Effects of oral HPΒCD-angiotensin-(1-7) supplementation on recreational mountain bike athletes: a crossover study.

BACKGROUND: Supplementation with Angiotensin-(1-7) [(Ang-1-7)] has received considerable attention due to its possible ergogenic effects on physical performance. The effects of a single dose of Ang-(1-7) on the performance of mountain bike (MTB) athletes during progressive load tests performed until the onset of voluntary fatigue have previously been demonstrated. This study tested the effects of Ang-(1-7) in two different exercise protocols with different metabolic demands: aerobic (time trial) and anaerobic (repeated sprint). METHODS: Twenty one male recreational athletes were given capsules containing an oral formulation of HPßCD-Ang-(1-7) (0.8 mg) and HPßCD-placebo (only HPßCD) over a 7-day interval; a double-blind randomized crossover design was used. Physical performance was examined using two protocols: a 20-km cycling time trial or 4 × 30-s repeated all-out sprints on a leg cycle ergometer. Data were collected before and after physical tests to assess fatigue parameters, and included lactate levels, and muscle activation during the sprint protocol as evaluated by electromyography (EMG); cardiovascular parameters: diastolic and systolic blood pressure and heart rate; and performance parameters, time to complete (time trial), maximum power and mean power (repeated sprint). RESULTS: Supplementation with an oral formulation of HPßCD-Ang-(1-7) reduced basal plasma lactate levels and promoted the maintenance of plasma glucose levels after repeated sprints. Supplementation with HPßCD-Ang-(1-7) also increased baseline plasma nitrite levels and reduced resting diastolic blood pressure in a time trial protocol. HPßCD-Ang-(1-7) had no effect on the time trial or repeat sprint performance, or on the EMG recordings of the vastus lateralis and vastus medialis. CONCLUSIONS: Supplementation with HPßCD-Ang-(1-7) did not improve physical performance in time trial or in repeated sprints; however, it promoted the maintenance of plasma glucose and lactate levels after the sprint protocol and at rest, respectively. In addition, HPßCD-Ang-(1-7) also increased resting plasma nitrite levels and reduced diastolic blood pressure in the time trial protocol. TRIAL REGISTRATION: RBR-2nbmpbc, registered January 6th, 2023. The study was prospectively registered.

Scale up of implementation of a multidimensional intervention to enhance hypertension and diabetes care at the primary care setting: A protocol for a cluster-randomized study in Brazil.

BACKGROUND: Hypertension and diabetes mellitus (DM) are highly prevalent in low and middle-income countries (LMICs), and the proportion of patients with uncontrolled diseases is higher than in high-income countries. Innovative strategies are required to surpass barriers of low sources, distance and quality of health care. Our aim is to assess the uptake and effectiveness of the implementation of an integrated multidimensional strategy in the primary care setting, for the management of people with hypertension and diabetes mellitus in Brazil. METHODS: This scale up implementation study called Control of Hypertension and diAbetes in MINas Gerais (CHArMING) Project has mixed-methods, and comprehends 4 steps: (1) needs assessment, including a standardized structured questionnaire and focus groups with health care practitioners; (2) baseline period, 3 months before the implementation of the intervention; (3) cluster randomized controlled trial (RCT) with a 12-months follow-up period; and (4) a qualitative study after the end of follow-up. The cluster RCT will randomize 35 centers to intervention (n = 18) or usual care (n = 17). Patients ≥18 years old, with diagnosis of hypertension and/or DM, of 5 Brazilian cities in a resource-constrained area will be enrolled. The intervention consists of a multifaceted strategy, with a multidisciplinary approach, including telehealth tools (decision support systems, short message service, telediagnosis), continued education with an approach to issues related to the care of people with hypertension and diabetes in primary care, including pharmacological and non-pharmacological treatment and behavioral change. The project has actions focused on professionals and patients. CONCLUSIONS: This study consists of a multidimensional strategy with multidisciplinary approach using digital health to improve the control of hypertension and/or DM in the primary health care setting. We expect to provide the basis for implementing an innovative management program for hypertension and DM in Brazil, aiming to reduce the present and future burden of these diseases in Brazil and other LMICs. CLINICAL TRIAL IDENTIFIER: This study was registered in ClinicalTrials.gov. (NCT05660928).

Nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome.

Obesity and metabolic disorders represent a significant global health problem and the gut microbiota plays an important role in modulating systemic homeostasis. Recent evidence shows that microbiota and its signaling pathways may affect the whole metabolism and the Renin-Angiotensin System (RAS), which in turn seems to modify microbiota. The present review aimed to investigate nutritional implications in the mechanistic link between the intestinal microbiome, renin-angiotensin system, and the development of obesity and metabolic syndrome components. A description of metabolic changes was obtained based on relevant scientific literature. The molecular and physiological mechanisms that impact the human microbiome were addressed, including the gut microbiota associated with obesity, diabetes, and hepatic steatosis. The RAS interaction signaling and modulation were analyzed. Strategies including the use of prebiotics, symbiotics, probiotics, and biotechnology may affect the gut microbiota and its impact on human health.

Intermittent high-intensity exercise for pre- to established hypertension: A systematic review and meta-analysis.

OBJECTIVE: To determine the impact of intermittent high-intensity exercise training ([IHIE], including high-intensity interval training [HIIT] and recreational team sports [RTS]) on systolic (SBP) and diastolic blood pressure (DBP) in adults with pre- to established arterial hypertension. DATA SOURCES: MEDLINE, Cochrane Library, Embase, and SPORTDiscus. ELIGIBILITY CRITERIA: Randomized controlled trials (RCTs) comparing the impact of IHIE on BP versus a non-exercise control. DATA COLLECTION AND ANALYSIS: Two authors independently conducted all procedures. Mean differences were calculated using random-effects model. The certainty of the evidence was assessed with GRADE. RESULTS: Twenty-seven RCTs (18 HIIT and 9 RTS) were analyzed, with median duration of 12 weeks. Participants' (n = 946) median age was 46 years. Overall, IHIE decreased SBP (-3.29 mmHg; 95% CI: -5.19, -1.39) and DBP (-2.62 mmHg; 95% CI: -3.79, -1.44) compared to the control group. IHIE elicited higher decreases in office SBP and DBP of hypertensive subjects (SBP: -7.13 mmHg, [95% CI: -10.12, -4.15]; DBP: -5.81 mmHg, [95% CI: -7.94, -3.69]) than pre-hypertensive (SBP: -2.14 mmHg, [95% CI: -4.36, -0.08]; DBP: -1.83 mmHg, [95% CI: -2.99, -0.67]). No significant differences were found between HIIT (SBP: -2.12 mmHg, [95% CI: -4.78, -0.54]; DBP: -1.89 mmHg, [95% CI: -3.32, -0.48]) and RTS (SBP: -4.18 mmHg, [95% CI: -7.19, -2.43]; DBP: -4.04 mmHg, [95% CI: -6.00, -2.09]). These findings present low/very low certainty of evidence. No adverse cardiovascular events were reported. CONCLUSIONS: IHIE appears to be safe and to promote substantial decreases in BP, particularly in patients with hypertension. However, the certainty of evidence was low/very low. PROTOCOL: CRD42020163575.

Phosphate and IL-10 concentration as predictors of long-covid in hemodialysis patients: A Brazilian study.

Background: The global burden of persistent COVID-19 in hemodialysis (HD) patients is a worrisome scenario worth of investigation for the critical care of chronic kidney disease (CKD). We performed an exploratory post-hoc study from the trial U1111-1237-8231 with two specific aims: i) to investigate the prevalence of COVID-19 infection and long COVID symptoms from our Cohort of 178 Brazilians HD patients. ii) to identify whether baseline characteristics should predict long COVID in this sample. Methods: 247 community-dwelling older (>60 years) patients (Men and women) undergoing HD (glomerular filtration rate < 15 mL/min/1.73m2) with arteriovenous fistula volunteered for this study. All patients presented hypertension and diabetes. Patients were divided in two groups: without long-COVID and with long-COVID. Body composition, handgrip strength, functional performance, iron metabolism, phosphate, and inflammatory profile were assessed. Patients were screened for 11-months after COVID-19 infection. Results were considered significant at P < 0.05. Results: We found that more than 85% of the COVID-19 infected patients presented a severe condition during the infection. In our sample, the mortality rate over 11-month follow was relatively low (8.4%) when compared to worldwide (approximately 36%). Long COVID was highly prevalent in COVID-19 survivors representing more than 80% of all cases. Phosphate and IL-10 were higher in the long COVID group, but only phosphate higher than 5.35 mg/dL appears to present an increased prevalence of long COVID, dyspnea, and fatigue. Conclusion: There was a high prevalence of COVID-19 infection and long COVID in HD patients from the Brazilian trial 'U1111-1237-8231'. HD clinics should be aware with phosphate range in HD patients as a possible target for adverse post-COVID events.

