Effects of dietary inorganic nitrate on blood pressure during and post-exercise recovery: A systematic review and meta-analysis of randomized placebo-controlled trials.

OBJECTIVES: A systematic review with meta-analysis was completed to study the effects of dietary inorganic nitrate (NO3-) oral ingestion from vegetables and salts on blood pressure responses during and following exercise. BACKGROUND: NO3- is a hypotensive agent with the potential to reduce blood pressure peaks during exercise and amplify exercise-induced hypotensive effects. Several randomized and controlled trials have investigated the effects of NO3- on hemodynamic responses to physical exercise, however this still has yet to be studied systematically. METHODS: The searches were conducted on EMBASE, Medline, and SPORTSDiscus databases. The study included masked randomized controlled trials (RCTs) with participants ≥18 years old. The NO3-intervention group received at least 50 mg NO3-/day with similar sources amid NO3- and placebo conditions. Included studies reported systolic blood pressure (SBP) or diastolic blood pressure (DBP) values during or following exercise performance. RESULTS: 1903 studies were identified, and twenty-six achieved the inclusion criteria. NO3- daily dosages ranged from 90 to 800 mg/day. Throughout exercise, SBP had smaller increases in the NO3- group (-2.81 mmHg (95%CI: -5.20 to -0.41), p=0.02. DBP demonstrated lower values in the NO3- group (-2.41 mmHg (95%CI: -4.02 to -0.79), p=0.003. In the post-exercise group, the NO3- group presented lower SBP values (-3.53 mmHg (95%CI: -5.65 to 1.41), p=0.001, while no changes were identified in DBP values between NO3- and placebo groups (p=0.31). Subgroup meta-analysis revealed that SBP baseline values, exercise type, duration of NO3- ingestion, and its dosages mediated blood pressure responses during and following exercise. CONCLUSIONS: NO3- ingestion prior to exercise attenuated the increases in SBP and DBP during exercise, and increased the decline in SBP after exercise. These results are dependent on factors that moderate the blood pressure responses (e.g., health status, type of exercise, resting blood pressure values).

Acute and short-term beetroot juice nitrate-rich ingestion enhances cardiovascular responses following aerobic exercise in postmenopausal women with arterial hypertension: A triple-blinded randomized controlled trial.

BACKGROUND: The increase in blood pressure (BP) levels in the postmenopausal period can be partly explained by the decrease in nitric oxide synthases (NOS). OBJECTIVE: To investigate the acute and one-week effects of beetroot juice nitrate-rich (BRJ-NO3-rich) ingestion on cardiovascular and autonomic performance in response to submaximal aerobic exercise in postmenopausal women with systemic arterial hypertension (SAH) who are physically inactive. METHODS: Fourteen postmenopausal women with SAH [mean (SD) age: 59(4) y; BMI (kg/m2): 29.2(3.1)] completed submaximal aerobic exercise bouts after an acute and a one-week intervention with BRJ in a placebo-controlled, randomized, triple-blind, crossover design. Participants ingested either BRJ (800 mg of NO3-) or placebo acutely and drank either BRJ (400 mg of NO3-) or placebo every day for the next six days. After two and ½ hours, they performed a session of aerobic submaximal aerobic exercise, and their systolic BP (SBP) and diastolic BP (DBP), flow-mediated dilation (FMD), heart rate (HR) recovery, and HR variability were measured. RESULTS: In the post-exercise recovery period, SBP dropped significantly in the BRJ-NO3-rich group (-9.28 mmHg [95%CI: -1.68 to -16.88] ES: -0.65, p = 0.019) compared to placebo after acute ingestion. The FMD values increased after acute BRJ-NO3-rich on post-exercise (3.18 % [0.36 to 5.99] ES: 0.87, p = 0.031). After the one-week intervention, FMD values were higher in the BRJ-NO3-rich group before (4.5 % [1.62 to 7.37] ES: 1.21, p = 0.005) and post-exercise measurements (4.2 % [1.52 to 6.87] ES: 1.22, p = 0.004) vs. placebo. HRV indices with remarkable parasympathetic modulation to heart recovered faster on the BRJ-NO3-rich group than placebo group. No between-group differences were identified in values of HR post-exercise recovery in the 30s, 60s, 120s, 180s, and 300s. CONCLUSIONS: Acute and short-term BRJ-NO3-rich ingestion may enhance cardiovascular and autonomic behavior in response to aerobic exercise in postmenopausal women diagnosed with SAH. CLINICAL TRIAL REGISTRY NUMBER: https://clinicaltrials.gov/ct2/show/NCT05384340.

