeks. RESULTS: The physical training increased survival and tolerance to aerobic (i.e., maximum running speed) and resistance (i.e., maximum carrying load) exertions and prevented reductions in ejection fraction and fractional shortening. In addition, the physical training mitigated oxidative stress (i.e., CAT, SOD and MDA) and inhibited adverse LV remodeling (i.e., Collagen, extracellular matrix, and cell dimensions). Moreover, the physical training preserved the amplitude and velocity of contraction and hindered the reductions in the amplitude and velocity of the intracellular Ca2+ transient in LV single myocytes. CONCLUSION: Moderate-intensity combined physical training performed during the development of MCT-induced PAH in rats protects their LV from damages to its structure and function and hence increases their tolerance to physical exertion and prolongs their survival.

Effect of Induced Pulmonary Arterial Hypertension on Testicular Parameters of Wistar Rats Subjected to Resistance Exercise Training.

Pulmonary arterial hypertension (PAH) is characterized by elevated arterial pressure and vascular resistance. PAH may cause alterations in the microcirculation of several organs, including the kidney, liver, brain, and testes. However, it remains unclear whether monocrotaline-induced PAH exerts detrimental effects on animal testes. Thus, we analyzed the impact of PAH on testicular morphology and function. Additionally, we investigated the effect of resistance exercise training (RT) on testicular parameters in PAH rats. Eight healthy Wistar rats and eight PAH rats were subjected to RT training for 30 days; the other PAH and healthy rats (n = 8/group) did not exercise. PAH rats had lower reproductive organ weight, serum testosterone levels, testicular glucose, and nitric oxide (NO) levels, Leydig cell parameters, tubular morphometry, germ cell counts, and daily sperm production than healthy animals did. The practice of RT attenuated the negative impact of PAH on the relative weights of the testes and epididymides, Leydig cell number, nuclear volume, testicular NO levels, and seminiferous epithelium architecture. Moreover, RT positively influenced testosterone levels in PAH animals. We conclude that PAH exerts deleterious effects on testicular histology and function. However, RT can be beneficial to the PAH-affected testicular parameters.

Resistance exercise training benefits pulmonary, cardiac, and muscular structure and function in rats with stable pulmonary artery hypertension.

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/ß-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.

Effects of voluntary running on the skeletal muscle of rats with pulmonary artery hypertension.

The effects of voluntary running on the skeletal muscle of rats with pulmonary arterial hypertension (PAH) were tested in the present study. PAH was induced in rats by a single injection of monocrotaline (MCT, 60 mg/kg). Rats in the sedentary hypertension (HS) group had their tolerance to physical exertion reduced throughout the experiment, while those in the sedentary control (SC), exercise control (EC), exercise hypertension (EH) and median exercise (EM) groups maintained or increased. Despite that, the muscular citrate synthase activity was not different between groups. The survival time was higher in the EH (32 days) than in the SH (28 days) (p = 0.0032). SH and EH groups showed a lower percentage of muscle fiber and a higher percentage of extracellular matrix compared to control groups (p < 0.0001). However, the EM and EH groups presented higher percentage of muscle fiber and lower percentage of extracellular matrix than SH group (p < 0.0001). Regarding muscular gene expression, the SH and EM groups showed a lower expression of PGC1-α (p = 0.0024) and a higher expression of VEGF (p = 0.0033) compared to SC, while PGC1-α was elevated in the EH. No difference between groups was found for the carbonylated protein levels (p > 0.05), while the TNF-α/IL-10 ratio was augmented in the EH (p = 0.0277). In conclusion, voluntary running augments the proportion of fiber and affects the gene expression of inflammatory and mitochondrial biogenesis' markers in the skeletal muscle of rats with MCT-induced PAH, which benefits their survival and tolerance to physical effort.

Skeletal muscle dysfunctions in pulmonary arterial hypertension: Effects of aerobic exercise training.

