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Aging is associated with an increased risk of cardiovascular disease and vascular dysfunction. Reduced nitric oxide bioavailability is considered one of the key mechanisms underlying vascular dysfunction in large arteries of older adults. However, the relationship between cardiovascular disease risk factors, nitric oxide bioavailability, and skeletal muscle microvascular reactivity, an early hallmark in cardiovascular disease progression, is unclear in older individuals. Also uncertain is whether this relationship is influenced by sex. Therefore, this study assessed the association between cardiovascular disease risk factors, circulating markers of nitric oxide availability (plasma nitrate and nitrite), and skeletal muscle microvascular reactivity in older individuals. First, we confirmed in a cohort of young and older individuals that aging is associated with skeletal muscle microvascular dysfunction. Next, we observed that skeletal muscle microvascular reactivity (P = 0.653; η2 = 0.016) and circulating nitric oxide metabolites (Nitrate: P = 0.641, η2 = 0.011; Nitrite: P = 0.560, η2 = 0.017; NOx: P = 0.639, η2 = 0.011) did not differ between older males and females. Finally, using multivariate regression models, we found that: (i) the number of cardiovascular risk factors was negatively associated with skeletal muscle microvascular reactivity in older males and females (B = -0.132, P = 0.044); (ii) the relationship between plasma nitrite and skeletal muscle microvascular reactivity was influenced by sex (F = 6.837, P = 0.016); and (iii) skeletal muscle microvascular reactivity in older females displayed a strong positive association with plasma nitrite (R2 = 0.720, P < 0.001). While the impact of cardiovascular disease risk factors on skeletal muscle microvascular reactivity was not influenced by sex, sex-related discrepancies were found in the relationship between nitric oxide bioavailability and skeletal muscle microvascular reactivity in older individuals.

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Near-infrared spectroscopy combined with vascular occlusion test (NIRS-VOT) is a reactive hyperemia technique for in vivo evaluation of skeletal muscle microvascular reactivity. Previous studies using NIRS-VOT have been shown to be able to detect impairments in microvascular function in high-risk cardiovascular disease populations, such as older individuals. It has been demonstrated that older individuals have slower reactive hyperemia compared with young individuals. Importantly, older individuals also show less desaturation during ischemia compared with young individuals. Based on these findings, it has been suggested that the slower reactive hyperemia observed in older individuals is explained by the lower desaturation during blood flow occlusion (reduced ischemic stimulus). This retrospective analysis compared reactive hyperemia in 36 young and 47 older tissue desaturation-matched individuals that underwent 5-min blood flow occlusion. Overall, we showed that older individuals have impaired reactive hyperemia compared with young when matching for the degree of desaturation and blood flow occlusion time. These findings provide evidence that lower tissue desaturation during ischemia is not a major determinant of impaired reactive hyperemia in older individuals.NEW & NOTEWORTHY Previous findings have suggested that aging-related impairment in skeletal muscle reactive hyperemia is majorly influenced by a lower degree of tissue desaturation during ischemia in older individuals compared with young individuals. In a retrospective analysis including 83 tissue desaturation-matched individuals, we show that the degree of tissue desaturation is not a major determinant of aging-related impairments in reactive hyperemia.

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In recent years, there has been a notable surge in the popularity of beetroot-based dietary supplements, driven by their rich nitrate composition. Several types of beetroot-based dietary supplements can be found in markets worldwide; however, ensuring the safety of dietary supplements is a crucial consideration, as there is limited evidence on their safety, especially for older populations. Therefore, the purpose of the current study was to evaluate the safety and tolerability of a nitrate-rich beetroot extract in older participants taking supplements over 12 weeks. The participants were randomly assigned to receive 20 g daily of beetroot extract or a matching placebo. The safety and tolerability of the supplementation were evaluated as the occurrence of adverse events and anthropometric, biochemical, and hemodynamic parameters were measured. No serious adverse events were reported in any group. Anthropometric, biochemical, and hemodynamic parameter changes between the baseline and the end of the study were not statistically significant in either group. However, interestingly, the group receiving beetroot extract supplementation exhibited a notable increase in plasma nitrate levels (p = 0.076, f = 0.50) and showed a decrease in insulin levels (p = 0.026, f = 0.59). In conclusion, we found that 20 g of beetroot extract supplementation for 12 weeks was safe and well tolerated in older participants.