Negligible Effects of Nutraceuticals from Beetroot Extract on Cardiovascular and Autonomic Recovery Response following Submaximal Aerobic Exercise in Physically Active Healthy Males: A Randomized Trial.

BACKGROUND: There is little evidence that nutraceuticals from beetroot extract are beneficial with regards to recovery of the cardiovascular parameters and the autonomic nervous system (ANS) after submaximal aerobic exercise, though this formulation is employed widely for this purpose. OBJECTIVE: To study the effects of beetroot extract supplementation on the recovery of cardiorespiratory and autonomic parameters after a session of submaximal aerobic exercise. METHODS: Sixteen healthy male adults commenced a cross-over, randomized, double-blind and placebo-controlled trial. Beetroot extract (600 mg) or placebo (600 mg) were ingested 120 min prior to evaluation on randomized days. We assessed systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial pressure (MAP), heart rate (HR) and HR variability (HRV) indexes at Rest and during 60 min of recovery from submaximal aerobic exercise. RESULTS: Beetroot extract ingestion slightly accelerated HR, SBP, DBP and MAP reduction following exercise associated to the placebo protocol (vs. rest). Yet no group effect (p = 0.99) was identified between the beetroot and placebo protocols on HR mean, in addition to interaction (group vs. time) (p = 0.60). No group effect was attained between the SBP (p = 0.90), DBP (p = 0.88), MAP (p = 0.73) and PP (p = 0.99) protocols and no significant differences (group vs. time) were observed between the values of SBP (p = 0.75), DBP (p = 0.79), MAP (p = 0.93) and PP (p = 0.63) between placebo and beetroot protocols. Similarly, the reoccurrence of cardiac vagal modulation after exercise via the HF (ms2) was enhanced, but not with regards to the RMSSD index. No group effect (p = 0.99) was identified for the HF (p = 0.90) and RMSSD (p = 0.67) indices. Likewise, we observed no significant differences (group vs. time) amongst the values of HF (p = 0.69) and RMSSD (p = 0.95) between the placebo and beetroot protocols. CONCLUSION: Whilst beetroot extract might assist the recovery of the cardiovascular and autonomic systems following submaximal aerobic exercise in healthy males, these results seem insignificant owing to minor differences between interventions and are weak clinically.

Exercise training modifies the whole blood DNA methylation profile in middle-aged and older women.

This is a longitudinal single-arm clinical trial aimed to investigate whether exercise training would modify the whole blood methylation profile in healthy women. A total of 45 subjects were engaged in an exercise training protocol during a 14-wk follow up, consisting of aerobic cardiorespiratory and muscle strength exercises. Subjects were evaluated at baseline (PRE), after 7 wk of exercise training (POST 7), and after 14 wk of exercise training (POST 14). Functional primary outcomes included anthropometric, blood pressure, biochemical measurements, physical tests, and global health assessments. Blood samples were collected at each time point to determine the methylation profile using a DNA methylation array technique screening up to 850k different sites. Exercise training decreased blood pressure and triglyceride levels and enhanced physical performance, including upper- and lower-body maximum strength. Moreover, exercise training improved markers of quality of life. In the array analysis, 14 wk of exercise training changed the methylation of more than 800 sites. Across these differentially methylated sites, we found that differentially methylated sites in the promoter region were more hypermethylated after exercise training, suggesting that this hypermethylation process may affect the transcription process. When inputting the differentially methylated sites in pathway analysis, we found several metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling. This study demonstrates that exercise training promotes a robust change in the whole blood methylation profile and provides new insights into the key regulators of exercise-induced benefits.NEW & NOTEWORTHY We have shown that exercise training lowers blood pressure and triglyceride levels, improves physical performance, and improves quality of life in middle-aged and elderly women. Regarding epigenetic data, we noticed that more than 800 sites are differentially methylated in whole blood after physical training. We emphasize that the differentially methylated sites in the promoter region are more hypermethylated after physical training. In addition, this study shows that key members of metabolic pathways, including AMPK signaling, TGF-ß signaling, and insulin signaling, are among the genes hypermethylated after physical exercise in older women.

