The effects of dietary nitrate ingestion on physical performance tests in 50-65 years old postmenopausal women: A pilot randomized, double-blind, placebo-controlled, and crossover study.

BACKGROUND & AIMS: The post-menopausal period represents a noteworthy stage in a woman's life characterized by hormonal shifts that can influence diverse biological processes encompassing energy metabolism and physical performance. NO3- effects on physical performance in 50-65 years old postmenopausal women after short-term supplementation remain unknown. METHODS: This is a randomized, double-blind, placebo-controlled, crossover study. After two sessions in non-consecutive days of familiarization tests, fifteen post-menopausal women aged between 50 and 65 were enrolled in this study. The trial consisted of two eight-day arms: a) NO3- -70 mL of beetroot juice (BRJ) with ˜400 mg of NO3-, and b) placebo (PLA) -70 mL of BRJ NO3- depleted. Both interventions were obtained from the same manufacturer's product, presenting the same organoleptic properties. After this period, five physical performance tests (handgrip strength, arm curl, sit-to-stand, agility and dynamic balance and 6-min walk test (6MWT)) were applied. RESULTS: Fourteen participants completed all experimental protocols, including a minimum seven-day washout period between protocols. NO2- plasma concentrations were consistently elevated in the NO3- condition at 0.41 (0.40) µM compared to the PLA at 0.18 (0.18) µM (p < 0.001). The 6MWT showed higher values in BRJ with NO3- condition (19.6 m [95%CI: 1.33 to 37.88]; p = 0.038), while the other physical performance tests did not show significant difference between conditions (p > 0.05). CONCLUSIONS: Our findings suggest benefits in the physical performance of activities with longer durations, indicating that the adaptation caused by ingestion of NO3- may be related to the cardiorespiratory capacity.

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.

The anterior cingulate cortex and its interface with the dorsal periaqueductal grey regulating nitric oxide-mediated panic-like behaviour and defensive antinociception.

The anterior cingulate cortex (ACC) Cg1 (24b) area modulates glutamate-mediated unconditioned fear and antinociception organised by hypothalamus. However, it remains unknown whether 24b area also modulates these latter defensive responses through connections with the dorsal periaqueductal grey matter (dPAG), a midbrain structure implicated in the genesis of innate fear-induced defence. The aim of this work is to examine the correlation between the behavioural effects of intra-ACC microinjections of vehicle, NMDA (1 nmol) or lidocaine (2%) with Fos protein expression and nitrergic activity in the dPAG of male C57BL/6 mice that were threatened by snakes. In addition, the 24b area-dPAG pathways were also characterised by neural tract tracing procedures. Finally, the effect of dPAG pretreatment with the neuronal nitric oxide synthase inhibitor N(omega)-propyl-l-arginine (NPLA; 0.2, 0.4 or 0.8 nmol) 10 min before 24b area treatment with NMDA on behavioural and nociceptive responses of threatened mice was studied. The activation of 24b area N-methyl-d-aspartic acid receptors facilitated escape and freezing rather than risk assessment, and enhanced Fos expression and nitrite levels in dPAG, while lidocaine decreased escape and risk assessment as well as Fos and nitrergic activity in dPAG. In addition, dPAG pretreatment with NPLA suppressed intra-24b NMDA-facilitated panicogenic effects while increased nociception. Infusions of an antegrade neurotracer into 24b area showed axonal fibres surrounding both dorsomedial and dorsolateral PAG perikarya. Neurons were identified in 24b area after deposits of a retrograde neurotracer into dPAG. Our findings suggest that the ACC/24b area modulates innate defensive responses through the recruitment of dPAG nitrergic neurons.

Nitrate-rich beet juice intake on cardiovascular performance in response to exercise in postmenopausal women with arterial hypertension: study protocol for a randomized controlled trial.

BACKGROUND: There is no evidence of the use of beetroot juice with a previously recommended dose of nitrate (NO3) (> 300 mg) on the cardiovascular performance during and recovery following exercise in postmenopausal women with systemic arterial hypertension (SAH). METHODS: We will investigate the effects of beetroot juice rich in NO3 acutely (800 mg) and during a week with daily doses (400 mg) on blood pressure, heart rate (HR), cardiac autonomic control, endothelial function, inflammatory, hormonal, and stress biomarkers oxidative stress and enzymes involved in nitric oxide synthesis and mitochondrial regulation, under resting conditions, as well as mediated by submaximal aerobic exercise sessions. Through a randomized, crossover, triple-blind, placebo-controlled clinical trial, 25 physically inactive women with SAH will undergo an acute and 1-week trial, each with two intervention protocols: (1) placebo and (2) beetroot, in which will ingest beet juice with or without NO3 in its composition with a 7-day washout interval. On collection days, exercise will be performed on a treadmill for 40 min at a speed corresponding to 65-70% of VO2peak. The collection of variables (cardiovascular, autonomic, and blood samples for molecular analyses) of the study will take place at rest (135 min after ingestion of the intervention), during exercise (40 min), and in the effort recovery stage (during 60 min) based on previously validated protocols. The collections were arranged so that the measurement of one variable does not interfere with the other and that they have adequate intervals between them. DISCUSSION: The results of this research may help in the real understanding of the nutritional compounds capable of generating safety to the cardiovascular system during physical exercise, especially for women who are aging and who have cardiovascular limitations (e.g., arterial hypertension) to perform physical exercise. Therefore, our results will be able to help specific nutritional recommendations to optimize cardiovascular health. TRIAL REGISTRATION: ClinicalTrials.gov NCT05384340. Registered on May 20, 2022.