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Physical activities that are unaccustomed and involve eccentric muscle contractions have been demonstrated to temporarily impair macrovascular and microvascular functions, which may be caused by exercise-induced oxidative stress. Jaboticaba (Myrciaria jaboticaba) is a famous Brazilian berry that has been described to exhibit high antioxidant activity. However, no human study has investigated the protective effects of jaboticaba consumption against the vascular damage induced by eccentric exercise. Therefore, the present study aimed to assess whether supplementation with jaboticaba berry juice could positively affect macro- and microvascular functions within 48 hours after eccentric exercise. This randomized, double-blind, placebo-controlled, parallel trial enrolled 24 healthy participants consuming 250 mL per day of jaboticaba berry juice (containing ∼1,300 mg of total polyphenols) or placebo for 6 days. At the baseline, pre-exercise, and 24 h and 48 h postexercise stages, blood samples were taken for analysis of reduced glutathione (GSH) levels. Also, brachial artery flow-mediated dilation (FMD), blood flow, and tissue oxygen saturation (StO2) responses to 5-minute cuff occlusion were assessed using Doppler ultrasound and near-infrared spectroscopy, respectively. Our findings revealed significant decreases in blood GSH (P < 0.001, ES = 0.76), FMD (P = 0.005, ES = 0.48), reperfusion slope of StO2 (P = 0.018, ES = 0.42) at 24 h and blood flow (P = 0.012, ES = 0.42) at 48 h following eccentric exercise in the control group as compared to the jaboticaba berry juice group. Our results demonstrated that jaboticaba berry juice prevented the exercise-induced increase in reactive oxygen species production and protected macro- and microvascular functions against the damage caused by eccentric exercise, suggesting that jaboticaba berry consumption could protect the vascular function under conditions of imbalance in redox homeostasis.

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INTRODUCTION: Low cardiorespiratory fitness (CRF) increases the risk of cardiovascular disease by up to eightfold and is one of the strongest predictors of mortality. Some studies demonstrate impaired CRF in people living with type 1 and type 2 diabetes compared with those without diabetes, whereas others demonstrate no diabetes-associated impairment in CRF. PURPOSE: We aimed to determine whether diabetes can influence CRF and, if so, identify clinical associations underlying diabetes-associated exercise impairments. METHODS: Sixty-eight studies were included in the quantitative analysis. Standardized mean difference (SMD) was calculated and meta-analyses and meta-regressions were performed by using a random-effects model. RESULTS: Diabetes is associated with a large negative effect on CRF (SMD = -0.80, P < 0.001)-an effect that is partially mitigated, but still significant, in those with high physical activity levels (SMD = -0.50, P = 0.007). A sedentary lifestyle (SMD = -0.83, P = 0.007) and the presence of clinical complications related to diabetes (SMD = -1.66, P < 0.001) predict a greater magnitude of CRF reduction in people with diabetes compared with controls without diabetes. Both type 1 diabetes and type 2 diabetes are independently associated with impaired CRF compared with controls without diabetes; however, the effect is significantly greater in those type 2 diabetes (SMD = -0.97, P < 0.001). Meta-regression analysis demonstrates the effects of diabetes on CRF are primarily associated with HbA1c levels for type 1 diabetes ( B = -0.07, P < 0.001) and body mass index for type 2 diabetes ( B = -0.17, P = 0.005). CONCLUSIONS: These data demonstrate a negative influence of diabetes on the key risk factor of low CRF and provide critical insight into specific clinical markers of low CRF associated with diabetes.