Combined training is not superior to strength and aerobic training to mitigate cardiovascular risk in adult healthy men.

Although the beneficial effects of aerobic training on cardiovascular risk factors are evident, the potential beneficial effect of strength and combined training on these risk factors is controversial. This study aimed to evaluate the effect of aerobic and strength training programmes, performed alone or in combination, on cardiovascular risk factors in sedentary, apparently healthy and non-obese adult men. The study was conducted with 37 subjects who were randomly divided into the following groups: aerobic (AG), combined (ASG), strength (SG) and control (CG). The exercise programmes were performed three times a week and lasted approximately 50 minutes. Dietary intake, anthropometry, blood pressure, muscular strength, aerobic capacity, lipid profile and glycaemic control were assessed before and after 12 weeks of the intervention. One-way analysis of variation (ANOVA) for baseline, and ANOVA for repeated measures were used to assess differences between the initial and final time points of the four groups. Changes in blood pressure and glycaemic control were not significant in any of the groups. No differences were observed in LDL-C between training groups. HDL-C increased significantly only in the AG. In conclusion, if minimal changes in the lipid profile are needed, an aerobic training programme can provide possible benefits for HDL-C in apparently healthy and non-obese adult men.

The effect of the protective face mask on cardiorespiratory response during aerobic exercise.

The protective face mask (PFM) has been widely used for safety purposes and, after the advent of the COVID-19 pandemic, its use is growing steadily, not only among healthcare personnel but also the general population. While the PFM is important to preserve the wearer from contaminating agents present in the airflow, they are well known to increase the subjective perception of breathing difficulty. Although some studies have demonstrated that PFM use worsens exercise tolerance, several studies state that there is no such limitation with the use of PFM. Moreover, no serious adverse effects during physical exercise have been found in the literature. Physical exercise represents a significant challenge to the human body through a series of integrated changes in function that involve most of its physiologic systems. In this respect, cardiovascular and respiratory systems provide the capacity to sustain physical tasks over extended periods. Within this scenario, both convective oxygen (O2 ) transport (product of arterial O2 content × blood flow) to the working locomotor muscles and O2 diffusive transport from muscle capillaries to mitochondria are of paramount importance to endurance performance. Interestingly, the effects of PFM on cardiorespiratory response during aerobic exercise depends on the type of mask and exercise (i.e., walking, running, or cycling), the ventilatory demands, arterial oxygen levels, maximal oxygen consumption and endurance performance. The purpose of this review is to elucidate the effect of protective face mask-wearing on (1) cardiorespiratory responses during aerobic exercise and (2) endurance performance.

High-protein diet associated with resistance training reduces cardiac TNF-α levels and up-regulates MMP-2 activity in rats.

The consumption of high-protein diets (HPD) is associated with resistance training (RT) due to effects on metabolism. However, little is known about these effects on cardiac tissue. This study aimed to investigate effects of HPD and RT on cardiac biomarkers. 18 rats were divided into normo-protein (NPD), and HPD groups: NPD-Control, NPD-RT, HPD-Control, and HPD-RT. Interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-a), nitric oxide (NO), activity of metalloproteinase-2 (MMP-2), and vascular factor (VEGF) were analysed. RT was effective in regulating body weight, increasing strength, and reducing food consumption (p < .05). HPD induces higher levels of interleukin 6 (p = .0169), and lowers NO (p < .0001). When associated with RT, the HPD decreases levels of tumour necrosis factor alpha, while enhances NO, and MMP activity (p < .05). The association of RT with HDP decreases inflammatory parameters and indicates an enhancement in the molecular parameters of cardiac tissue.

