Search

Alarmins are classified by their release from damaged or ruptured cells. Many alarmins have been found to increase vascular tone and oppose endothelium-dependent dilatation (EDD). Interleukin (IL)-33 plays a prominent role in lung injury and can be released during vascular injury and in chronic studies found to be cardioprotective. Our recent work has implicated IL-33 in acute vascular dysfunction following inhalation of engineered nanomaterials (ENM). However, the mechanisms linking IL-33 to vascular tone have not been interrogated. We therefore aimed to determine whether IL-33 directly influenced microvascular tone and endothelial function. Isolated feed arteries and in vivo arterioles from male and female Sprague-Dawley rats were used to determine direct vascular actions of IL-33. Mesenteric feed arteries and arterioles demonstrated reduced intraluminal diameters when treated with increasing concentrations of recombinant IL-33. IL-33 activated extracellular signal regulated kinase (ERK)1/2 of rat aortic smooth muscle cells but not phosphorylation of myosin light chain kinase. This suggested IL-33 may sensitize arterioles to Ca 2+ -mediated responses. Indeed, IL-33 augmented the myogenic- and phenylephrine-induced vasoconstriction. Additionally, incubation of arterioles with 1 ng IL-33 attenuated ACh-mediated EDD. Mechanistically, in human aortic endothelial cells, we demonstrate that IL-33-mediated ERK1/2 activation leads to inhibitory phosphorylation of serine 602 on endothelial nitric oxide synthase. Finally, we demonstrate that IL-33-ERK1/2 contributes to vascular tone following two known inducers of IL-33; ENM inhalation and the rupture endothelial cells. The present study provides novel evidence that IL-33 increases vascular tone via canonical ERK1/2 activation in microvascular smooth muscle and endothelium. Altogether, it is suggested IL-33 plays a critical role in microvascular homeostasis following barrier cell injury. KEY POINTS: Interleukin (IL)-33 causes a concentration-dependent reduction in feed artery diameter. IL-33 acts on vascular smooth muscle cells to augment Ca 2+ -mediated processes. IL-33 causes inhibitory phosphorylation of endothelial nitric oxide synthase and opposes endothelium-dependent dilatation. Engineered nanomaterial-induced lung injury and endothelial cell rupture in part act through IL-33 to mediate increased vascular tone., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Breakfast skipping has been suggested to be associated with cardiovascular diseases. However, whether breakfast skipping affects vascular endothelial function (VEF), a marker of cardiovascular diseases, remains unclear. This study aimed to investigate the impact of breakfast consumption (Eating trial) and skipping (Skipping trial) on brachial artery (BA) VEF in healthy breakfast eaters. A total of nine healthy individuals (4 females and 5 males) either had breakfast between 830 and 900 or skipped it and had lunch between 1200 and 1230, followed by a 3-h rest period until 1530. For BA VEF evaluation, flow-mediated dilation (FMD) was measured by ultrasound before and after breakfast and lunch. FMD was calculated as the percent change in BA diameter normalized to the shear rate area under the curve (FMD/SR AUC ). Blood glucose, plasma insulin, and plasma free fatty acid levels in capillaries were measured before and after breakfast and lunch. At 1530, the Eating trial, but not the Skipping trial, significantly increased FMD/SR AUC from baseline ( P = 0.006). The Skipping trial showed significantly lower changes in FMD/SR AUC from 830 than the Eating trial at 1530 ( P < 0.001). We found a significant inverse correlation between changes in FMD/SR AUC between 830 and 1530 and peak glucose levels after lunch ( r = -0.882, P < 0.001) and with an incremental area under the curve for glucose between 830 and 1530 ( r = -0.668, P < 0.001). These results suggest that a single bout of breakfast skipping can suppress BA VEF in the afternoon because of postlunch hyperglycemia. NEW & NOTEWORTHY Skipping breakfast does not affect vascular endothelial function (VEF) before lunch. However, after lunch on normal meals (i.e., not oral glucose tolerance test), VEF was found to be lower in those who skipped breakfast than those who ate breakfast. Such reduced postlunch VEF after skipping breakfast was associated with postprandial hyperglycemia. These results provide important insight into the impact of eating breakfast on VEF and glycemic control in healthy adults.