Comparison of Periodization Models of Concurrent Training in Recreationally Active Postmenopausal Women.

ABSTRACT: Medeiros, LHL, Sandbakk, SB, Bertazone, TMA, and Bueno Júnior, CR. Comparison of periodization models of concurrent training in recreationally active postmenopausal women. J Strength Cond Res 36(4): 977-983, 2022-Although concurrent training is the most effective way to improve both neuromuscular and cardiorespiratory functions in older populations, there are no studies in the literature comparing different periodization models on cardiorespiratory and muscle strength adaptations. Thus, the main objective of this study was to investigate the effects of different periodization models of concurrent aerobic and strength training using equalized training volume programs on muscle strength and cardiorespiratory fitness in recreationally active postmenopausal women. After 3 weeks of adaptation, 58 women aged 50-75 years were randomly assigned to (a) nonperiodization (NP), (b) daily nonlinear periodization (NLP), or (c) flexible daily NLP (FNLP). At baseline and after 12 weeks, aerobic fitness (peak oxygen uptake [V̇o2peak] and the 6-minute walk test) and maximal muscle strength (1 repetition maximum of bench press and leg press) were measured. It was shown that maximal strength increased in the bench press (effect size [ES] 1.18 in NLP and 1.22 in FNLP) and leg press (ES 0.92 in NLP and 0.89 in FNLP) in the periodized groups-in the NP group, these values were 0.49 and 0.46, respectively. In the 6-minute walk test, aerobic fitness statistically improved in all groups-with an ES of 1.02 in the NP, 1.33 in the NLP, and 0.54 in the FNLP. This study showed that only periodization models (NLP and FNLP) induced a moderate ES in maximal strength, and all groups (NP, NLP, and FNLP) demonstrated improved aerobic fitness evaluated by V̇o2peak and the 6-minute walk test in recreationally active postmenopausal women.

Effects of the COVID-19 pandemic on the global health of women aged 50 to 70 years.

AIM/BACKGROUND: The most recent pandemic caused by the new coronavirus disease (COVID-19) urged dramatic changes in people's lives. Potentially, the COVID-19 pandemic affects physical and mental health as well as behavioral and social aspects. However, the direct impacts of the COVID-19 pandemic on health-related parameters are not yet known. The present study aimed to evaluate the effect of 16 weeks during the COVID-19 pandemic on health-related parameters of physically inactive women aged 50 to 70 years. METHODS: Thirty-four physically inactive women participated in the study. We performed tests to evaluate aerobic capacity and muscle strength, anthropometric measurements, blood pressure (BP), blood parameters, diet, and physical activity levels. All evaluations were carried out before and 16 weeks after the initial phase of the COVID-19 pandemic in Brazil (i.e., from March to July 2020). RESULTS: Systolic BP (p < .0001; effect size (ES) = 0.62), diastolic BP (p < .0001; ES = 0.71), grip strength of the right (p < .05; ES = 0.43) and left hand (p < .05; ES = 0.49), performance in six-minute walk test (p < .05; ES = 0.46), free time physical activity levels (p < .05; ES = 0.40), domestic physical activity levels (p < .05; ES = 0.39), platelet count (p < .0001; ES = 0.48), and mean corpuscular hemoglobin concentration (p < .0001; ES = 1.14) reduced in comparison to the period before the pandemic. In contrast, glycated hemoglobin levels (p < .0001; ES = 0.77), triglycerides (p < .05; ES = 0.40), and insulin levels (p < .05; ES = 0.60) increased in comparison to the period before the pandemic. CONCLUSION: The COVID-19 pandemic negatively impacted the general health status of physically inactive women aged 50 to 70, potentially increasing their susceptibility to comorbidities, such as type 2 diabetes and hypertriglyceridemia.

Fasted condition in multicomponent training does not affect health parameters in physically active post-menopausal women.