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Endothelial dysfunction is commonly associated with a cardiovascular event, such as myocardial infarction. Myocardial infarction is marked by an ischemia/reperfusion (IR) phenomenon associated with endothelial dysfunction, contributing even more to future cardiovascular events. Although the supplementation with L-citrulline and nitrate from watermelon and beetroot have been used to improve vascular function, the effect of microencapsulated watermelon rind (WR) or its co-ingestion with beetroot (WR + B) on endothelial IR injury has not been addressed. Therefore, this study aimed to investigate the effect of a single dose of WR and WR + B on IR-induced macro-and microvascular dysfunction. In a randomized, crossover, placebo-controlled study, 12 volunteers underwent macro (flow-mediated dilation) and microvascular (muscle oxygen saturation) assessment and blood collection (to measure L-citrulline, L-arginine, nitrate and nitrite) before and after 20 min of blood occlusion in WR, WR + B and placebo conditions. Prolonged ischemia induced endothelial dysfunction in the macro but not in the microvasculature. The WR and WR + B supplementation significantly restored FMD after IR injury compared to the placebo (p < 0.05). However, there was no significant difference between WR and WR + B in the macrovascular function (p > 0.05). Plasma L-citrulline, L-arginine, nitrate, and nitrite significantly increased (p > 0.05) after WR and WR + B supplementation compared to the placebo. A single dose of WR and WR + B effectively minimizes IR-induced macrovascular endothelial dysfunction in healthy individuals. Beetroot co-ingestion with watermelon did not provide an additional effect of endothelial dysfunction induced by IR (NCT04781595, March 4, 2021).

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Cardiometabolic risk triggers a state of chronic and subclinical inflammation, conferring a higher risk of morbidity and mortality. Thus, minimal processing of foods with high nutritional value, in the form of flour, becomes an effective dietary strategy in preventing and treating cardiometabolic risk factors. This systematic review aims to evaluate the evidence on the effect of flour-based food intake on reducing the most common cardiometabolic risk factors. We included all randomized controlled trials published up to April 2023 in the main databases PubMed, Scopus and Web of Science. Eleven clinical trials were included. The amount of flour used in the studies ranged from 1.5 g to 36 g/day, and the supplementation period ranged from six weeks to 120 days. Green jackfruit flour, green banana flour, soy flour, flour from rind of the yellow passion fruit, and fenugreek powder demonstrated significant results in improve parameters of glucose homeostasis. Chia flour, green banana flour, soy flour, and fenugreek powder showed improvements in blood pressure measurements. Brazil nut flour and chia flour reduced total cholesterol. Chia flour also increased HDL cholesterol levels. The evidence presented in the current systematic review indicates that flour-derived foods intake is related to improve cardiometabolic risk factors parameters.

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In the present study, it was evaluated whether microencapsulated cocoa supplementation could attenuate endothelial dysfunction caused by eccentric exercise in healthy subjects. Thirteen volunteers were enrolled in this double-blind, placebo-controlled, crossover study. Flow-mediated dilatation (FMD), blood flow and muscle O2 saturation (StO2) were evaluated by ultrasound and near-infrared spectroscopy (NIRS), respectively, before and after microencapsulated cocoa supplementation. The eccentric exercise was performed after microencapsulated cocoa supplementation to generate vascular dysfunction. Eccentric exercise significantly reduced FMD in the PLA condition, but cocoa attenuated this exercise effect. No significant effect was observed on muscle StO2 and blood flow after eccentric exercise and nutritional supplementation. In conclusion, the present study showed that a single dose of microencapsulated cocoa ingestion attenuated FMD-induced eccentric exercise. These findings suggest that a single dose of microencapsulated cocoa may be an alternative nutritional strategy to attenuate vascular dysfunction induced by eccentric exercise in healthy individuals.

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Flow-mediated dilation (FMD) and muscle oxygen saturation (StO2) are measurements utilized to assess macro- and microvascular function, respectively. Macro- and microvascular dysfunction may occur differently depending on the clinical condition. Since microvascular responsiveness can influence upstream conduit artery hemodynamics, the present study aimed to investigate whether a correlation between FMD and muscle StO2 parameters exists. Sixteen healthy, young individuals were enrolled in this study. Femoral artery FMD and tibial anterior muscle StO2 were evaluated by ultrasound and near-infrared spectroscopy, respectively. The FMD and muscle StO2 parameters were assessed by employing a vascular occlusion test (VOT). The oxygen resaturation rate was determined by calculating the upslope of StO2 immediately after occlusion and the magnitude of reperfusion as the difference between the highest and lowest StO2 value achieved during the reperfusion phase. The oxygen desaturation rate and the magnitude of desaturation during the VOT were also evaluated. A significant correlation between the FMD and oxygen resaturation rate (r = 0.628; p = 0.009), magnitude of reperfusion (r = 0.568; p = 0.022), oxygen desaturation rate (r = -0.509; p = 0.044), and magnitude of desaturation (r = 0.644; p = 0.007) was observed. This study demonstrated a moderate association between the femoral artery FMD and tibial anterior StO2 parameters in young individuals.

