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Objective: Impaired parasympathetic modulation increases the risk for sudden death in patients with heart diseases. Therefore, cholinergic stimulation may have a potential protective role. The aim of this study was to verify the effects of pyridostigmine bromide, a reversible cholinesterase inhibitor, on heart rate (HR), blood pressure (BP), HR and BP variability, and baroreflex sensitivity (BS). Methods: Male Wistar rats were divided in two groups: (1) treated with pyridostigmine in drinking water (7 days, n=10; PYR) and (2) a control group (n=12; CTR). BP was recorded in freely moving rats, and HR and BP variability were quantified by the standard deviation (S.D.) of the mean values during a 30-min period and by spectral analysis. BS was assessed by the ratio between pulse interval and BP power spectra (spontaneous BS) and also by the changes on HR produced by phenylephrine and sodium nitroprusside-induced BP changes. Results: Treated rats had a PYR intake of 7.91±1.90 mg/day (≈31 mg/kg/day). There were no differences between groups concerning resting HR (P=0.158), systolic BP (P=0.481), and BP variability (P=0.201). On the other hand, treatment with PYR increased HR variability on the time domain (S.D.—PYR: 13.5±5.3 ms vs. CTR: 9.9±3.6 ms; P=0.034) and frequency domain (Total power—PYR: 208.3±157.7 ms2 vs. CTR: 109.2±65.6 ms2; P=0.030). BS was also augmented with PYR for both the spontaneous method (High frequency band—PYR: 2.55±1.06 ms/mm Hg vs. CTR: 1.85±0.60 ms/mm Hg; P=0.033) and the drug-induced reflex bradycardia (PYR: 2.48±1.02 bpm/mm Hg vs. CTR: 1.54±0.58 bpm/mm Hg; P=0.024) and reflex tachycardia (PYR: 4.08±1.04 bpm/mm Hg vs. CTR: 2.95±1.30 bpm/mm Hg; P=0.037). Conclusions: In conclusion, treatment with pyridostigmine increased HR variability and BS in normal rats with no modifications on basal hemodynamic parameters. Considering that reduced HR variability and baroreflex sensitivity are independent risk factors in heart disease, the present results support the concept that cholinergic stimulation with pyridostigmine may become a therapeutic option for vagal dysfunction. [Copyright &y& Elsevier]

Bisphenol S (BPS) is widely used in the manufacture products and increase the risk of cardiovascular diseases. The effect of the association between obesity and BPS on cardiac outcomes is still unknown. Male C57BL/6 mice were divided into standard chow diet (SC; 15 kJ/g), standard chow diet + BPS (SCB), high-fat diet (HF; 21 kJ/g), and high-fat diet + BPS (HFB). Over 12 weeks, the groups were exposed to BPS through drinking water (dose: 25 μg/kg/day) and/or a HF diet. We evaluated: body mass (BM), total cholesterol, systolic blood pressure (SBP), left ventricle (LV) mass, and cardiac remodeling. In the SCB group, BM, total cholesterol, and SBP increase were augmented in relation to the SC group. In the HF and HFB groups, these parameters were higher than in the SC and SCB groups. Cardiac hypertrophy was evidenced by augmented LV mass and wall thickness, and ANP protein expression in all groups in comparison to the SC group. Only the HFB group had a thicker LV wall than SCB and HF groups, and increased cardiomyocyte area when compared with SC and SCB groups. Concerning cardiac fibrosis, SCB, HF, and HFB groups presented higher interstitial collagen area, TGFβ, and α-SMA protein expression than the SC group. Perivascular collagen area was increased only in the HF and HFB groups than SC group. Higher IL-6, TNFα, and CD11c protein expression in all groups than the SC group evidenced inflammation. All groups had elevated CD36 and PPARα protein expression in relation to the SC group, but only HF and HFB groups promoted cardiac steatosis with increased perilipin 5 protein expression than the SC group. BPS exposure alone promoted cardiac remodeling with pathological concentric hypertrophy, fibrosis, and inflammation. Diet-induced remodeling is aggravated when associated with BPS, with marked hypertrophy, alongside fibrosis, inflammation, and lipid accumulation. [Display omitted] • Bisphenol S increases systolic blood pressure. • Bisphenol S promotes cardiac hypertrophy, fibrosis, and inflammation. • High-fat diet-induced cardiac hypertrophy is worsened by Bisphenol S exposure. [ABSTRACT FROM AUTHOR]

Tributyltin (TBT) is an organotin compound that has several adverse health effects, including the development of obesity. Although obesity is strongly associated with adipose redox imbalance, there is a lack of information on whether TBT promotes a pro-oxidative environment in WAT. Thus, adult male Wistar rats were randomly exposed to either vehicle (ethanol 0.4%) or TBT (1000 ng/kg) for 30 days. Body and fat pad masses, visceral fat morphology, lipid peroxidation, protein carbonylation, redox status markers, and catalase activity were evaluated. TBT promoted increased adiposity and visceral fat, with hypertrophic adipocytes, but did not alter body mass and subcutaneous fat. ROS production and lipid peroxidation were elevated in TBT group, as well as catalase protein expression and activity, although protein oxidation and glutathione peroxidase protein expression remained unchanged. In conclusion, this is the first study to demonstrate that subacute TBT administration leads to visceral adipose redox imbalance, with increased oxidative stress. This enlights the understanding of the metabolic toxic outcomes of continuous exposure to TBT in mammals. • TBT promotes white adipose tissue dysfunction. • TBT increases adipose oxidative stress. • TBT upregulates the adipose antioxidant defense. [ABSTRACT FROM AUTHOR]