Low load strength training, associated with or without blood flow restriction increased NO production and decreased production of reactive oxygen species in rats aorta.

Studies have shown that strength training (ST) with blood flow restriction (BFR) in which low load is used (20-50% of 1 maximum voluntary contraction - MVC) can produce positive adaptations similar to ST with loads equal to or greater than 70% 1 MVC. Furthermore, recent studies have investigated the effects of STBFR on muscle adaptations, but few studies investigated the effects of STBFR on vascular function. This study aimed to evaluate the effects of the STBFR program on the vascular reactivity of the abdominal aorta of Wistar rats with femoral arteriovenous blood flow restriction. Male rats were divided into four groups: sedentary sham (S/S), sedentary with blood flow restriction (S/BFR), trained sham (T/S), and trained with blood flow restriction (T/BFR). The animals in the S/BFR and T/BFR groups underwent surgery to BFR in the femoral artery and vein. After one week, the trained groups started the ST which consisted of climbing ladder, six sets of 10 repetitions with 50% of 1 MVC assessed by maximum loaded weight (MLW) carried out for four weeks. Concentration-response curves to Acetylcholine (ACh: 10 nM - 100 µM) and Phenylephrine (PHE: 1 nM - 30 µM) were performed in aortic rings with intact endothelium. The production of nitric oxide (NO) and reactive oxygen species (ROS) in situ and the vascular remodeling marker (MMP-2) were also measured. The ST increased the strength of the T/S and T/BFR groups in MLW tests. The S/BFR group showed a 22% reduction in relaxation to acetylcholine, but exercise prevented this reduction in the T/BFR group. In animals without BFR, ST did not alter the response to acetylcholine. An increase in NO production was seen in T/S and T/BFR showed a reduction in ROS production (62% and 40%, respectively). In conclusion low load ST with BFR promotes similar vascular function responses to ST without BFR. Low load ST with and without BFR is interventions that can improve performance with similar magnitudes. Both training methods could have some benefits for vascular health due to NO production in the aorta increased in the T/S group and decreased production of reactive oxygen species in the T/BFR group.

Moderate-intensity exercise training improves long-term memory in fructose-fed rats

Abstract Aim: Animal disease model studies are widely used to show the effectiveness of physical exercise to improve cognitive function. Thus far, few studies are investigating the effects of exercise training on memory performance in fructose feed animals. Method: The present study investigated the effects of physical exercise protocol carried out with three weekly sessions, on the short and long-term memory performance of animals fed with fructose. Male Wistar rats were divided into sedentary (SD); sedentary+fructose (SDF); trained (TR); trained+fructose (TRF). Treadmill running sessions consisted of a five-minute warm-up at 20% maximum speed (MS) followed by 40 minutes at 40% MS and a 5-minute cool-down at 20% MS. Sessions were carried out three days a week (Monday, Wednesday, and Friday) for six weeks. Object Recognition Test was used to evaluate short and long-term memory. Results: The access to fructose altered food intake and drinking volume, as fructose-fed animals had lower food intake (SDF: -27% and TRF: -24%) and higher drinking volume (SDF: +49% and TRF: +45%) than an animal which drank water. Trained groups had lower epididymal fat pad compared to their sedentary counterparts (TR: -30% and TRF: -11%). In addition, TR and TRF had an improvement in glucose tolerance. Regarding memory performance, neither fructose intake nor exercise training influenced short-term memory. On the other hand, long-term memory was enhanced by exercise training. An improvement of about 39% was observed for TR and the largest effect was seen for TRF, which improved long-term memory in 76%. Conclusion: In conclusion, moderate-intensity exercise training, carried out three days a week, for six weeks was effective to improve long-term memory in fructose-fed rats. This result was related neither to the visceral fat amount nor to the glucose metabolism. Further studies should considerer the investigation regarding cerebral areas, associated with memory that might be adapted facing physical exercise.