Diet and exercise are the main modifiable factors for cardiovascular disease and may be particularly important in older adults. We investigated the effects of fasting during 12 weeks of multicomponent training in the context of the aging process in physically active post-menopausal women. METHOD: 25 women (60.6 ± 8.9 years) were randomized into two groups: fed (FED, n=12) or fasted (FASTED, n=13) and submitted to multicomponent training. The participants underwent anthropometric, body composition, blood pressure, biochemical blood and physical fitness assessments. RESULTS: There was a reduction in both groups for waist circumference [FED: 100.4±6.8 and 99.1±7.1 cm before and after the intervention, respectively; F = 4.214, p = 0.048; FASTED: 93.1±10.2 and 92.2±8.4 cm before and after the intervention, respectively; p = 0.039]. No significant changes were observed for the other outcomes. DISCUSSION: The current research results, the first in the context of aging, agree with previous studies that analyzed chronic effects of fasting, showing that fasted exercise training did not improve anthropometric measurements, body composition, or blood markers compared to the fed condition after long-term exercise training. Together, these findings suggest that fasting during multicomponent training does not affect health parameters in physically active post-menopausal women.

Role of interleukin-6 in inhibiting hepatic autophagy markers in exercised mice.

BACKGROUND: Based on the crosstalk of inflammation with apoptosis, autophagy, and endoplasmic reticulum (ER) stress, the main objective of this study was to explore the role of interleukin-6 (IL-6) on genes and proteins related to these phenomena in the livers of mice submitted to acute exhaustive exercise. METHODS: Reverse transcription-quantitative polymerase chain reaction and immunoblotting technique were used to evaluate the livers of wild-type (WT) and IL-6 knockout (KO) mice at baseline (BL) and 3 h after the acute exhaustive physical exercise (EE). RESULTS: Compared to the WT at baseline, the IL-6 KO had lower exhaustion velocity, mRNA levels of Mtor, Ulk1, Map1lc3b, and Mapk14, and protein contents of ATG5 and p-p70S6K/p70S6K. For the WT group, the EE decreased glycemia, mRNA levels of Casp3, Mtor, Ulk1, Foxo1a, Mapk14, and Ppargc1a, and protein contents of ATG5 and p-p70S6K/p70S6K, but increased mRNA levels of Sqstm1. For the IL-6 KO group, the EE decreased glycemia, mRNA levels of Casp3 and Foxo1a, and protein contents of pAkt/Akt and Mature/Pro IL-1beta, but increased mRNA levels of Sqstm1, and protein contents of p-AMPK/AMPK. CONCLUSION: The inhibition of the hepatic autophagy markers induced by the acute EE was attenuated in IL-6 KO mice, highlighting a new function of this cytokine.

Treinamento de força/sobrecarga mecânica e sinalização do complexo 1 do alvo da rapamicina em mamíferos na hipertrofia muscular em diferentes modelos experimentais: revisão sistemátic / Resistance training/mechanical overload and mammalian target of rapamycin complex 1 signaling on muscle hypertrophy in different experimental

O objetivo deste artigo de revisão sistemática foi apresentar o envolvimento da sinalização de aminoácidos e mecanotransdução na ativação do alvo mamífero de rapamicina do complexo 1 (mTORC1) na musculatura esquelética de animais e a expressão e papel do mTORC1 em humanos submetidos ao treinamento de força/estímulo mecânico. Foi realizada uma busca na base de dados PubMed com as seguintes palavras-chave: mTORC1, mammalian target of rapamycin complex 1, resistance exercise, strength training, mechanical overload e skeletal muscle hypertrophy, amino acid sensing transporter e mechanotransduction. Evidências demonstram que a ativação do mTORC1 possui correlação positiva com a hipertrofia muscular induzida pelo treinamento de força/estímulo mecânico. O mTORC1 integra diversos sinais oriundos de aminoácidos (sinalização de transportadores e sensores) e estímulo mecânico/treinamento de força (mecanotransdução). Ademais, o emprego de modelos de camundongos mutantes, abordagens genéticas, farmacológicas, cultura de células, modelos experimentais de treinamento de força para animais, assim como estudos com humanos, vêm possibilitando a elucidação destes mecanismos moleculares...(AU)

The aim of this systematic review was to provide comprehensive review about mechanotransduction and amino acid signaling in the activation of the mammalian target of rapamycin complex 1 (mTORC1) in animal skeletal muscle and the expression and role of mTORC1 in humans in response to resistance training/mechanical stimulus. PubMed data base was used with the following keywords: mTORC1, mammalian target of rapamycin complex 1, resistance exercise, strength training, mechanical overload and skeletal muscle hypertrophy, amino acid sensing transporter and mechanotransduction. Evidence demonstrates that the activation of the mechanistic target of rapamycin complex 1 (mTORC1) is correlated positively with skeletal muscle hypertrophy induced by resistance training/mechanical stimulus. mTORC1 integrates a myriad of signals coming from amino acids (transporter and sensing mechanisms) and mechanical stimulus/resistance training (mechanotransduction). Moreover, the utilization of mutant mice models, genetic, cell culture and pharmacological tools, experimental resistance exercise rodent models, as well as human studies have been elucidating these molecular mechanisms...(AU)