Approximately 12–18% of hypertensive patients are diagnosed with resistant hypertension (RH). The risk of having worse cardiovascular outcomes is twice higher in those patients. The low effectiveness of conventional antihypertensive drugs in RH emphasizes the need to evaluate complementary drug therapies to achieve blood pressure (BP) control. Previous studies have demonstrated that phosphodiesterase 5 (PDE-5) inhibitors improve hemodynamics and reduce BP on essential hypertension. So, the authors aimed to summarize current clinical trials-based evidence published concerning the use of PDE-5 inhibitors on BP, cardiovascular function, and hemodynamics of patients with RH. We searched MEDLINE, EMBASE, LILACS, ClinicalTrials.gov , and WHO International Clinical Trials Registry databases on May 15th, 2020 using pre-defined search terms. Two independent reviewers assessed and extracted data from clinical trials that evaluated the effect of PDE-5 inhibitors on BP. We have included five articles in this systematic review. Four of them developed a single-day protocol, while one has developed a 14-day study. The main findings indicate that PDE-5 inhibitors ameliorate BP, vascular hemodynamics, and diastolic function parameters. Some data demonstrated improvement of endothelial function, but it was not a consensus. The side effects seemed to be limited and well-tolerated. In brief, our systematic review highlights the potential of PDE-5 inhibitors as a therapeutic alternative in addition to the multiple-drug regime for RH. Larger studies are still needed to determine whether the beneficial effects of PDE-5 inhibitors on RH would be maintained with chronic administration. [Display omitted] • Acute use of PDE-5 inhibitors reduced blood pressure in resistant hypertension (RH). • Acute and 14-days use of PDE-5 inhibitors improved diastolic dysfunction in RH. • 14-days treatment also increased cGMP and decreased BNP-32 plasma concentrations. • The side effects seemed to be limited and well-tolerated in all trials. • PDE-5 inhibitors seem to be a potential complementary drug in treatment for RH. [ABSTRACT FROM AUTHOR]

Background: Elevated serum uric acid has been associated with a variety of cardiovascular disease and with inflammation, but these have been little explored in chronic kidney disease (CKD). Elevated uric acid levels are common in CKD patients and could be involved in inflammatory milieu; our aim was to analyze the association between uric acid and inflammatory markers in hemodialysis (HD) patients. Design: This was a cross-sectional study. Setting: This study was conducted from private clinic, Rio de Janeiro, Brazil. Patients: This study included 50 HD patients and 21 healthy subjects. Methods and procedures: This study included 50 HD patients [62% men, 54.3 ± 12.6 years, 57.5 ± 50.1 months on dialysis, and body mass index (BMI), 24.4 ± 4.1 kg/m2] and 21 healthy individuals (45% men, 50.7 ± 15.7 years and BMI, 25.5 ± 4 kg/m2). Uric acid was measured using uricase-PAP method; inflammatory [tumor necrosis factor-alpha (TNF- α), interleukin-6 (IL-6), C-reactive protein (CRP)] and atherosclerosis markers [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1)] were measured by a multiplexed assay. Results: Patients presented high levels of TNF- α, IL-6, CRP, VCAM-1, ICAM-1 (5.5 ± 2.1 pg/mL, 4.1 ± 1.6 pg/mL, 0.32 ± 0.30 mg/mL, 48.5 ± 8.5 ng/mL, 20.5 ± 15.9 ng/mL, respectively), compared with healthy individuals (2.4 ± 1.1 pg/mL, 2.7 ± 0.4 pg/mL, 0.11 ± 0.12 mg/mL, 23.8 ± 5.5 ng/mL, 7.2 ± 1.2 ng/mL, respectively) ( p < 0.04). Uric acid levels were also higher in HD patients (5.4 ± 1.3 mg/dL) than in healthy individuals (3.9 ± 0.9 mg/dL) ( p < 0.02). There was a positive correlation between uric acid and inflammatory markers, IL-6 ( r = 0.30, p = 0.01), CRP ( r = 0.37, p = 0.003), TNF- α ( r = 0.40, p = 0.001), ICAM-1 ( r = 0.53, p = 0.0001), and VCAM-1 ( r = 0.45, p = 0.0001). Conclusion: These original data suggest that uric acid may have a role in inflammation and atherosclerosis in HD patients. However, further prospective studies involving intervention trials should be conducted in order to search for actual causality relationship between these markers. [ABSTRACT FROM AUTHOR]

