Effects of moderate-continuous and high-intensity interval aerobic training on cardiac function of spontaneously hypertensive rats.

The aim of this study was to verify the effects of moderate-intensity continuous (MICT) and high-intensity interval (HIIT) aerobic training on cardiac morphology and function and the mechanical properties of single cardiomyocytes in spontaneously hypertensive rats (SHR) in the compensated phase of hypertension. Sixteen-week-old male SHR and normotensive Wistar (WIS) rats were allocated to six groups of six animals each: SHR CONT or WIS CONT (control); SHR MICT or WIS MICT (underwent MICT, 30 min/day, five days per week for eight weeks); and SHR HIIT or WIS HIIT (underwent HIIT, 30 min/day, five days per week for eight weeks). Total exercise time until fatigue and maximum running speed were determined using a maximal running test before and after the experimental period. Systolic (SAP), diastolic (DAP), and mean (MAP) blood pressures were measured using tail plethysmography before and after the experimental period. Echocardiographic evaluations were performed at the end of the experimental period. The rats were euthanized after in vivo assessments, and left ventricular myocytes were isolated to evaluate global intracellular Ca2+ transient ([Ca2+]i) and contractile function. Cellular measurements were performed at basal temperature (~37°C) at 3, 5, and 7 Hz. The results showed that both training programs increased total exercise time until fatigue and, consequently, maximum running speed. In hypertensive rats, MICT decreased SAP, DAP, MAP, interventricular septal thickness during systole and diastole, and the contraction amplitude at 5 Hz. HIIT increased heart weight and left ventricular wall thickness during systole and diastole and reduced SAP, MAP, and the time to peak [Ca2+]i at all pacing frequencies. In conclusion, both aerobic training protocols promoted beneficial adaptations to cardiac morphology, function, and mechanical properties of single cardiomyocytes in SHR.

Protective effects of whey protein concentrate admixtured of curcumin on metabolic control, inflammation and oxidative stress in Wistar rats submitted to exhaustive exercise.

This work aimed to evaluate the effects of whey protein concentrate (WPC) admixtured of curcumin on metabolic control, inflammation and oxidative stress in Wistar rats submitted to exhaustive exercise. A total of forty-eight male rats were divided into six experimental groups (n 8): standard diet group (AIN-93M), standard diet submitted to exhaustion test group (AIN-93M ET), WPC admixtured of curcumin group (WPC + CCM), WPC + CCM submitted to exhaustion test group (WPC + CCM ET), CCM group and CCM subjected to exhaustion test group (CCM ET). The swimming exhaustion test was performed after 4 weeks of experiment. The consumption of WPC + CCM as well as isolated CCM did not alter the biometric measurements, the animals' food consumption and the hepatic and kidney function, as well as the protein balance of the animals (P > 0·05), but reduced the glycaemia and the gene expression of TNF-α and IL-6 and increased the expression of IL-10 (P < 0·05). The animals that were submitted to the exhaustion test (AIN-93M ET) showed higher aspartate aminotransferase values when compared to the animals that did not perform the exercise (AIN-93 M) (P < 0·05). WPC + CCM reduced the concentration of nitric oxide, carbonylated protein and increased the concentration of catalase (P < 0·05). Both (WPC + CCM and CCM) were able to increase the concentrations of superoxide dismutase (P < 0·05). We concluded that the WPC admixtured of CCM represents a strategy capable of decreasing blood glucose and oxidative and inflammatory damage caused by exhaustive physical exercise in swimming.

Core temperature circadian rhythm across aging in Spontaneously Hypertensive Rats.