Aptidão física e nível habitual de atividade física associados à saúde cardiovascular em adultos e idosos / Physical fitness and habitual level of physical activity associated with cardiovascular health in adults and elderly

O nível habitual de atividade física (NHAF) vem sendo utilizado para estabelecer uma relação entre estilo de vida ativo e saúde cardiovascular. No entanto, a avaliação da aptidão física permitiria a avaliação real das condições físicas do indivíduo, podendo assim apresentar melhores relações com a saúde cardiovascular. Objetivos: Relacionar o NHAF e aptidão física com a saúde cardiovascular de adultos e idosos e verificar a associação da prática regular de exercícios físicos supervisionada com os diferentes níveis de aptidão física. Método: Foram avaliados 213 adultos e idosos (> 50 anos) participantes de projetos comunitários. Os participantes realizaram as seguintes avaliações: NHAF por meio do questionário IPAQ, aptidão física por meio de uma bateria de testes motores que permitiu o cálculo do Índice de Aptidão Funcional Geral (IAFG), pressão arterial, perfil lipídico e índice de massa corporal. Resultados: O modelo linear generalizado evidenciou um maior número de diferenças com relação às variáveis relacionadas à saúde cardiovascular quando os participantes foram subdivididos em grupos tendo o IAFG como variável independente, comparado ao NHAF. O teste exato de Fisher evidenciou que os grupos de IAFG classificados como “bom” e “muito bom” apresentaram maior proporção de indivíduos com prática regular de exercícios físicos superior a 6 meses, com destaque para um maior número realizando a prática com supervisão (p<0,0001). Conclusão: O IAFG apresenta melhor associação com a saúde cardiovascular do que o NHAF e o tempo de prática e a supervisão estão associados ao nível de aptidão física...

The habitual level of physical activity (HLPA) has been used to establish the relation between active lifestyle and cardiovascular health. However, the assessment of physical fitness would review the actual physical condition of the individual, and thus can have better relations with cardiovascular health. Objectives: Relate HLPA and physical fitness with cardiovascular health of adults and elderly and to verify the association of supervised regular physical exercise with different levels of fitness. Method: 213 adults and elderly (> 50 years) participating in community projects were evaluated. The HLPA were assessed by the IPAQ and physical fitness through a battery of motor tests that allowed the calculation of the General Functional Fitness Index (GFFI). Blood pressure, lipid profile and body mass index were considered as indicators of cardiovascular health. Results: The generalized linear model showed a greater number of differences with respect to variables related to cardiovascular health when participants were subdivided having GFFI as an independent variable, compared to HLPA. The Fisher exact test showed that the groups GFFI classified as “good” and “very good” showed a higher proportion of individuals with regular practice for more than 6 months exercise, especially for a larger number performing the practice under supervision (p <0.0001). Conclusion: The GFFI has better association with cardiovascular health than HLPA and time of practice and supervision are associated with the level of physical fitness...

Combined effect of AMPK/PPAR agonists and exercise training in mdx mice functional performance.

The present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers are less affected in the course of the disease than glycolitic counterparts. Therefore, a cohort of 34 male congenic C57Bl/10J mdx mice included in this study was randomly assigned into four groups: vehicle solution (V), EM [AICAR (AMPK agonist, 50 mg/Kg-1.day-1, ip) and GW 1516 (PPARδ agonist, 2.5 mg/Kg-1.day-1, gavage)], ET (voluntary running on activity wheel) and EM+ET. Functional performance (grip meter and rotarod), aerobic capacity (running test), muscle histopathology, serum creatine kinase (CK), levels of ubiquitined proteins, oxidative metabolism protein expression (AMPK, PPAR, myoglobin and SCD) and intracellular calcium handling (DHPR, SERCA and NCX) protein expression were analyzed. Treatments started when the animals were two months old and were maintained for one month. A significant functional improvement (p<0.05) was observed in animals submitted to the combination of ET and EM. CK levels were decreased and the expression of proteins related to oxidative metabolism was increased in this group. There were no differences among the groups in the intracellular calcium handling protein expression. To our knowledge, this is the first study that tested the association of ET with EM in an experimental model of muscular dystrophy. Our results suggest that the association of ET and EM should be further tested as a potential therapeutic approach in muscular dystrophies.