Summary The purpose of this study was to determine whether exercise modulates the responses of middle cerebral artery blood velocity (MCA Vmean) and cerebrovascular conductance to sympathetic stimulation (i.e. cold pressor test - CPT). To accomplish this, MCA Vmean responses were assessed during CPT, static handgrip exercise (HG) at 30% of maximum voluntary contraction and combined condition (HG + CPT), assigned in a counterbalanced order, in eight healthy subjects. Blood pressure (BP), cardiac output (CO) and end-tidal partial pressure of carbon dioxide (PETCO2) were also measured non-invasively, and an index of vascular conductance was calculated for MCA (CVCi). BP increased from rest ( P<0·05) during CPT and HG and was additionally augmented during HG + CPT ( P<0·05 versus rest, CPT and HG). Despite the greater augmentation in BP during HG + CPT, MCA Vmean was similarly increased during both HG (18·5 ± 2%, P<0·05 versus rest) and combined condition (19·6 ± 2%, P<0·05 versus rest). MCA Vmean remained unchanged from rest during CPT only. CVCi was slightly reduced ( P<0·05) from rest during HG but was greatly reduced by CPT ( P<0·05 versus rest). The reduction in CVCi evoked by CPT at rest (−15 ± 2%, P<0·05 versus rest) was significantly attenuated during HG (−8 ± 2%, P<0·05 versus CPT). Increases in CO were similar in all trials, and PETCO2 was unchanged from rest throughout the experiments. In summary, the cerebral conductance index decreases during the cold pressure test while that reduction is smaller when the CPT is conducted during the HG. This was critical for the maintenance of MCA Vmean during combined condition. [ABSTRACT FROM AUTHOR]

Background: The importance of vagal tone on cardiac function and cardiovascular mortality is well established. Although the presence of an enhanced cardiac vagal tone (CVT) is frequently diagnosed using the 12-lead resting electrocardiogram (ECG) in daily practice, most of the proposed criteria have been determined on an empirical basis. Our objective was to evaluate the effects of pharmacological blockade of the parasympathetic component of the autonomic nervous system on resting ECG tracings. Methods: Nine healthy young adults (24±5 year-old) underwent parasympathetic blockade with atropine sulfate i.v. (0.04 mg kg−1) and resting ECGs were obtained before and 15 min thereafter. CVT was assessed by a dimensionless index, which measures the RR interval reduction caused by the vagal withdrawal induced by a 4-s exercise test performed on a cycle ergometer where the subjects pedal as fast as possible with no added resistance. Results: This index was 1.63±0.24 and 1.03±0.03, before and after atropine, respectively (P<0.0001). Atropine reduced the R–R intervals (P<0.0001), and the amplitude of T-waves in several leads (DII: P=0.03; V4: P=0.04; V5: P=0.03; V6: P=0.01), and abolished the appiculation of T-waves, J-point and ST-segment elevations (P<0.05), and U-waves (P<0.05), which were present in baseline ECG in all subjects in at least two leads. The R-wave amplitude in leads V4, V5, and V6 (all P≥0.10) was not modified by atropine infusion. Conclusion: The duration of the R-R intervals and the amplitude of T-waves in leads DII, V4, V5, and V6, and the presence of T-wave appiculation, U-waves, and elevation of J-point and ST-segment should be used to detect enhanced cardiac vagal tone in healthy subjects. [Copyright &y& Elsevier]

New Findings: What is the central question of this study?What are the mechanisms underlying the cardiac protective effect of aerobic training in the progression of a high fructose‐induced cardiometabolic disease in Wistar rats?What is the main finding and its importance?At the onset of cardiovascular disease, aerobic training activates the p‐p70S6K, ERK and IRβ–PI3K–AKT pathways, without changing the miR‐126 and miR‐195 levels, thereby providing evidence that aerobic training modulates the insulin signalling pathway. These data contribute to the understanding of the molecular cardiac changes that are associated with physiological left ventricular hypertrophy during the development of a cardiovascular disease. During the onset of cardiovascular disease (CVD), disturbances in myocardial vascularization, cell proliferation and protein expression are observed. Aerobic training prevents CVD, but the underlying mechanisms behind left ventricle (LV) hypertrophy are not fully elucidated. The aim of this study was to investigate the mechanisms by which aerobic training protects the heart from LV hypertrophy during the onset of fructose‐induced cardiometabolic disease. Male Wistar rats were allocated to four groups (n = 8/group): control sedentary (C), control training (CT), fructose sedentary (F) and fructose training (FT). The C and CT groups received drinking water, and the F and FT groups received d‐fructose (10% in water). After 2 weeks, the CT and FT rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min/day, 4 days/week). After 10 weeks, LV morphological remodelling, cardiomyocyte apoptosis, microRNAs and the insulin signalling pathway were investigated. The F group had systemic cardiometabolic alterations, which were normalised by aerobic training. The LV weight increased in the FT group, myocardium vascularisation decreased in the F group, and the cardiomyocyte area increased in the CT, F and FT groups. Regarding protein expression, total insulin receptor β‐subunit (IRβ) decreased in the F group; phospho (p)‐IRβ and phosphoinositide 3‐kinase (PI3K) increased in the FT group; total‐AKT and p‐AKT increased in all of the groups; p‐p70S6 kinase (p70S6K) protein was higher in the CT group; and p‐extracellular signal‐regulated kinase (ERK) increased in the CT and FT groups. MiR‐126, miR‐195 and cardiomyocyte apoptosis did not differ among the groups. Aerobic training activates p‐p70S6K and p‐ERK, and during the onset of a CVD, it can activate the IRβ–PI3K–AKT pathway. [ABSTRACT FROM AUTHOR]