Pulmonary arterial hypertension is associated with skeletal muscle myopathy and atrophy and impaired exercise tolerance. Aerobic exercise training has been recommended as a non-pharmacological therapy for deleterious effects imposed by pulmonary arterial hypertension. Aerobic physical training induces skeletal muscle adaptations via reduced inflammation, improved anabolic processes, decreased hypoxia and regulation of mitochondrial function. These benefits improve physical exertion tolerance and quality of life in patients with pulmonary arterial hypertension. However, the mechanisms underlying the therapeutic potential of aerobic exercise to skeletal muscle disfunctions in patients with pulmonary arterial hypertension are not well understood yet. This minireview highlights the pathways involved in skeletal muscle adaptations to aerobic exercise training in patients with pulmonary arterial hypertension.

O Treinamento Físico Resistido Atenua as Disfunções Ventriculares Esquerdas em Modelo de Hipertensão Arterial Pulmonar / Resistance Exercise Training Mitigates Left Ventricular Dysfunctions in Pulmonary Artery Hypertension Model

Resumo Fundamento A hipertrofia e a dilatação do ventrículo direito observadas na hipertensão arterial pulmonar (HAP) prejudicam a dinâmica do ventrículo esquerdo (VE) achatando o septo interventricular. Objetivo Investigar se o treinamento físico resistido (TFR) de intensidade baixa a moderada é benéfico para funções contráteis do VE e de cardiomiócitos em ratos durante o desenvolvimento de HAP induzida por monocrotalina (MCT). Métodos Foram usados ratos Wistar machos (Peso corporal: ~ 200 g). Para avaliar o tempo até o possível surgimento de insuficiência cardíaca (ou seja, ponto de desfecho), os ratos foram divididos em dois grupos, hipertensão com sedentarismo até a insuficiência (HSI, n=6) e hipertensão com treinamento até a insuficiência (HTI, n=6). Para testar os efeitos do TFR, os ratos foram divididos entre grupos de controle sedentários (CS, n=7), hipertensão com sedentarismo (HS, n=7) e hipertensão com treinamento (HT, n=7). A HAP foi induzida por duas injeções de MCT (20 mg/kg, com um intervalo de 7 dias). Os grupos com treinamento foram submetidos a um protocolo de TFR (subir escadas; 55-65% da máxima carga carregada), 5 dias por semana. A significância estatística foi definida em p <0,05. Resultados O TFR prolongou o ponto de desfecho (~25%), melhorou a tolerância ao esforço físico (~55%) e atenuou as disfunções de contratilidade de VE e de cardiomiócitos promovidas pela MCT preservando a fração de ejeção e o encurtamento fracional, a amplitude do encurtamento, e as velocidades de contração e relaxamento nos cardiomiócitos. O TFR também preveniu os aumentos de fibrose e colágeno tipo I no ventrículo esquerdo causados pela MCT, além de manter as dimensões de miócitos e colágeno tipo III reduzidas por MCT. Conclusão O TFR de intensidade baixa a moderada é benéfico para funções contráteis de VE e cardiomiócitos em ratos durante o desenvolvimento de HAP induzida por MCT.

Abstract Background The right ventricular hypertrophy and dilation observed in pulmonary artery hypertension (PAH) damages the left ventricle (LV) dynamics by flattening the interventricular septum. Objective To investigate whether low- to moderate-intensity resistance exercise training (RT) is beneficial to LV and cardiomyocyte contractile functions in rats during the development of monocrotaline (MCT)-induced PAH. Methods Male Wistar rats (Body weight: ~ 200 g) were used. To assess the time to potential heart failure onset (i.e., end point), rats were divided into sedentary hypertension until failure (SHF, n=6) and exercise hypertension until failure (EHF, n=6) groups. To test RT effects, rats were divided into sedentary control (SC, n = 7), sedentary hypertension (SH, n=7), and exercise hypertension (EH, n=7) groups. PAH was induced by two MCT injections (20 mg/kg, with 7 days interval). Exercise groups were submitted to an RT protocol (Ladder climbing; 55-65% of carrying maximal load), 5 times/week. Statistical significance was assumed at P < 0.05. Results RT prolonged the end point (~25 %), enhanced the physical effort tolerance (~ 55%), and 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. RT also prevented increases in left ventricle fibrosis and type I collagen caused by MCT, and maintained the type III collagen and myocyte dimensions reduced by MCT. Conclusion Low- to moderate-intensity RT benefits LV and cardiomyocyte contractile functions in rats during the development of MCT-induced PAH.