Increased circulating levels of angiotensin-(1-7) in severely ill COVID-19 patients.

This letter reports an unexpected increase of the ACE2 product angiotensin-(1-7) and a parallel decrease of its substrate angiotensin II, suggesting a dysregulation of the renin-angiotensin system towards angiotensin-(1-7) formation in #COVID19 patients https://bit.ly/3xFXuTU.

Alamandine but not angiotensin-(1-7) produces cardiovascular effects at the rostral insular cortex.

Experiments aimed to evaluate the tissue distribution of Mas-related G protein-coupled receptor D (MrgD) revealed the presence of immunoreactivity for the MrgD protein in the rostral insular cortex (rIC), an important area for autonomic and cardiovascular control. To investigate the relevance of this finding, we evaluated the cardiovascular effects produced by the endogenous ligand of MrgD, alamandine, in this brain region. Mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded in urethane anesthetized rats. Unilateral microinjection of equimolar doses of alamandine (40 pmol/100 nL), angiotensin-(1-7), angiotensin II, angiotensin A, and Mas/MrgD antagonist d-Pro7-Ang-1-7 (50 pmol/100 nL), Mas antagonist A779 (100 pmol/100 nL), or vehicle (0.9% NaCl) were made in different rats (n = 4-6/group) into rIC. To verify the specificity of the region, a microinjection of alamandine was also performed into intermediate insular cortex (iIC). Microinjection of alamandine in rIC produced an increase in MAP (Δ = 15 ± 2 mmHg), HR (Δ = 36 ± 4 beats/min), and RSNA (Δ = 31 ± 4%), but was without effects at iIC. Strikingly, an equimolar dose of angiotensin-(1-7) at rIC did not produce any change in MAP, HR, and RSNA. Angiotensin II and angiotensin A produced only minor effects. Alamandine effects were not altered by A-779, a Mas antagonist, but were completely blocked by the Mas/MrgD antagonist d-Pro7-Ang-(1-7). Therefore, we have identified a brain region in which alamandine/MrgD receptor but not angiotensin-(1-7)/Mas could be involved in the modulation of cardiovascular-related neuronal activity. This observation also suggests that alamandine might possess unique effects unrelated to angiotensin-(1-7) in the brain.

Angiotensin-(1-7)/Mas receptor modulates anti-inflammatory effects of exercise training in a model of chronic allergic lung inflammation.

AIMS: Exercise training increases circulating and tissue levels of angiotensin-(1-7) [Ang-(1-7)], which was shown to attenuate inflammation and fibrosis in different diseases. Here, we evaluated whether Ang-(1-7)/Mas receptor is involved in the beneficial effects of aerobic training in a chronic model of asthma. MATERIAL AND METHODS: BALB/c mice were subjected to a protocol of asthma induced by ovalbumin sensitization (OVA; 4 i.p. injections) and OVA challenge (3 times/week for 4 weeks). Simultaneously to the challenge period, part of the animals was continuously treated with Mas receptor antagonist (A779, 1 µg/h; for 28 days) and trained in a treadmill (TRE; 60% of the maximal capacity, 1 h/day, 5 days/week during 4 weeks). PGC1-α mRNA expression (qRT-PCR), plasma IgE and lung cytokines (ELISA), inflammatory cells infiltration (enzymatic activity assay) and airway remodeling (by histology) were evaluated. KEY FINDINGS: Blocking the Mas receptor with A779 increased IgE and IL-13 levels and prevented the reduction in extracellular matrix deposition in airways in OVA-TRE mice. Mas receptor blockade prevented the reduction of myeloperoxidase activity, as well as, prevented exercise-induced IL-10 increase. These data show that activation of Ang-(1-7)/Mas receptor pathway is involved in the anti-inflammatory and anti-fibrotic effects of aerobic training in an experimental model of chronic asthma. SIGNIFICANCE: Our results support exercise training as a non-pharmacological tool to defeat lung remodeling induced by chronic pulmonary inflammation. Further, our result also supports development of new therapy based on Ang-(1-7) or Mas agonists as important tool for asthma treatment in those patients that cannot perform aerobic training.