The aim of this paper is to assess the integrated responses of ambulatory blood pressure (BP), cardiac autonomic modulation, spontaneous baroreflex sensitivity (BRS), and vascular reactivity after a single bout of resistance exercise (RE) in men with stage 2 hypertension who have never been treated before. Ten hypertensive men were subjected to a RE session of three sets of 20 repetitions and an intensity of 40% of the 1-repetition maximum (RM) test in seven different exercises. For the control (CTR) session, the volunteers were positioned on the exercise machines but did not perform any exercise. Forearm blood flow was measured by venous occlusion plethysmography. We also analyzed the heart rate variability (HRV), ambulatory BP, blood pressure variability (BPV), and BRS. All measurements were performed at different timepoints: baseline, 20 min, 80 min, and 24 h after both RE and CTR sessions. There were no differences in ambulatory BP over the 24 h between the RE and CTR sessions. However, the area under the curve of diastolic BP decreased after the RE session. Heart rate (HR) and cardiac output increased for up to 80 and 20 min after RE, respectively. Similarly, forearm blood flow, conductance, and vascular reactivity increased 20 min after RE (p < 0.05). In contrast, HRV and BRS decreased immediately after exercise and remained lower for 20 min after RE. We conclude that a single bout of RE induced an increase in vascular reactivity and reduced the pressure load by attenuating AUC of DBP in hypertensive individuals who had never been treated with antihypertensive medications. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to investigate the effect of inspiratory muscle training (IMT) on, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress, in older women. Methods: Fourteen elderly women were assigned to perform IMT at 50% of maximal inspiratory pressure (MIP) (IMT group, n = 8) or placebo training at 5% MIP (Sham group, n = 6), in a counter-balanced order, using an inspiratory threshold device for 4 weeks. During the protocol, MIP was tested weekly once. In a second visit, blood pressure, heart rate, stroke volume, cardiac output, middle cerebral artery blood flow velocity (MCAv), and ventilation parameters were recorded continuously at rest and during orthostatic stress testing, which was conducted on a force plate to measure center-of-pressure (COP) oscillations (postural balance) and the electromyographic activity of the right medial gastrocnemius and tibialis anterior. Results: IMT increased MIP from second to 4th week. The drops in MCAv, stroke volume, and cardiac output, as well as COP displacements during initial orthostasis decreased post-IMT. Conclusion: IMT improves the interplay of the respiratory pump, hemodynamic, cerebrovascular and postural balance responses during orthostatic stress in older women. [ABSTRACT FROM AUTHOR]

Overactivation of the classical arm of the renin-angiotensin (Ang) system (RAS) occurs during inflammation, oxidative stress and obesity-induced cardiomyopathy. The activation of the protective arm of RAS may act to counterbalance the deleterious effects of the classical RAS. Although aerobic exercise training (AET) shifts the balance of the RAS towards the protective arm, little is known about the molecular adaptations to different volumes of AET. The aim of this study was to evaluate the impact of AET volume on the modulation of RAS, as well as on cardiac biomarkers of oxidative stress and inflammation, in a diet-induced obesity model. Male Wistar rats were fed either control (CON) or high fat (HF) diet for 32 weeks. At week 20, HF group was subdivided into sedentary, low (LEV, 150 min/week) or high (HEV, 300 min/week) exercise volume. After 12 weeks of exercise, body mass gain, systolic blood pressure and heart rate were evaluated, as well as RAS, oxidative stress and inflammation in the heart. Body mass gain, systolic blood pressure and heart rate were higher in HF group when compared with SC group. Both trained groups restored systolic blood pressure and heart rate, but only HEV reduced body mass gain. Regarding the cardiac RAS, the HF group exhibited favoring of the classical arm and both trained groups shifted the balance towards the counterregulatory protective arm. The HF group had higher B1R expression and lower B2R expression than the control group, and B2R expression was reverted in both trained groups. The HF group also presented oxidative stress. The LEV and HEV groups improved the cardiac redox status by reducing Nox 2 and nitrotyrosine expression, but only the LEV group was able to increase the antioxidant defense by increasing Nrf2 signaling. While the HF group presented higher TNF-α, IL-6 and NFκB expression, and lower IL-10 expression, than the SC group, both training protocols improved the inflammatory profile. Although both trained groups improved the deleterious changes related to obesity cardiomyopathy, it is clear that the molecular mechanisms differ between them. Our results suggest that different exercise volumes might reach different molecular targets, and this could be a relevant factor when using exercise to manage obesity. • Obesity increased cardiac inflammation, oxidative stress and ACE/AT1R activation. • 12 weeks of two different exercise volume protocols were tested for its benefits on the heart. • Both training volumes reduced Nox2 expression, nitrosative damage, and inflammation. • Increased Nrf2 signaling was observed with 150 min, but not 300 min of weekly exercise. • Higher exercise volume favored the alternative arm of renin angiotensin system. [ABSTRACT FROM AUTHOR]