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BACKGROUND/OBJECTIVES: Watermelon rind (usually discarded by consumers) presents a high L-citrulline content. Given that Lcitrulline is involved in nitric oxide (NO) synthesis, a crucial molecule that regulates vascular function, this study aimed to evaluate the effect of microencapsulated watermelon rind (MWR) on endothelial function and tissue oxygen saturation (StO2) assessed by flow-mediated dilation (FMD) and near-infrared spectroscopy, respectively. Plasma L-arginine and L-citrulline were also evaluated. SUBJECT/METHODS: Eleven participants ingested 30 g of MWR (containing 4 g of L-citrulline) and a placebo. Before and 30, 60, 90, and 120 min after ingestion, StO2 parameters were assessed, whereas FMD and plasma amino acids were analyzed 60 and 120 min after ingestion. RESULTS: The FMD improved 60 min after MWR without changes in StO2 parameters. Absolute plasma L-citrulline and relative change from baseline in plasma L-arginine increased 60 min after MWR ingestion. CONCLUSION: A single dose of microencapsulated watermelon rind containing 4 g of L-citrulline seems adequate to improve FMD response, but not StO2 parameters in healthy adults. (NCT04781595).

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Polyphenols-rich food has been utilized to induce a positive effect on human health. Considering that fruit and vegetable by-products (seeds, pomace, and peels) are sources of polyphenols, previous studies have investigated the effect of dietary supplementation with food by-products on cardiometabolic disorders, such as high fasting blood glucose, dyslipidemia, and obesity. Endothelial dysfunction has also been considered a cardiometabolic parameter, given that it precedes cardiovascular disease. However, there is a scarcity of narrative reviews reporting the effect of food by-product supplementation on cardiometabolic disorders in animal and human clinical trials. In this sense, the present narrative review aims to investigate the impact of fruit and vegetable by-product supplementation on cardiometabolic disorders in humans and animals, exploring the possible mechanisms whenever possible. Research articles were retrieved based on a search of the following databases: PubMed, ScienceDirect, and Google Scholar using the following keywords and synonyms combined: ("fruit by-products" or "food waste" or "pomace" or "bagasse" or "seeds" or "waste products") AND ("heart disease risk factors" or "endothelial dysfunction" or "atherosclerosis"). It was shown that fruit and vegetable by-products could efficiently improve cardiometabolic disorders in patients with chronic diseases, including hypertension, type II diabetes mellitus, and dyslipidemia. Such effects can be induced by the polyphenols present in food by-products. In conclusion, food by-product supplementation has a positive effect on cardiometabolic disorders. However, further studies investigating the effect of food by-products on cardiometabolic disorders in humans are still necessary so that solid conclusions can be drawn.

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Previous studies have investigated the impact of dietary nitrate on vascular function due to the association between dietary nitrate ingestion and improvement in nitric oxide (NO) bioavailability. Considering that NO can present different effects through vascular beds (macro- vs. microvasculature) due to the specific characteristic (function and morphology) that each vessel exhibits, it is crucial to investigate the effect of dietary nitrate ingestion on the macro- and microvascular function to understand the effect of nitrate on vascular function. For this reason, this review aimed to evaluate the impact of dietary nitrate on macro- and microvascular function in humans. A total of 29 studies were included in the systematic review, of which 19 studies evaluated the effect of nitrate supplementation on macrovascular function, eight studies evaluated the effect on microvascular function, and two studies evaluated the impact on both macro- and microvascular function. The literature suggests that dietary nitrate ingestion seems to improve the vascular function in macrovasculature, whereas microvascular function appears to be modest. Future studies investigating the effect of nitrate ingestion on vascular function should focus on measuring macro- and microvascular function whenever possible so that the impact of nitrate-rich foods on vascular segments could be better understood.