Resistance Exercise Training Mitigates Left Ventricular Dysfunctions in Pulmonary Artery Hypertension Model. / O Treinamento Físico Resistido Atenua as Disfunções Ventriculares Esquerdas em Modelo de Hipertensão Arterial Pulmonar.

BACKGROUND: The right ventricular hypertrophy and dilation observed in pulmonary artery hypertension (PAH) damages the left ventricle (LV) dynamics by flattening the interventricular septum. OBJECTIVE: To investigate whether low- to moderate-intensity resistance exercise training (RT) is beneficial to LV and cardiomyocyte contractile functions in rats during the development of monocrotaline (MCT)-induced PAH. METHODS: Male Wistar rats (Body weight: ~ 200 g) were used. To assess the time to potential heart failure onset (i.e., end point), rats were divided into sedentary hypertension until failure (SHF, n=6) and exercise hypertension until failure (EHF, n=6) groups. To test RT effects, rats were divided into sedentary control (SC, n = 7), sedentary hypertension (SH, n=7), and exercise hypertension (EH, n=7) groups. PAH was induced by two MCT injections (20 mg/kg, with 7 days interval). Exercise groups were submitted to an RT protocol (Ladder climbing; 55-65% of carrying maximal load), 5 times/week. Statistical significance was assumed at P < 0.05. RESULTS: RT prolonged the end point (~25 %), enhanced the physical effort tolerance (~ 55%), and 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. RT also prevented increases in left ventricle fibrosis and type I collagen caused by MCT, and maintained the type III collagen and myocyte dimensions reduced by MCT. CONCLUSION: Low- to moderate-intensity RT benefits LV and cardiomyocyte contractile functions in rats during the development of MCT-induced PAH.

FUNDAMENTO: A hipertrofia e a dilatação do ventrículo direito observadas na hipertensão arterial pulmonar (HAP) prejudicam a dinâmica do ventrículo esquerdo (VE) achatando o septo interventricular. OBJETIVO: Investigar se o treinamento físico resistido (TFR) de intensidade baixa a moderada é benéfico para funções contráteis do VE e de cardiomiócitos em ratos durante o desenvolvimento de HAP induzida por monocrotalina (MCT). MÉTODOS: Foram usados ratos Wistar machos (Peso corporal: ~ 200 g). Para avaliar o tempo até o possível surgimento de insuficiência cardíaca (ou seja, ponto de desfecho), os ratos foram divididos em dois grupos, hipertensão com sedentarismo até a insuficiência (HSI, n=6) e hipertensão com treinamento até a insuficiência (HTI, n=6). Para testar os efeitos do TFR, os ratos foram divididos entre grupos de controle sedentários (CS, n=7), hipertensão com sedentarismo (HS, n=7) e hipertensão com treinamento (HT, n=7). A HAP foi induzida por duas injeções de MCT (20 mg/kg, com um intervalo de 7 dias). Os grupos com treinamento foram submetidos a um protocolo de TFR (subir escadas; 55-65% da máxima carga carregada), 5 dias por semana. A significância estatística foi definida em p <0,05. RESULTADOS: O TFR prolongou o ponto de desfecho (~25%), melhorou a tolerância ao esforço físico (~55%) e atenuou as disfunções de contratilidade de VE e de cardiomiócitos promovidas pela MCT preservando a fração de ejeção e o encurtamento fracional, a amplitude do encurtamento, e as velocidades de contração e relaxamento nos cardiomiócitos. O TFR também preveniu os aumentos de fibrose e colágeno tipo I no ventrículo esquerdo causados pela MCT, além de manter as dimensões de miócitos e colágeno tipo III reduzidas por MCT. CONCLUSÃO: O TFR de intensidade baixa a moderada é benéfico para funções contráteis de VE e cardiomiócitos em ratos durante o desenvolvimento de HAP induzida por MCT.

Is the Wistar Rat a more Suitable Normotensive Control for SHR to Test Blood Pressure and Cardiac Structure and Function?