Abstract Introduction In vitro and animal model studies have demonstrated that oscillatory shear can trigger vascular hemostasis and remodeling. However, the roles of hemodynamic forces in vascular human biology are not well understood. This study aimed to determine the effects of increasing oscillatory shear stress (OSS) on coagulation/fibrinolysis factors and matrix metalloproteinase-9 activity in healthy subjects. Materials and methods Ten healthy males (35 ± 7 years) underwent a 30-minute dominant forearm cuff occlusion (75 mm Hg) to exacerbate OSS in the brachial artery. Blood flow was quantified (Doppler ultrasound), and plasma samples were obtained from both arms at rest and during the last 30 s of cuff occlusion on the dominant arm. A proximal cuff (40 mm Hg, close to axilla) was also occluded to facilitate venous blood biomarker trapping. Results The retrograde shear rate and oscillatory shear index were increased and the mean shear rate, mean blood velocity, and mean blood flow were decreased in the cuffed arm (p < 0.05 vs. baseline and non-cuffed arm). Cuff occlusion induced increases in platelet microparticle release (p = 0.05 vs. baseline), prothrombin time (p < 0.05 vs. baseline and non-cuffed arm), tissue plasminogen activator (p < 0.01 vs. baseline and non-cuffed arm), plasminogen activator inhibitor-1 (p < 0.02 vs. baseline and non-cuffed arm), and matrix metalloproteinase-9 activity (p = 0.01 vs. baseline). No significant changes were found in the non-cuffed arm throughout the protocol. Conclusions Exacerbation of OSS induced in vivo disturbances in platelet microparticle release, coagulation-fibrinolysis, and matrix metalloproteinase-9 activity in healthy individuals. These are potential mechanisms involved in OSS-mediated endothelial dysfunction. Highlights • Oscillatory shear stress (OSS) was exacerbated in 10 healthy individuals. • Increased OSS induced platelet microparticle release and abnormal fibrinoylsis. • OSS impaired coagulation cascade activation. • OSS exacerbation increased matrix metalloproteinase-9 activity. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Regular exercise is recommended as a non-pharmacological approach for the prevention and treatment of metabolic syndrome. However, the impact of different combinations of intensity, duration and frequency of exercise on metabolic syndrome and microvascular density has not been reported., What is the main finding and its importance? We provide evidence on the impact of aerobic exercise dose on metabolic and microvascular alterations in an experimental model of metabolic syndrome induced by high-fat diet. We found that the exercise frequency and duration were the main factors affecting anthropometric and metabolic parameters and microvascular density in the skeletal muscle. Exercise intensity was related only to microvascular density in the heart., We evaluated the effect of the frequency, duration and intensity of exercise training on metabolic parameters and structural capillary density in obese rats with metabolic syndrome. Wistar-Kyoto rats were fed either a standard commercial diet (CON) or a high-fat diet (HFD). Animals that received the HFD were randomly separated into either a sedentary (SED) group or eight different exercise groups that varied according to the frequency, duration and intensity of training. After 12 weeks of aerobic exercise training, the body composition, aerobic capacity, haemodynamic variables, metabolic parameters and capillary density in the heart and skeletal muscle were evaluated. All the exercise training groups showed reduced resting systolic blood pressure and heart rate and normalized fasting glucose. The minimal amount of exercise (90 min per week) produced little effect on metabolic syndrome parameters. A moderate amount of exercise (150 min per week) was required to reduce body weight and improve capillary density. However, only the high amount of exercise (300 min per week) significantly reduced the amount of body fat depots. The three-way ANOVA showed a main effect of exercise frequency and duration for the improvement of metabolic syndrome and capillary density in skeletal muscle. Exercise intensity was a main factor in reversing microvascular rarefaction in the heart. [ABSTRACT FROM AUTHOR]

Metabolic syndrome is a cluster of metabolic risk factors that is linked to central obesity, elevated blood pressure, insulin resistance (IR), and dyslipidemia, where the renin-angiotensin system (RAS) may provide a link among them. This study aimed to evaluate volume exercise effects comparing low vs. high volume of chronic aerobic exercise on RAS axes in skeletal muscle in a diet-induced obesity (DIO) rat model. For this, male Wistar-Kyoto rats were fed a standard chow (SC) diet or a high-fat (HF) diet for 32 wk. Animals receiving the HF diet were randomly divided into low exercise volume (LEV, 150 min/wk) and high exercise volume (HEV, 300 min/wk) at the 20th week. After 12 wk of aerobic treadmill training, the body mass and composition, blood pressure, glucose and lipid metabolism, RAS axes, insulin signaling, and inflammatory pathway were performed. HEV slowed the body mass gain, reduced intra-abdominal fat pad and leptin levels, improved total and peripheral body composition and inflammatory cytokine, reduced angiotensin II type 1 receptor expression, and increased Mas receptor protein expression compared with the HF animals. Sedentary groups (SC and HF) presented lower time to exhaustion and maximal velocity compared with the LEV and HEV groups. Both exercise training groups showed reduced resting systolic blood pressure and heart rate, improved glucose tolerance, IR, insulin signaling, and lipid profile. We conclude that the HEV, but not LEV, shifted the balance of RAS toward the ACE2/Mas receptor axis in skeletal muscle, presenting protective effects against the DIO model. [ABSTRACT FROM AUTHOR]