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The amino acid L-arginine is crucial for nitric oxide (NO) synthesis, an important molecule regulating vascular tone. Considering that vascular dysfunction precedes cardiovascular disease, supplementation with precursors of NO synthesis (e.g., L-arginine) is warranted. However, supplementation of L-citrulline is recommended instead of L-arginine since most L-arginine is catabolized during its course to the endothelium. Given that L-citrulline, found mainly in watermelon, can be converted to L-arginine, watermelon supplementation seems to be effective in increasing plasma L-arginine and improving vascular function. Nonetheless, there are divergent findings when investigating the effect of watermelon supplementation on vascular function, which may be explained by the L-citrulline dose in watermelon products. In some instances, offering a sufficient amount of L-citrulline can be impaired by the greater volume (>700 mL) of watermelon needed to reach a proper dose of L-citrulline. Thus, food technology can be applied to reduce the watermelon volume and make supplementation more convenient. Therefore, this narrative review aims to discuss the current evidence showing the effects of watermelon ingestion on vascular health parameters, exploring the critical relevance of food technology for acceptable L-citrulline content in these products. Watermelon-derived L-citrulline appears as a supplementation that can improve vascular function, including arterial stiffness and blood pressure. Applying food technologies to concentrate bioactive compounds in a reduced volume is warranted so that its ingestion can be more convenient, improving the adherence of those who want to ingest watermelon products daily.

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A biomass amino silica-functionalized material was successfully prepared by a simple sol-gel method. 3-Aminopropyltriethoxysilane (APTES) was added to a tannin-rich grape residue to improve its physicochemical properties and enhance the adsorption performance. The APTES functionalization led to significant changes in the material's characteristics. The functionalized material was efficiently applied in the removal of methyl orange (MO) due to its unique characteristics, such as an abundance of functional groups on its surface. The adsorption process suggests that the electrostatic interactions were the main acting mechanism of the MO dye removal, although other interactions can also take place. The functionalized biomass achieved a very high MO dye maximum adsorption capacity (Q max) of 361.8 mg g-1. The temperature positively affected the MO removal, and the thermodynamic studies indicated that the adsorption of MO onto APTES-functionalized biomass was spontaneous and endothermic, and enthalpy is driven in the physisorption mode. The regeneration performance revealed that the APTES-functionalized biomass material could be easily recycled and reused by maintaining very good performance even after five cycles. The adsorbent material was also employed to treat two simulated dye house effluents, which showed 48% removal. At last, the APTES biomass-based material may find significant applications as a multifunctional adsorbent and can be used further to separate pollutants from wastewater.

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PURPOSE: This study aimed to investigate the effects of AGE on microvascular reactivity, systolic blood pressure (SBP), and diastolic blood pressure (DBP) in older individuals at high risk for cardiovascular disease (CVD). Urinary thiosulfate was also investigated as an indirect marker of endogenous hydrogen sulfide (H2S) synthesis. The study was conducted in a randomized, double-blind, crossover, and placebo-controlled way. METHODS: Twenty-eight participants (14 male), 67 ± 6 years old with CVD risk factors, ingested 2.4 g of AGE or placebo (PLA). Near-infrared spectroscopy evaluated tissue oxygen saturation (StO2) during a vascular occlusion test (30 s baseline, 5 min occlusion, and 2 min reperfusion). The upslope of StO2 signal after cuff release was calculated to measure microvascular reactivity. Urinary thiosulfate levels were measured using a high-performance liquid chromatography system. RESULTS: The upslope of StO2 was significantly faster after AGE (1.01 ± 0.37% s-1) intake compared to PLA (0.83 ± 0.35% s-1; P < 0.001; d = 0.50). Relative changes in Δ% SBP from pre- to post-AGE intake (- 5.17 ± 5.77%) was significantly different compared to Δ% PLA (0.32 ± 5.99%; P = 0.001; d = 0.93). No significant changes in urinary thiosulfate concentrations were observed between interventions. Moreover, no significant gender effect in any parameter assessed was found. CONCLUSION: This study demonstrated that a single dose of AGE improved microvascular reactivity in older adults at risk of CVD despite such an effect was not linked with urinary thiosulfate levels. This trial was registered at clinicaltrials.gov as NCT04008693 (May 19, 2020).

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Ageing is associated with endothelial dysfunction and reduced cerebral blood flow and oxygenation. The present study aimed to investigate whether turmeric supplementation could improve cerebral oxygenation and blood volume during brain activation via dynamic handgrip exercise in older males and females. Twelve older males and females were studied using a double-blind, placebo-controlled, cross-over design. Participants ingested turmeric root extract or placebo. Heart rate and blood pressure were measured before and 2 hours after supplementation. Afterward, the exercise protocol was started, and cerebral oxygenation and blood volume were evaluated. During exercise, changes in cerebral oxygenation were higher after turmeric extract supplementation, as was blood volume compared to placebo. Changes in heart rate, systolic blood pressure, and diastolic blood pressure were not significant. The current findings indicate the potential for curcumin as an intervention for improving cerebral oxygenation and blood volume changes in older males and females. Clinical trial registry: NCT04119752.