Abstract Background: There are divergences in the literature regarding the experimental model (Wistar-WIS or Wistar Kyoto-WKY) to be used as a Spontaneously Hypertensive Rat (SHR) control. The characterization of these models in terms of cardiovascular parameters provides researchers with important tools at the time of selection and application in scientific research. Objective: The aim of this study was to evaluate the use of WIS and WKY as a Spontaneously Hypertensive Rat (SHR) control by assessing the long-term behavior of blood pressure and cardiac structure and function in these strains. Methods: To this end, WIS, WKY, and SHR underwent longitudinal experiments. Blood pressure and body mass were measured every two weeks from the 8th to the 72nd. Echocardiographic analysis was performed in all groups with 16, 48, and 72 weeks of life. After having applied the normality test, the Two-Way ANOVA of repeated measures followed by the Tukey post hoc test was used. A significance level of 5% was established. Results: The WIS group showed higher body mass (p<0.05), while the WKY and SHR presented higher body mass variation over time (p<0.05). SHR exhibited increased values of systolic, diastolic, and mean blood pressure when compared to WKY and WIS, whereas the WKY generally showed higher values than WIS (p<0.05). Regarding the cardiac function, SHR showed reduced values, while the WKY presented an early decrease when compared to WIS with aging (p<0.05). Conclusion: WIS is a more suitable normotensive control for SHR than WKY in experiments to test blood pressure and cardiac structure and function.

Effects of aerobic exercise training and açai supplementation on cardiac structure and function in rats submitted to a high-fat diet.

This study evaluated the effect of aerobic exercise training (AET) and supplementation with açai on cardiac structure and function in rats submitted to a high-fat diet. Two-month old Fischer male rats were divided into 5 groups: Control (C), High-fat Diet (H), High-fat Diet + Açai (HA), High-fat Diet + AET (HT), High-fat Diet + Açai + AET (HAT). The high-fat diet had 21.8% lard and 1% cholesterol (H and HT), or supplemented with 1% lyophilized açai pulp (HA and HAT). The HT and HAT groups performed AET on a treadmill (5 days/week, 1 h/day, 60% of the maximum running speed) for 8 weeks. Exercise tolerance test were performed, and adiposity index calculated. After euthanasia, the left ventricle (LV) was dissected and processed for histological, single myocyte intracellular calcium ([Ca2+]i) transient and contractility, oxidative stress and gene expression analysis. AET improved running capacity and reduced the adiposity index. Both AET and açai supplementation inhibited the increase in the LV collagen content, the deleterious effects on the [Ca2+]i transient and contractility in cardiomyocytes and the increment in oxidative stress, caused by the consumption of a high-fat diet. Aerobic exercise training and açai supplementation can mitigate damage caused by high-fat diet in cardiac structure and function, though the combination of treatments had no additional effects.

Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters.

Activation of mineralocorticoid receptor antagonists (MRAs) is cardioprotective; however, this property is lost upon blockade or inactivation of adenosine (ADO) receptor A2b. In this study, we investigated whether the effects of MRAs are mediated by an interaction between cardioprotective ADO receptors A1 and A3. Spironolactone (SPI) or eplerenone (EPL) increased ADO levels in the plasma of treated animals compared to control animals. SPI or EPL increased the protein and activity levels of ecto-5'-nucleotidase (NT5E), an enzyme that synthesizes ADO, compared to control. The levels of ADO deaminase (ADA), which degrades ADO, were not affected by SPI or EPL; however, the activity of ADA was reduced in SPI-treated rats compared to control. Using an isolated cardiomyocyte model, we found inotropic and chronotropic effects, and increased calcium transient [Ca2+]i in cells treated with ADO receptor A1 or A3 antagonists compared to control groups. Upon co-treatment with MRAs, EPL and SPI fully and partially reverted the effects of receptor A1 or A3 antagonism, respectively. Collectively, MRAs in vivo lead to increased ADO bioavailability. In vitro, the rapid effects of SPI and EPL are mediated by an interaction between ADO receptors A1 and A3.

Voluntary running counteracts right ventricular adverse remodeling and myocyte contraction impairment in pulmonary arterial hypertension model.