Association of physical activity levels and the prevalence of COVID-19-associated hospitalization.

OBJECTIVES: We compared physical activity levels before the outbreak and quarantine measures with COVID-19-associated hospitalization prevalence in surviving patients infected with SARS-CoV-2. Additionally, we investigated the association of physical activity levels with symptoms of the disease, length of hospital stay, and mechanical ventilation. DESIGN: Observational, cross-sectional. METHODS: Between June 2020 and August 2020, we invited Brazilian survivors and fully recovered patients infected with SARS-CoV-2 to respond to an online questionnaire. We shared the electronic link to the questionnaire on the internet. We collected data about clinical outcomes (symptoms, medications, hospitalization, and length of hospital stay) and cofactors, such as age, sex, ethnicity, preexisting diseases, socioeconomic and educational, and physical activity levels using the International Physical Activity Questionnaire (IPAQ short version). RESULTS: Out of 938 patients, 91 (9.7%) were hospitalized due to COVID-19. In a univariate analysis, sex, age, and BMI were all associated with hospitalizations due to COVID-19. Men had a higher prevalence of hospitalization (66.6%, p = 0.013). Patients older than 65 years, obese, and with preexisting disease had a higher prevalence of COVID-19-related hospitalizations. In a multivariate regression model, performance of at least 150 min/wk (moderate) and/or 75 min/wk (vigorous) physical activity was associated with a lower prevalence of hospitalizations after adjustment for age, sex, BMI, and preexisting diseases (PR = 0.657; p = 0.046). CONCLUSIONS: Sufficient physical activity levels were associated with a lower prevalence of COVID-19-related hospitalizations. Performing at least 150 min a week of moderate-intensity, or 75 min a week of vigorous-intensity physical activity was associated with 34.3% reduction in prevalence.

Angiotensin-(1-7) oral formulation improves physical performance in mountain bike athletes: a double-blinded crossover study.

BACKGROUND: The ECA2/Ang-(1-7)/Mas axis is shown to be involved in effects mediated by physical exercise, as it can induce the release of nitric oxide (ON) and bradykinin (BK), which are potent vasodilators. The vasodilating action the NO/BK can contribute to increased metabolic efficiency in muscle tissue and central nervous system. The formulation HPß-CD-Ang-(1-7) through its mechanisms of action can be a promising supplement to aid in the maintenance and improvement of performance and may also favor recovery during competitions. The premise of this study was to investigate the effects of acute oral supplementation HPß-CD-Ang-(1-7) on the performance of mountain bike (MTB) practitioners. METHODS: Fourteen recreational athletes, involved in training programs for at least one year, participated in this crossover design study. Subjects underwent two days of testing with a seven-day interval. HPß-CD-Ang-(1-7) (1.75 mg) and HPßCD-Placebo were provided in capsules three hours prior to tests. To determine the safety of the HPß-CD-Ang-(1-7) formulation associated with physical effort, cardiovascular parameters heart rate (HR) and blood pressure (BP) were analyzed. Physical performance was measured using maximal oxygen uptake (VO2), total exercise time (TET), mechanical work (MW), mechanical efficiency (ME), and rating of perceived exertion (RPE). Respiratory exchange coefficient (REC), lactate and non-esterified fatty acids (NEFAs) were measured. Maximal incremental tests were performed on a progressively loaded leg cycle ergometer. RESULTS: There were no significant differences in terms of HR or BP at rest and maximum effort between the HPß-CD-Ang-(1-7) and placebo groups. The VO2max showed significant differences (p = 0.04). It was higher in the Ang-(1-7)condition (66.15 mlO2.kg- 1.min- 1) compared to the placebo (60.72 mlO2.kg- 1.min- 1). This was also observed for TET (Ang-(1-7) 39.10 min vs. placebo 38.14 min; p = 0.04), MW (Ang-(1-7) 156.7 vs. placebo 148.2; p = 0.04), and at the lowest RPE (Ang-(1-7) vs. placebo; p = 0.009). No significant differences were observed for REC, NEFAs, or Lactate. CONCLUSIONS: These results suggest that HPß-CD-Ang-(1-7) improves the physical performance of MTB recreational athletes and could be a promising supplement. TRIAL REGISTRATION: RBR-2 × 56pw8, registered January 15th, 2021. The study was prospectively registered.