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Dietary nitrate consumption from foods such as beetroot has been associated with many physiological benefits including improvements in vascular health and exercise performance. More recently, attention has been given to the use of dietary nitrate as a nutritional strategy to optimize muscular performance during resistance exercise. Our purpose was to perform a systematic review and meta-analysis of the research literature assessing the effect of dietary nitrate ingestion on muscular strength and muscular endurance. A structured search was carried out in accordance with PRISMA guidelines and from the total included studies (n = 34 studies), 12 studies had data for both measurement of strength and muscular endurance outcomes, 14 studies had data only for muscular strength outcome, and 8 studies had data only for muscular endurance outcome. Standardized mean difference (SMD) was calculated and meta-analyses were performed by using a random-effects model. Dietary nitrate ingestion was found to result in a trivial but significant effect on muscular strength (overall SMD = 0.08, P = 0.0240). Regarding muscular endurance dietary nitrate was found to promote a small but significant effect (overall SMD = 0.31, P < 0.0001). Dosage, frequency of ingestion, training level, muscle group, or type of contraction did not affect the findings, except for a greater improvement in muscle endurance during isometric and isotonic when compared to isokinetic contractions. Dietary nitrate seems to have a positive effect on muscular strength and muscular endurance, which is mostly unaffected by dosage, frequency of ingestion, training level, muscle group, or type of contraction. However, given the trivial to small effect, further experimental research on this topic is warranted.

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The aim the current study was to developed a watermelon rind powder (WRP), watermelon pulp powder (WPP), and beetroot powder (BP), in order to compare the stability of L-citrulline and nitrate with that of watermelon rind juice (WRJ), watermelon pulp juice (WPJ), and beetroot juice (BJ), respectively. The stability was evaluated during 32 days at 25, 4 and - 20 ºC. L-arginine and L-ornithine content were also evaluated. At day 0, a significantly higher L-citrulline and L-ornithine content in WRP was observed when compared to WPP. However, a significantly lower L-arginine content in WRP was observed when compared to WPP. L-citrulline content in WRP and WRJ was stable over 32 days in all temperatures evaluated, whereas it reduced in WPP in 32 days at 25 ºC and it is reduced in in WPJ in day 16 and day 32 at 25 °C. L-arginine content in WRP and WPP was stable over 32 days in all temperatures evaluated. A reduction was observed in WRJ at day 2, 4 and 32 at 25 °C and in WPJ at day 2, 4, 8, 16 and 32 days at 25 °C. L-ornithine content in WRP and WPP was stable over 32 days in all temperatures evaluated. An increase was observed in WRJ at day 2, 4 and 32 at 25 °C and in WPJ in day 2, 4, 8, 16 and 32 at 25 °C. Nitrate content in BP was stable over 32 days in all temperatures evaluated, while nitrate content in beetroot juice was reduced in day 2 at 25 °C and day 8 at 4 °C. In conclusion, L-citrulline of the microencapsulated watermelon rind and nitrate of the microencapsulated beetroot were stable throughout storage.

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KEY POINTS: The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2 -[H+ ] washout-induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin. Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation. We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia-induced hyperventilation in humans. Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion. Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2 -[H+ ] washout. ABSTRACT: The hypothetical mechanism for the increase in ventilation ( V̇E ) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO2 -[H+ ] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production/accumulation may increase the sensitivity to CO2 or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX-evoked increase in V̇E , 10 healthy men (24 ± 4 years) underwent 10 min trials of HX under saline and ascorbic acid infusion. V̇E , arterial and right internal right jugular vein (ijv) partial pressure for oxygen (PO2 ) and CO2 (PCO2 ), pH, oxidant (8-isoprostane) and antioxidant (ascorbic acid) markers, as well as cerebral blood flow (CBF) (Duplex ultrasonography), were quantified at each hyperoxic trial. HX evoked an increase in arterial partial pressure for oxygen, followed by a hyperventilatory response, a reduction in CBF, an increase in arterial 8-isoprostane, and unchanged PijvCO2 and ijv pH. Intravenous ascorbic acid infusion augmented the arterial antioxidant marker, blunted the increase in arterial 8-isoprostane and attenuated both the reduction in CBF and the HX-induced hyperventilation. Although ascorbic acid infusion resulted in a slight increase in PijvCO2 and a substantial decrease in ijv pH, when compared with the saline bout, HX evoked a similar reduction and a paired increase in the trans-cerebral exchanges for PCO2 and pH, respectively. These findings indicate that the poikilocapnic hyperoxic hyperventilation is likely mediated via the interaction of the acidic brain interstitial fluid and an increase in central chemoreceptor sensitivity to CO2 , which, in turn, seems to be evoked by the excessive ROS production/accumulation.