The purpose of this study was to evaluate the circadian rhythm of core temperature (Tcore) across aging in Spontaneously Hypertensive Rats (SHR) with comparison to the two rat strains often used as their normotensive control animals, namely, Wistar (WIS) and Wistar Kyoto (WKY). METHODS: WIS, WKY and SHR rats were subdivided into three different groups according their age: WIS16, WIS48, WIS72, WKY16, WKY48, WKY72, SHR16, SHR48 and SHR72 weeks-old. Body mass and blood pressure were periodically measured along the experiments. All animal group had their circadian rhythm of Tcore evaluated over three consecutive days (72 h) by telemetry using an implanted temperature sensor. The Tcore circadian rhythm was averaged in 1-h blocks and analyzed using the cosinor method. RESULTS: Sixteen-week-old SHR (SHR16) presented higher Tcore than WIS16 (from 06am to 06pm) and WKY16 (from 07am to 06pm). Both normotensive groups exhibited increases in Tcore during circadian rhythm with aging. The cosinor analysis showed no differences between strains and ages for the acrophase. An age effect on the SHR strain (SHR16 < SHR72) was observed regarding the amplitude. SHR16 had higher values regarding MESOR compared to WIS16 and WKY16. In addition, WIS72 and WKY72 showed higher values than WIS16 and WKY16, respectively. Finally, no differences were observed in the strength rhythm analysis. CONCLUSIONS: SHR presented impaired thermoregulatory control at only 16 weeks of age when showing a higher body temperature during the activity phase, while other circadian rhythm parameters showed no differences across aging. Therefore, in taking our results as a whole we can conclude that WIS and WKY are appropriate Wistar strains to be used as normotensive controls for SHR.

ß-hydroxy-ß-methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue.

The effects of resistance training (RT) associated with calcium ß-hydroxyß-methylbutyrate (CaHMB) supplementation on the body composition and gene expression of cytokines related to skeletal muscle hypertrophy and adipose tissue metabolism were studied in rats. Male Wistar rats were divided into four groups of 12 animals: sedentary control (SC); sedentary supplemented (SS); resistance training control (RTC) and resistance training supplemented (RTS). Rats from RTC and RTS groups were submitted to an RT programme and those from SS and RTS groups received 1 mL of CaHMB (320 mg kg-1 day-1) by gavage, for 8 weeks. We evaluated: body composition; plasma lipid profile; the gene expression of interleukin (IL)-6, IL-10, IL-15 and fibronectin type III domain-containing protein 5 (FNDC-5) in skeletal muscle, and IL-6, mitochondrial uncoupling protein 1 (UCP-1) in white adipose tissue (WAT); and the concentration of irisin in WAT. Compared to RTC alone, the combination of CaHMB with RT (RTS) further reduced abdominal circumference (5.3%), Lee index (2.4%), fat percentage (24.4%), plasma VLDL cholesterol (16.8%) and triglycerides (17%) and increased the gene expression of FNDC-5 (78.9%) and IL-6 (47.4%) in skeletal muscle and irisin concentration (26.9%) in WAT. Neither RT nor CaHMB affected the protein percentage or the gene expression of IL-6 and UCP-1 in WAT and IL-10, IL-15 in skeletal muscle. In conclusion, CaHMB supplementation increased the beneficial effects of RT on body fat reduction and was associated with muscular genic expression of IL-6 and FNDC-5 and irisin concentration in WAT, despite the lack of change in protein mass and maximal strength.

Effects of exercise training and stem cell therapy on the left ventricle of infarcted rats.

INTRODUCTION AND OBJECTIVES: Stem cell therapy and aerobic exercise are non-pharmacological therapies following myocardial infarction. The aim of this study was to test whether aerobic exercise training enhances the benefits of mesenchymal stem cell (MSC) therapy on remodeling of the extracellular matrix and fetal gene expression in the left ventricle of infarcted rats. METHODS: Myocardial infarction was surgically induced in six-week old male Wistar rats. Animals were divided into four groups: sedentary control (SC) and sedentary and stem cell treated (SCMSC); exercised (EX) and exercised and stem cell treated (EXMSC). Bone marrow-derived MSCs were immediately transplanted via the tail vein (concentration: 1×106 cells). Exercise training (five days/week, 60 min/day; 60% of maximal running speed) started 24 hours after myocardial infarction and lasted for 12 weeks. RESULTS: Exercise capacity was higher in exercised than in sedentary groups. Animals in the SCMSC, EX and EXMSC groups exhibited better cardiac function than those in SC. Collagen content was lower in the SCMSC, EX and EXMSC groups than in SC and skeletal α-actin expression was lower in EX and EXMSC than in SC. The α/ß-MHC ratio was higher in EX and EXMSC than in SC. The combination of therapies further reduced collagen content in the remote region of the infarct (∼24%) and skeletal α-actin expression (∼30%). CONCLUSION: Aerobic exercise training appears to enhance the beneficial effects of stem cell therapy on remodeling of the extracellular matrix and fetal gene expression in the left ventricle of rats with moderate infarction.

Could pre-infection exercise training improve the efficacy of specific antiparasitic chemotherapy for Chagas disease?