Master athletes have longer telomeres than age-matched non-athletes. A systematic review, meta-analysis and discussion of possible mechanisms.

The aim of this systematic review and meta-analysis was 1) to assess whether master athletes have longer telomeres than age-matched non-athletes and 2) discuss possible underlying mechanisms underlying telomere length preservation in master athletes. A literature search was performed in PubMed, Web of Science, Scopus and SPORTDiscus up to August 2020. Only original articles published in peer-reviewed journals that compared telomere length between master athletes and aged-matched non-athletes were included. Eleven studies fulfilled eligibility criteria and were included in the final analysis. Overall, 240 master athletes (51.9±7.5 years) and 209 age-matched non-athletes (50.1±9.1 years) were analyzed. Master athletes had been participating in high-level competitions for approximately 16.6 years. Pooled analyses revealed that master athletes had longer telomeres than aged-matched non-athletes (SMD=0.89; 95% CI=0.45 to 1.33; p<0.001). Master athletes showed lower pro-oxidant damage (SMD=0.59; 95% CI=0.26 to 0.91; p<0.001) and higher antioxidant capacity (SMD=-0.46; 95% CI=-0.89 to -0.03; p=0.04) than age-matched non-athletes. Further, greater telomere length in master athletes is associated with lower oxidative stress and chronic inflammation, and enhanced shelterin protein expression and telomerase activity. In conclusion, 1) master athletes have longer telomeres than age-matched non-athletes, which may be the result of 2) lower levels of oxidative stress and chronic inflammation, and elevated shelterin expression and telomerase activity.

ACE2 in the renin-angiotensin system.

In 2020 we are celebrating the 20th anniversary of the angiotensin-converting enzyme 2 (ACE2) discovery. This event was a landmark that shaped the way that we see the renin-angiotensin system (RAS) today. ACE2 is an important molecular hub that connects the RAS classical arm, formed mainly by the octapeptide angiotensin II (Ang II) and its receptor AT1, with the RAS alternative or protective arm, formed mainly by the heptapeptides Ang-(1-7) and alamandine, and their receptors, Mas and MrgD, respectively. In this work we reviewed classical and modern literature to describe how ACE2 is a critical component of the protective arm, particularly in the context of the cardiac function, coagulation homeostasis and immune system. We also review recent literature to present a critical view of the role of ACE2 and RAS in the SARS-CoV-2 pandemic.

Maternal obesity modulates both the renin-angiotensin system in mice dams and fetal adiposity.

Obesity is a chronic multifactorial disease and is currently a public health problem. Maternal obesity during pregnancy is more dangerous as it impairs the health of the mother and future generations. Obesity leads to several metabolic disorders. Since white adipose tissue is an endocrine tissue, obesity often leads to disordered secretion of inflammatory, glycemic, lipid and renin-angiotensin system (RAS) components. The RAS represents a link between obesity and its metabolic consequences. Therefore, our goal was to evaluate the possible changes caused by a high-fat diet in RAS-related receptor expression in the uterus and placenta of pregnant mice and determine the underlying effects of these changes in the fetuses' body composition. Breeding groups were formed after obesity induction by high-fat (HF) diet. Dams and fetuses were euthanized on the 19th day of the gestational period. The HF diet effectively induced obesity, glucose intolerance and insulin resistance in mice. Fetuses born from HF dams showed increased body weight and adiposity. Both results were accompanied by increased AT1R expression in placenta and uterus together with increased angiotensin-converting enzyme expression in the uterus and a decreased expression of MAS1 in placenta of HF dams. These results suggest a link between RAS, maternal obesity induced by HF diet and the fetuses' body adiposity. This new path now can be more thoroughly explored.