End-to-end anastomosis in the treatment for bile duct injury during laparoscopic cholecystectomy has been associated with stricture formation. The aim of this study was to experimentally investigate the effect of oral tamoxifen (tmx) treatment on fibrosis, collagen content and transforming growth factor-β1, -β2 and -β3 expression in common bile duct anastomosis of pigs. Twenty-six pigs were divided into three groups [sham ( n = 8), control ( n = 9) and tmx ( n = 9)]. The common bile ducts were transected and anastomosed in the control and tmx groups. Tmx (40 mg/day) was administered orally to the tmx group, and the animals were euthanized after 60 days. Fibrosis was analysed by Masson's trichrome staining. Picrosirius red was used to quantify the total collagen content and collagen type I/ III ratio. mRNA expression of transforming growth factor ( TGF)-β1, -β2 and -β3 was quantified using real-time polymerase chain reaction ( qRT- PCR). The control and study groups exhibited higher fibrosis than the sham group, and the study group showed lower fibrosis than the control group ( P = 0.011). The control and tmx groups had higher total collagen content than the sham group ( P = 0.003). The collagen type I/ III ratio was higher in the control group than in the sham and tmx groups ( P = 0.015). There were no significant differences in the mRNA expression of TGF-β1, -β2 and -β3 among the groups ( P > 0.05). Tmx decreased fibrosis and prevented the change in collagen type I/ III ratio caused by the procedure. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress poses a new pathological mechanism for metabolic-associated fatty liver disease (MAFLD). MAFLD treatment has encompassed renin-angiotensin system (RAS) blockers and aerobic exercise training, but their association with hepatic ER stress is not well known. Therefore, we aimed to compare the effects of hepatic RAS modulation by enalapril and/or aerobic exercise training over ER stress in MAFLD caused by a diet-induced obesity model. C57BL/6 mice were fed a standard-chow (CON, n = 10) or a high-fat (HF, n = 40) diet for 8 weeks. HF group was then randomly divided into: HF (n = 10), HF + Enalapril (EN, n = 10), HF + Aerobic exercise training (AET, n = 10), and HF + Enalapril+Aerobic exercise training (EN + AET, n = 10) for 8 more weeks. Body mass (BM) and glucose profile were evaluated. In the liver, ACE and ACE2 activity, morphology, lipid profile, and protein expression of ER stress and metabolic markers were assessed. Both enalapril and aerobic exercise training provided comparable efficacy in improving diet-induced MAFLD through modulation of RAS and ER stress, but the latter was more efficient in improving ER stress, liver damage and metabolism. This is the first study to evaluate pharmacological (enalapril) and non-pharmacological (aerobic exercise training) RAS modulators associated with ER stress in a diet-induced MAFLD model. HF diet led to favoring of the RAS classical arm and increased ER stress through higher expression of the eIF2α pathway. These results could be related to HF diet-associated insulin resistance and upregulation of gluconeogenesis enzymes PEPCK and G6Pase, as well as lipid accumulation through increased lipogenic transcription factor SREBP1c and lower PPARα levels. Enalapril treatment, aerobic exercise training, and the combination of both interventions were able to favor the RAS counterregulatory arm, improve ER stress and decrease lipid accumulation. All interventions were also able to improve insulin resistance, although aerobic exercise training showed more efficiency, reverting glucose intolerance and decreasing the expression of PEPCK. Aerobic exercise training was also the only intervention able to reduce binucleation of hepatocytes and the association with enalapril treatment reverted the increase in hepatocytes with two or more nuclei, which could be suggestive of liver damage associated with the pharmacological treatment. [Display omitted] • Enalapril and aerobic exercise training decrease ACE/ACE2 ratio in obese mice. • RAS counterregulatory arm could be associated to decreased ER stress markers in MAFLD. • Aerobic exercise training better improved liver ER stress markers, metabolism and damage. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum (ER) stress poses a new pathological mechanism for metabolic-associated fatty liver disease (MAFLD). MAFLD treatment has encompassed renin-angiotensin system (RAS) blockers and aerobic exercise training, but their association with hepatic ER stress is not well known. Therefore, we aimed to compare the effects of hepatic RAS modulation by enalapril and/or aerobic exercise training over ER stress in MAFLD caused by a diet-induced obesity model. C57BL/6 mice were fed a standard-chow (CON, n = 10) or a high-fat (HF, n = 40) diet for 8 weeks. HF group was then randomly divided into: HF (n = 10), HF + Enalapril (EN, n = 10), HF + Aerobic exercise training (AET, n = 10), and HF + Enalapril+Aerobic exercise training (EN + AET, n = 10) for 8 more weeks. Body mass (BM) and glucose profile were evaluated. In the liver, ACE and ACE2 activity, morphology, lipid profile, and protein expression of ER stress and metabolic markers were assessed. Both enalapril and aerobic exercise training provided comparable efficacy in improving diet-induced MAFLD through modulation of RAS and ER stress, but the latter was more efficient in improving ER stress, liver damage and metabolism. This is the first study to evaluate pharmacological (enalapril) and non-pharmacological (aerobic exercise training) RAS modulators associated with ER stress in a diet-induced MAFLD model. HF diet led to favoring of the RAS classical arm and increased ER stress through higher expression of the eIF2α pathway. These results could be related to HF diet-associated insulin resistance and upregulation of gluconeogenesis enzymes PEPCK and G6Pase, as well as lipid accumulation through increased lipogenic transcription factor SREBP1c and lower PPARα levels. Enalapril treatment, aerobic exercise training, and the combination of both interventions were able to favor the RAS counterregulatory arm, improve ER stress and decrease lipid accumulation. All interventions were also able to improve insulin resistance, although aerobic exercise training showed more efficiency, reverting glucose intolerance and decreasing the expression of PEPCK. Aerobic exercise training was also the only intervention able to reduce binucleation of hepatocytes and the association with enalapril treatment reverted the increase in hepatocytes with two or more nuclei, which could be suggestive of liver damage associated with the pharmacological treatment. [Display omitted] • Enalapril and aerobic exercise training decrease ACE/ACE2 ratio in obese mice. • RAS counterregulatory arm could be associated to decreased ER stress markers in MAFLD. • Aerobic exercise training better improved liver ER stress markers, metabolism and damage. [ABSTRACT FROM AUTHOR]