Considering a potential exercise-drug interaction, we investigated whether exercise training could improve the efficacy of specific antiparasitic chemotherapy in a rodent model of Chagas disease. Wistar rats were randomized into five groups: sedentary and uninfected (CT); sedentary and infected (SI); sedentary, infected and treated (SIT); trained and infected (TI); trained, infected and treated (TIT). After 9-weeks running training, the animals were infected with T. cruzi and followed up for 4 weeks, receiving 100 mg kg-1 day-1 benznidazole. No evidence of myocarditis was observed in CT animals. TI animals exhibited reduced parasitemia, myocarditis, and reactive tissue damage compared to SI animals, in addition to increased IFN-γ, IL-4, IL-10, heart non-protein antioxidant (NPA) levels and glutathione-s transferase activity (P < 0.05). The CT, SIT and TIT groups presented similar reductions in parasitemia, cytokines (IFN-γ, TNF-α, IL-4, IL-10, IL-17 and MCP-1), inflammatory infiltrate, oxidative heart damage and antioxidant enzymes activity compared to SI and TI animals, as well as reduced heart microstructural remodeling (P < 0.05). By modulating heart inflammation and redox metabolism, exercise training exerts a protective effect against T. cruzi infection in rats. However, the antiparasitic and cardioprotective effects of benznidazole chemotherapy are more pronounced, determining similar endpoints in sedentary and trained T. cruzi-infected rats.

Spontaneously hypertensive rats have greater impairments in regulating abdominal temperature than brain cortex temperature following physical exercise.

This study aimed to evaluate the changes in brain (Tbrain) and abdominal (Tabd) temperatures in spontaneously hypertensive rats (SHRs) following fatiguing exercise. Male normotensive Wistar rats (NWRs) and SHRs were used at 16 weeks of age. Their arterial pressure was measured by tail plethysmography prior to the experiments to confirm the hypertensive status of the SHRs. Then, the rats underwent implantation of an abdominal temperature sensor to measure Tabd and a guide cannula in the frontal cortex to enable the insertion of a thermistor to measure Tbrain. After a familiarization period, each animal was subjected to incremental speed exercises until fatigue in either a temperate (25 °C) or warm (32 °C) environment, followed by a 60-min post-exercise period at the same temperature at which they exercised. Tbrain, Tabd and tail-skin temperature (Tskin) were measured every min throughout the experiments. SHRs exhibited higher Tabd values than NWRs, and these higher values were transiently and persistently observed at 25 °C and 32 °C, respectively. For example, at 32 °C, Tabd was 0.84 °C higher in SHRs at the 25th min (large effect size). In contrast, regardless of the ambient temperature, SHRs exhibited similar Tbrain values as NWRs, indicating preserved Tbrain regulation following exercise in hypertensive rats. SHRs presented higher Tskin during the last half of the post-exercise period at 25 °C, whereas no inter-group differences were observed at 32 °C. In conclusion, the present results highlight that SHRs, an animal model that mimics uncontrolled essential hypertension in humans, exhibited greater impairments in regulating Tabd than Tbrain during the post-exercise period.

Concomitant exercise training attenuates the cardioprotective effects of pharmacological therapy in a murine model of acute infectious myocarditis.

When administered alone, preinfection exercise training and benznidazole-based chemotherapy induce cardioprotection in Chagas disease. However, the effect of concomitant exercise and benznidazole treatment is unknown. We investigated whether exercise and specific chemotherapy could interact to modulate parasitemia, inflammation, redox status and heart damage in a murine model of T. cruzi infection. Wistar rats were randomized into an uninfected control group (CNT) and four groups infected with T. cruzi: sedentary untreated (SUN) and treated (STR), and trained untreated (TUN) and treated (TTR). Running training was administered 5 days/week for 4 weeks. Treated animals concomitantly received 100 mg/kg/day benznidazole. Heart inflammation and reactive damage were not detected in CNT animals. Compared to SUN, TUN animals presented increased levels of parasitemia, myocarditis, nitric oxide, hydrogen peroxide, protein carbonyl, malondialdehyde, cytokines (IFN-γ, TNF-α, IL-4, IL-6, IL-10 and IL-17), catalase, superoxide dismutase and glutathione reductase activity, as well as reduced heart non-protein antioxidant levels (P < 0.05). TTR animals exhibited higher levels of parasitemia, myocarditis, hydrogen peroxide, malondialdehyde, IFN-γ, TNF-α and IL-6 than STR animals (P < 0.05), which showed the lowest levels of all analyzed parameters compared to the other groups (P < 0.05). Our findings indicate that exercise aggravates acute infection. When concomitantly administered with benznidazole, exercise training impaired parasitic control and chemotherapy-induced cardioprotection in T. cruzi-infected rats. Considering that exercise training and T. cruzi infection constitute independent metabolic challenges, the negative effects of concomitant treatment are potentially related to the overlapping oxidative and immunoinflammatory demands of exercise and the infection itself.