Resposta taquicárdica e controle autonômico no exercício físico em modelo genético de insuficiência cardíaca / Tachycardic response and autonomic control in physical exercise in genetic model of cardiac insufficiency

O aumento da atividade nervosa simpática e a taquicardia em repouso ou durante esforços físicos estão associados ao aumento da morbimortalidade, mesmo na ausência de sinais clínicos de doença cardíaca. Sabendo-se da importância dos receptores α2A/α2C-adrenérgicos na modulação da atividade nervosa e frequência cardíaca (FC), o presente trabalho utiliza um modelo genético de cardiomiopatia induzida por excesso de catecolaminas circulantes baseado na inativação gênica dos receptores α2A/α2C-adrenérgicos em camundongos (α2A/α2CKO) para verificar a resposta da FC ao exercício físico (EF), assim como o controle simpatovagal da FC ao EF. Testou-se a hipótese de que haveria resposta taquicárdica exacerbada durante o EF nos camundongos α2A/α2CKO mesmo quando a função cardíaca ainda estivesse preservada em repouso, sendo o receptor α2A-adrenérgico o principal responsável por essa resposta. Camundongos machos da linhagem C57Bl6J, controle (CO) e com inativação gênica para os receptores α2A (α2AKO), α2C α2CKO) e α2A/α2CKO foram submetidos a um teste de tolerância ao esforço físico. Outros dois grupos de camundongos, CO e α2A/α2CKO, foram submetidos ao bloqueio farmacológico dos receptores muscarínicos e β-adrenérgicos e ao EF progressivo para se avaliar a contribuição simpatovagal para a taquicardia de EF. Observou-se intolerância ao esforço físico (1.220 ± 18 e 1.460 ± 34 vs. 2.630 ± 42m, respectivamente) e maior taquicardia ao EF (765 ± 16 e 792 ± 13 vs. 603 ± 18bpm, respectivamente) nos camundongos α2AKO e α2A/α2CKO vs. CO. Além disso, o balanço autonômico estava alterado nos camundongos α2A/α2CKO pela hiperatividade simpática e menor efeito vagal cardíaco. Esses resultados demonstram a importância dos receptores α2A/α2C-adrenérgicos no controle autonômico não só no repouso, mas também durante o EF, sendo o receptor ...

Increase of sympathetic nervous activity and tachycardia at rest or during physical exertions are associated with increase of morbimortality, even in the absence of clinical signs of cardiac disease. Considering the importance of the α2A/α2C-adrenergic receptors in the modulation of the nervous activity and heart rate (HR), the present study uses a genetic model of cardiomyopathy induced by excess of circulating catecholamine in the gene inactivation of the α2A/α2 -adrenergic receptors in mice (α2A/α2CKO) to verify the HR response to physical exercise (PE), as well as the sympathetic-vagal control of the HR to PE. The hypothesis is that there would be exacerbated tachycardic response during PE in α2A/α2CKO mice even when the cardiac function was still preserved at rest, being the α2A-adrenergic receptor the main reason for this response. Male mice of the C57Bl6J lineage, control (CO) and with gene inactivation for the a2A (α2AKO), α2C α2CKO) and α2A/α2CKO receptors were submitted to tolerance to a physical exercise test. Two other groups of mice, CO and α2A/α2CKO, were submitted to pharmacological blocking of the muscarinic and β-adrenergic receptors as well as to progressive PE to assess the sympathetic-vagal contribution to PE tachycardia. Intolerance to physical exercise (1.220 ± 18 and 1.460 ± 34 vs. 2.630 ± 42m, respectively) and higher tachycardia to PE (765 ± 16 e 792 ± 13 vs. 603 ± 18 bpm, respectively) in the α2AKO and α2A/α2CKO vs. CO mice was observed. Moreover, the autonomic balance was altered in the α2A/α2CKO mice by the sympathetic hyperactivity and lower cardiac vagal effect. These outcomes demonstrated the importance of the α2A/α2C-adrenergic receptors in autonomic control not only at rest, but also during PE, being theα2A-adrenergic receptor responsible for the sympathetic hyperactivity and lower ...