Abstract: Background: Chronic Kidney Disease (CKD) patients present high levels of electronegative LDL (LDL−) that can modulate the expression of molecules involved in inflammation and it is closely linked to atherosclerosis. We investigated the association between LDL(−) and inflammatory markers in patients undergoing hemodialysis (HD). Methods: Forty-seven HD patients from a private clinic in Rio de Janeiro, Brazil were studied and compared with 20 age matched healthy individuals. Serum LDL(−) and anti-LDL(−) autoantibody levels were measured by ELISA; TNF-α, IL-6, VCAM-1 and ICAM-1 were determined by a multiplex assay kit. Results: HD patients presented higher IL-6 and TNF-α concentrations (4.1±1.6 and 5.5±2.1pg/ml, respectively) than healthy subjects (2.6±0.2 and 2.4±1.1pg/ml, respectively) (p=0.0001). In addition, they presented higher VCAM-1 and ICAM-1 levels and, LDL(−) concentrations were also increased (0.18±0.12U/l) when compared to healthy individuals (0.10±0.08U/l) (p<0.02). In contrast, the anti-LDL(−) autoantibody levels were lower in HD patients (0.02±0.01mg/l) than in healthy subjects (0.05±0.03mg/l) (p<0.001). There was a positive correlation between LDL(−) and IL-6 (r=0.25, p=0.004) and ICAM-1 (r=0.36; p=0.003). There was also a negative correlation between anti-LDL(−) autoantibodies and TNF-α (r=−0.37; p=0.003) and VCAM-1 (r=−0.50; p=0.0001). Conclusions: The association between LDL(−) and inflammation and the lower levels of anti-LDL(−) autoantibodies are important risk factors related to atherosclerosis in CKD. [Copyright &y& Elsevier]

The article offers information on the study conducted by the authors related to association among polymorphisms in endothelial nitric oxide gene and parasympathetic adaptation induced by exercise. It states that 183 healthy people from the Military Police Academy of Sao Paulo, Brazil were invited out of which 75 were excluded due to muscle injury. It mentions that genomic DNA of the 80 subjects were extracted from circulating leucocytes and genotypes were identified through polymerase chain reaction. It highlights that exercise training did not change body mass index (BMI) and there was variability in the autonomic adaptation to the training.

The renin-angiotensin (Ang) system (RAS) is a complex hormonal system present locally in several tissues such as cardiovascular organs. RAS deregulation through overactivation of the classical arm [Ang-converting enzyme (ACE)/Ang-II/Ang type 1 receptor (AT1R)] has been linked to the development of cardiovascular diseases and activation of endoplasmic reticulum (ER) stress pathways. The ER stress is a condition that, if unresolved, might lead to heart failure, atherosclerosis, hypertension, and endothelial dysfunction. Accumulated evidence has shown that the RAS modulates the UPR activation. Several studies reported increased ER stress markers in response to Ang-II treatment, in both in vivo and in vitro models. Evidence has also pointed that targeting the RAS classical arm through RAS blockers, gene silencing or genetic models leads to lower levels of ER stress markers. Few studies demonstrated protective effects of the counter-regulatory arm (ACE-2/Ang-(1-7)/Mas receptor) over ER stress. However, the crosstalk mechanisms between the arms of the RAS and ER stress remain unclear. In this review, we sought to explore the classical arm of the RAS as a key mechanism in UPR activation and to suggest a possible protective role of the counter-regulatory arm in mitigating ER stress. [Display omitted] • Ang-II leads to endoplasmic reticulum (ER) stress through diverse mechanisms. • Blocking the renin-angiotensin system (RAS) classic arm leads to lower ER stress. • The RAS counter-regulatory arm may exert protection against ER stress. [ABSTRACT FROM AUTHOR]