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BACKGROUND: There is a spectrum of possibilities for analyzing muscle O2 resaturation parameters for measurement of reactive hyperemia in microvasculature. However, there is no consensus with respect to the responsiveness of these O2 resaturation parameters for assessing reactive hyperemia. OBJECTIVES: This study investigates the responsiveness of the most utilized muscle O2 resaturation parameters to assess reactive hyperemia in the microvasculature of a clinical group known to exhibit impairments of tissue O2 saturation (StO2). METHODS: Twenty-three healthy young adults, twenty-nine healthy older adults, and thirty-five older adults at risk of cardiovascular disease (CVD) were recruited. Near-infrared spectroscopy (NIRS) was used to assess StO2 after a 5-min arterial occlusion challenge and the following parameters were analyzed: StO2slope_10s, StO2slope_30s, and StO2slope_until_baseline (upslope of StO2 over 10s and 30s and until StO2 reaches the baseline value); time to StO2baseline and time to StO2max (time taken for StO2 to reach baseline and peak values, respectively); ∆StO2reperfusion (the difference between minimum and maximum StO2 values); total area under the curve (StO2AUCt); and AUC above the baseline value (StO2AUC_above_base). RESULTS: Only StO2slope_10s was significantly slower in older adults at risk for CVD compared to healthy young individuals (p < 0.001) and to healthy older adults (p < 0.001). Conversely, time to StO2max was significantly longer in healthy young individuals than in older adult at CVD risk. CONCLUSIONS: Our findings suggest that StO2slope_10s may be a measure of reactive hyperemia, which provides clinical insight into microvascular function assessment.

CONTEXTO: Existe um espectro de possibilidades na análise dos parâmetros de ressaturação de O2 muscular como uma medida de hiperemia reativa na microvasculatura. No entanto, não há consenso com relação à responsividade desses parâmetros de ressaturação de O2 para avaliação de hiperemia reativa. OBJETIVOS: Este estudo investigou a capacidade de resposta dos parâmetros de ressaturação muscular de O2 mais utilizados para avaliar a hiperemia reativa na microvasculatura de um grupo clínico conhecido por apresentar comprometimento da saturação de O2 (StO2). MÉTODOS: Foram recrutados 23 jovens saudáveis, 29 idosos saudáveis e 35 idosos com risco para doença cardiovascular. A espectroscopia no infravermelho próximo foi usada para avaliar a StO2 após um teste de oclusão arterial de 5 minutos, no qual os seguintes parâmetros foram analisados: StO2slope_10s, StO2slope_30s e StO2slope_until_baseline (inclinação da StO2 em 10 s, 30 s e até StO2 atingir valores basais); tempo para StO2baseline e tempo para StO2máx (o tempo necessário para StO2 atingir os valores da linha de base e o máximo, respectivamente); ∆StO2reperfusão (a diferença entre o valor de StO2mínimo e StO2máximo); área total sob a curva (StO2AUCt); e área sob a curva acima do valor da linha de base (StO2AUC_above_base). RESULTADOS: Apenas StO2slope_10s foi significativamente mais lento em idosos em risco de doença cardiovascular comparados com indivíduos jovens saudáveis (p < 0,001) e idosos saudáveis (p < 0,001). Por outro lado, o tempo para StO2max foi significativamente maior em indivíduos jovens saudáveis do que em idosos em risco de doença cardiovascular. CONCLUSÕES: Nossos achados sugerem que StO2slope_10s pode ser uma medida de hiperemia reativa, que fornece informações clínicas sobre a avaliação da função microvascular.