AIM: Analyze the effects of voluntary running during the development of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) on the right ventricle (RV) structure, RV myocyte contractility and intracellular Ca2+ transient in rats with MCT-induced PAH. MAIN METHODS: Male Wistar rats were housed sedentary or with free access to a running wheel after MCT or saline injection for until HF or median end-point day of HF in sedentary animals (24 days). Echocardiographic examination and exercise tolerance test were carried out at specific time points of the experimental period. After euthanasia, the heart was dissected, weighed and processed for either histological or single myocyte contractility and intracellular Ca2+ transient analyzes. KEY FINDINGS: Voluntary running delayed the onset of HF (29 days) and the increase in pulmonary artery resistance, and improved exercise tolerance. In the median end-point day of HF, exercise retarded RV adverse remodeling (i.e. increase in extracellular matrix and collagen content). At this stage, exercise also delayed impairments in cell contractile function (i.e. amplitude and times to peak and to half relaxation) and intracellular calcium cycling (i.e. amplitude and times to peak and to half decay) in RV single myocytes. SIGNIFICANCE: Along with HF onset delay and physical effort tolerance enhancement, voluntary running during the development of PAH postpones pulmonary artery resistance increases, RV adverse remodeling and myocyte contractility and intracellular calcium cycling deterioration in rats. Therefore, self-paced intermittent exercise of high intensity may contribute positively to the health and survival of individuals with PAH.

Effects of aerobic exercise on the inflammatory cytokine profile and expression of lipolytic and thermogenic genes in ß1-AR-/- mice adipose tissue.

AIM: Investigate the effects of moderate continuous aerobic exercise (MCAE) on the inflammatory cytokine profile and expression of lipolytic and thermogenic genes in ß1-AR-/- mice adipose tissue. MAIN METHODS: Four- to five-month-old male wild type (WT) and ß1-AR-/- mice were divided into groups: WT control (WTc) and trained (WTt); and ß1-AR-/- control (ß1-AR-/-c) and trained (ß1-AR-/-t). Animals from trained groups were submitted to a MCAE regimen (60 min/day; 60% of maximal speed, 5 days/week) on a treadmill, for 8 weeks. After euthanasia, white epididymal (eWAT) and inguinal (iWAT) and brown (BAT) adipose tissues were dissected and used to determine: adiposity index; adipocyte histomorphometry; cytokine concentration; and gene expression. The content of fat, protein and water of the empty carcass was determined. KEY FINDINGS: MCAE reduced body weight, fat mass as well as iWAT and BAT adipocyte area in ß1-AR-/- animals. Aerobic exercise also diminished the concentrations of pro-inflammatory (IL-12p70, TNF-α, IL-6) and anti-inflammatory (IL-10) cytokines in adipose tissue (iWAT, eWAT or BAT) of ß1-AR-/- mice. However, MCAE had no effect on the expression lipolytic and thermogenic genes in ß1-AR-/- mice adipose tissue. SIGNIFICANCE: Alongside reductions in body weight, fat mass and adipocyte area eight weeks of MCAE improves the profile of inflammatory cytokines in ß1-AR-/- mice adipose tissue, despite no change in Lipolytic and thermogenic gene expression.

Physical Exercise and Regulation of Intracellular Calcium in Cardiomyocytes of Hypertensive Rats / Exercício Físico e Regulação de Cálcio Intracelular em Cardiomiócitos de Ratos Hipertensos