Anabolic androgenic steroid (AAS) abuse has become a public health problem in many countries, and is associated with many psychiatric disorders. Epidemiological studies have also found increasing numbers of sleep disorders reported by individuals using AASs. The purpose of this study was to evaluate sleep patterns and disorders in anabolic androgenic users who practice resistance exercise. The sample comprised 58 males divided into three groups: (1) 20 current AAS users aged 26 ± 1.2, (2) 21 controls with no history of AAS use, aged 26 ± 1 and (3) 17 sedentary men with no sleep disorders aged 27.2 ± 0.34. The volunteers spent a night in the sleep laboratory for polysomnography. Comparing the three groups, the user group showed reduced sleep efficiency and more wakings after sleep onset than the sedentary group ( P = 0.001). The sedentary group showed a higher percentage of stage 4 than the non-users group. We suggest that using of anabolic steroids reduced sleep efficiency and alters sleep architecture. [ABSTRACT FROM AUTHOR]

Anabolic androgenic steroid (AAS) abuse has become a public health problem in many countries, and is associated with many psychiatric disorders. Epidemiological studies have also found increasing numbers of sleep disorders reported by individuals using AASs. The purpose of this study was to evaluate sleep patterns and disorders in anabolic androgenic users who practice resistance exercise. The sample comprised 58 males divided into three groups: (1) 20 current AAS users aged 26 +/- 1.2, (2) 21 controls with no history of AAS use, aged 26 +/- 1 and (3) 17 sedentary men with no sleep disorders aged 27.2 +/- 0.34. The volunteers spent a night in the sleep laboratory for polysomnography. Comparing the three groups, the user group showed reduced sleep efficiency and more wakings after sleep onset than the sedentary group (P = 0.001). The sedentary group showed a higher percentage of stage 4 than the non-users group. We suggest that using of anabolic steroids reduced sleep efficiency and alters sleep architecture. [ABSTRACT FROM AUTHOR]

• Cardiac output drop at initial orthostasis was reduced by acute inspiratory load. • Acute inspiratory load enhances cerebrovascular regulation during initial orthostatis. • Postural control was improved by acute inspiratory load during initial orthostatis. • Postural control enhancement could help to prevent falls in the elderly population. The acute inspiratory resistive load (IRL) may increase the respiratory pump contributes to hemodynamic responses during orthostatic stress. However, IRL effects on cerebrovascular and postural control interplay is unknown. Fourteen older women (65 ± 4 years) performed two orthostatic tests with spontaneous breathing through acute experimental (−9 cm.H 2 O) or sham load impedance (0 cmH 2 O) connected to a pneumotachograph for breath-by-breath recordings on a facemask. Both tests were executed on a force plate, for postural balance analysis, and electromyographic activity records of calf muscles. Blood pressure, middle cerebral artery blood velocity (MCAv), heart rate (HR), stroke volume (SV), and cardiac output (CO) were continuously recorded. IRL reduced postural instability in the first five seconds at orthostatic position compared to sham. Although the mean blood pressure and MCAv were similar in both conditions, IRL reduced the SV and CO drops, and time to recover MCAv. Therefore, IRL improved postural control, CO and MCAv responses during initial orthostasis. [ABSTRACT FROM AUTHOR]

To compare the effect of 150 min vs. 300 min of weekly moderate intensity exercise training on the activation of the opioid system and apoptosis in the hearts of a diet-induced obesity model. Male Wistar rats were fed with either control (CON) or high fat (HF) diet for 32 weeks. At the 20th week, HF group was subdivided into sedentary, low (LEV, 150 min·week−1) or high (HEV, 300 min·week−1) exercise volume. After 12 weeks of exercise, body mass gain, adiposity index, systolic blood pressure, cardiac morphometry, apoptosis biomarkers and opioid system expression were evaluated. Sedentary animals fed with HF presented pathological cardiac hypertrophy and higher body mass gain, systolic blood pressure and adiposity index than control group. Both exercise volumes induced physiological cardiac hypertrophy, restored systolic blood pressure and improved adiposity index, but only 300 min·week−1 reduced body mass gain. HF group exhibited lower proenkephalin, PI3K, ERK and GSK-3β expression, and greater activated caspase-3 expression than control group. Compared to HF, no changes in the cardiac opioid system were observed in the 150 min·week−1 of exercise training, while 300 min·week−1 showed greater proenkephalin, DOR, KOR, MOR, Akt, ERK and GSK-3β expression, and lower activated caspase-3 expression. 300 min·week−1 of exercise training triggered opioid system activation and provided greater cardioprotection against obesity than 150 min·week−1. Our findings provide translational aspect with clinical relevance about the critical dose of exercise training necessary to reduce cardiovascular risk factors caused by obesity. [ABSTRACT FROM AUTHOR]