El hambre oculta y la fibromialgia: Una revisión sistemática / The hidden hunger and fibromyalgia: A systematic review

RESUMEN Recientemente há sido discutida la posibilidad de una relación causal entre la fibromialgia (FM) y la deficiencia de micronutrientes, un tipo de deficiencia nutricional conocida como "hambre oculta". Sin embargo, los estudios son pocos y los resultados controversiales, lo que genera debates sobre la influencia real del "hambre oculta" en el proceso de la enfermedad en las personas con fibromialgia. En está revisión se presentan y discuten evidencias científicas relacionadas con la deficiencia de micronutrientes y FM, destacando los principales micronutrientes relacionados. El levantamiento de información fue realizado en los bases de datos de PubMed y Science Direct en estudios observacionales publicados entre los años 2000 y 2017. Fueron seleccionados 14 estudios, ocho dirigidos a la asociación de la deficiencia de vitamina D y la presencia de FM y seis enfocados en la asociación de la deficiencia de minerales con FM. Se sugiere una relación entre la deficiencia de vitamina D y el aumento de la sensibilidad al dolor en la FM. Aunque esa insuficiencia también está asociada a otras enfermedades muscoesqueléticas crónicas. Además, parece que la deficiencia mineral (p.ej.o., hierro, magnesio, zinc y calcio) también desempeña un papel importante en el inicio de la FM y sus principales síntomas.

ABSTRACT Recently the possibility of a causal link between fibromyalgia (FM) and micronutrient deficiency, a type of malnutrition known as "hidden hunger", has been suggested. However, the results are controversial, which raises questions and debates on the actual influence of "hidden hunger" on the development of FM. In this review, we present and discuss scientific evidence related to micronutrient deficiencies and FM, highlighting key micronutrients involved. We searched PubMed and Science Direct databases for all observational studies published between 2000 to March 2017. We selected fourteen observational studies, eight studies aimed at linking vitamin D deficiency to the presence of FM and six studies focused on the association of mineral deficiency with FM. The association between vitamin D deficiency and increased pain sensitivity in FM is suggested, although such insufficiency is also associated with other chronic musculoskeletal disorders. It appears that mineral deficiency (e.g., iron, magnesium, manganese, zinc and calcium) plays an important role in the onset of FM and its main symptoms.

Swim training attenuates the adverse remodeling of LV structural and mechanical properties in the early compensated phase of hypertension.

AIM: Investigate to what extent low-intensity swim training for six weeks counterbalances the adverse remodeling due to the advance of pathological hypertrophy in the left ventricle (LV) structural and mechanical properties in the early compensated phase of hypertension in male SHR. MAIN METHODS: Four-month-old male SHR and Wistar rats were randomly divided into Sed (sedentary) and Ex (exercised) groups. The exercised rats were submitted to a swimming protocol (1h/day, 5times/week, no additional load) for six weeks. LV tissue and isolated myocytes were used to assess structural and mechanical properties. Myocytes were stimulted at frequencies (F) of 1 and 3Hz at 37°C. KEY FINDINGS: Exercised SHR showed improvement in cardiovascular parameters compared to sedentary SHR (mean arterial pressure: 13.22%; resting HR: 14.28.%). About structural and mechanical properties, swim training induced a decrease in LV myocyte thickness (10.85%), number of inflammatory cells (21.24%); collagen type III (74.23%) and type I (85.6%) fiber areas; amplitude of single myocyte shortening (47% to F1 and 28.46% to F3), timecourses of shortening (16.5% to F1 and 7.55% to F3) and relaxation (15.31% to F3) compared to sedentary SHR. SIGNIFICANCE: Six weeks of swim training attenuates the adverse remodeling of LV structural and mechanical properties in the early compensated phase of hypertension in male SHR.