Abstract Background: Regulation of intracellular calcium (Ca2+) in cardiomyocytes is altered by hypertension; and aerobic exercise brings benefits to hypertensive individuals. Objective: To verify the effects of aerobic exercise training on contractility and intracellular calcium (Ca2+) transients of cardiomyocytes and on the expression of microRNA 214 (miR-214) in the left ventricle of spontaneously hypertensive rats (SHR). Methods: SHR and normotensive Wistar rats of 16 weeks were divided into 4 groups -sedentary hypertensive (SH); trained hypertensive (TH); sedentary normotensive (SN); and trained normotensive (TN). Animals of the TH and TN groups were subjected to treadmill running program, 5 days/week, 1 hour/day at 60-70% of maximum running velocity for 8 weeks. We adopted a p ≤ 0.05 as significance level for all comparisons. Results: Exercise training reduced systolic arterial pressure in hypertensive rats. In normotensive rats, exercise training reduced the time to 50% cell relaxation and the time to peak contraction and increased the time to 50% decay of the intracellular Ca2+ transients. In SHR, exercise increased the amplitude and reduced the time to 50% decay of Ca2+ transients. Exercise training increased the expression of miR-214 in hypertensive rats only. Conclusion: The aerobic training applied in this study increased the availability of intracellular Ca2+ and accelerated the sequestration of these ions in left ventricular myocytes of hypertensive rats, despite increased expression of miR-214 and maintenance of cell contractility.

Resumo Fundamento: A regulação intracelular de cálcio (Ca2+) em cardiomiócitos é alterada pela hipertensão, e o exercício físico aeróbico traz benefícios para hipertensos. Objetivo: Verificar os efeitos do treinamento físico aeróbico sobre a contratilidade e a concentração intracelular de Ca2+ transitória em miócitos e a expressão do microRNA 214 no ventrículo esquerdo (VE) de ratos espontaneamente hipertensos (SHR). Métodos: SHR e ratos Wistar normotensos com 16 semanas de idade foram divididos em 4 grupos de 13 animais cada: hipertenso sedentário (HS); hipertenso treinado (HT); normotenso sedentário (NS); normotenso treinado (NT). Os animais dos grupos HT e NT foram submetidos a um programa de treinamento progressivo de corrida em esteira, 5 dias/semana, 1 hora/dia, em intensidade de 60-70% da velocidade máxima de corrida, durante 8 semanas. Adotou-se p ≤ 0,05 como nível de significância em todas as comparações. Resultados: O treinamento físico reduziu a pressão arterial sistólica nos animais hipertensos. Nos animais normotensos, o treinamento físico reduziu o tempo para 50% de relaxamento celular e o tempo para o pico de contração celular, mas aumentou o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória. Nos animais SHR, o treinamento físico aumentou a amplitude e reduziu o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória, sem alterar a contratilidade celular. O treinamento físico aumentou a expressão do miR-214 apenas nos animais hipertensos. Conclusão: O treinamento aeróbico utilizado aumenta a disponibilidade e acelera o sequestro de Ca2+ intracelular em miócitos do VE de ratos hipertensos, apesar do aumento da expressão de miR-214 e da manutenção da contratilidade celular.

Physical Exercise and Regulation of Intracellular Calcium in Cardiomyocytes of Hypertensive Rats.

BACKGROUND: Regulation of intracellular calcium (Ca2+) in cardiomyocytes is altered by hypertension; and aerobic exercise brings benefits to hypertensive individuals. OBJECTIVE: To verify the effects of aerobic exercise training on contractility and intracellular calcium (Ca2+) transients of cardiomyocytes and on the expression of microRNA 214 (miR-214) in the left ventricle of spontaneously hypertensive rats (SHR). METHODS: SHR and normotensive Wistar rats of 16 weeks were divided into 4 groups -sedentary hypertensive (SH); trained hypertensive (TH); sedentary normotensive (SN); and trained normotensive (TN). Animals of the TH and TN groups were subjected to treadmill running program, 5 days/week, 1 hour/day at 60-70% of maximum running velocity for 8 weeks. We adopted a p ≤ 0.05 as significance level for all comparisons. RESULTS: Exercise training reduced systolic arterial pressure in hypertensive rats. In normotensive rats, exercise training reduced the time to 50% cell relaxation and the time to peak contraction and increased the time to 50% decay of the intracellular Ca2+ transients. In SHR, exercise increased the amplitude and reduced the time to 50% decay of Ca2+ transients. Exercise training increased the expression of miR-214 in hypertensive rats only. CONCLUSION: The aerobic training applied in this study increased the availability of intracellular Ca2+ and accelerated the sequestration of these ions in left ventricular myocytes of hypertensive rats, despite increased expression of miR-214 and maintenance of cell contractility.