Background: Obesity (OB) is highly prevalent in females after menopause, especially visceral adipose tissue (VAT) accumulation which contributes to endothelial dysfunction. The endothelium assists in regulating blood flow (BF) during exercise and is attenuated in females with OB. The purpose of this study was to examine upper and lower limb flow-mediated dilation (FMD) and BF regulation during graded low-intensity submaximal exercises in postmenopausal females with BMI in the lean (LN), overweight (OW) and OB categories., Methods: Participants were grouped by body mass index (BMI) into LN (BMI 18.5-24.9 kg/m 2 ; n = 11), OW (BMI 25.0-29.9 kg/m 2 ; n = 15), and OB (BMI 30.0-39.9 kg/m 2 ; n = 13). FMD of the brachial (BA-FMD) and superficial femoral arteries (FA-FMD) were assessed. Subsequently, BF and vascular conductance (VC) in the upper (BA-BF and BA-VC) and lower limbs (FA-BF and FA-VC) were measured during separate 3-stage incremental rhythmic handgrip and plantarflexion exercises., Results: Significantly lower FA-FMD (P < 0.05) were seen in OB than LN and OW groups with no differences in BA-FMD. Increases in FA-BF and FA-VC were attenuated during the last stage of plantarflexion exercise at 30% of 1RM in OB (both P < 0.001) compared to LN and OW, while upper-body exercise vasodilation was unchanged. FA-BF and FA-VC during plantarflexion exercise were correlated to FA-FMD (FA-BF: r = 0.423, P = 0.007, FA-VC: r = 0.367, P = 0.021) and BMI (FA-BF: r = -0.386, P = 0.015, FA-VC: r = -0.456, P = 0.004)., Conclusion: Postmenopausal females with OB have reduced lower-limb endothelial and exercise vasodilator function during submaximal dynamic plantarflexion exercise compared to LN and OW. Our findings indicate that obesity may predict diminished leg endothelial function, BF and VC during exercise in postmenopausal females., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Endothelial dysfunction is an early predictor of atherosclerosis and cardiovascular disease. Flow-mediated dilation (FMD) is the gold standard to assess endothelial function in humans. FMD reproducibility has been mainly assessed in the brachial artery (BA) with limited research in lower limb arteries. The purpose of this study was to compare FMD reproducibility in the upper limb BA and lower limb superficial femoral artery (SFA) in young healthy adults.Fifteen young healthy adults (nine males; six females) underwent FMD, resting diameter, velocity, and shear rate measurements on three occasions to determine intra-and inter-day reproducibility in both BA and SFA, assessed by coefficient of variation (CV), intraclass correlation coefficient (ICC), and Bland-Altman plots.BA FMD CVs (intra-day: 4.2%; inter-day: 8.7%) and ICCs (intra-day: 0.967; inter-day: 0.903) indicated excellent reproducibility and reliability, while for SFA FMD, both CVs (intra-day: 11.6%; inter-day: 26.7%) and ICCs (intra-day: 0.898; inter-day: 0.651) showed good/moderate reproducibility and reliability. BA FMD was significantly more reproducible than SFA FMD (p < 0.05). Diameter reproducibility was excellent and similar between arteries, while resting velocity and shear rate have lower reproducibility in the BA compared to SFA. Bland-Altman plots displayed no proportional and fixed bias between measurements.In summary, SFA FMD is less reproducible than BA FMD, with identical volume of ultrasound training. Given the increasing interest in using SFA FMD to test the efficacy of interventions targeting lower limb's vascular health and as a potential biomarker for peripheral arterial disease risk, future studies should ensure higher levels of training for adequate reproducibility., (© 2024. The Author(s).)

There is no study that has investigated the impact of exercise in a combined hypoxic and hot environment on endothelial function. Therefore, we tested whether aerobic exercise in a combined hypoxic and hot conditions induces further enhancement of endothelial function. Twelve healthy males cycled at a constant workload (50% of their maximal oxygen uptake under normoxic/thermoneutral conditions) for 30 min in four different environments: exercise under normoxic condition (NOR: fraction of inspiratory oxygen or FiO 2  = 20.9%, 20°C), exercise under hypoxic condition (HYP: FiO 2  = 14.5%, 20°C), exercise under hot condition (HOT: FiO 2  = 20.9%, 30°C), and exercise under combined hypoxia and hot conditions (HH: FiO 2  = 14.5%, 30°C). Before, during, and after exercise, cardiovascular variables (e.g., heart rate, blood flow, and shear rate), blood variables, and endothelial function evaluated by flow-mediated dilation (FMD) were assessed. Heart rates were significantly higher throughout the HH trial's experimental period than the other trials (p < 0.05). However, in the HH trial, brachial artery blood flow and shear rate did not differ from those in other trials after exercise. Plasma catecholamines (epinephrine, norepinephrine, and dopamine) elevations in response to exercise were significantly higher in the HH trial than in the other three trials (p < 0.05). No considerable differences were observed in FMD responses among trials before and after the exercise. In conclusion, aerobic exercise in a combined hot and hypoxic environment further activated sympathetic nervous activity but did not considerably enhance blood flow, shear rate, or endothelial function., (© 2024 The Author(s). Clinical Physiology and Functional Imaging published by John Wiley & Sons Ltd on behalf of Scandinavian Society of Clinical Physiology and Nuclear Medicine.)

Mammalian and reptilian vascular tissues present basal release of 6-nitrodopamine, which is reduced when the tissues are pre-incubated with the NO synthase inhibitor L-N G -Nitro arginine methyl ester (L-NAME), or when the endothelium is mechanically removed. 6-Nitrodopamine induces vasorelaxation in pre-contracted vascular rings by antagonizing the dopaminergic D 2-like receptor. Here it was investigated whether male swine vessels (including carotid, left descendent coronary, renal, and femoral arteries) release 6-nitrodopamine, dopamine, noradrenaline, and adrenaline, as measured by liquid chromatography coupled to tandem mass spectrometry. The in vitro vasorelaxant action of 6-nitrodopamine was evaluated in carotid, coronary, renal, and femoral arteries precontracted by U-46619 (3 nM), and compared to that induced by the dopamine D 2 -receptor antagonist L-741,626. Expression of tyrosine hydroxylase and the neuromaker calretinin was investigated by immunohistochemistry. All vascular tissues presented basal release of endothelium-derived catecholamines. The relaxation induced by 6-nitrodopamine was not affected by preincubation of the tissues with either L-NAME (100 μM, 30-min preincubation) or the heme-site inhibitor of soluble guanylyl cyclase ODQ (100 μM, 30-min preincubation). Electrical field stimulation (EFS)-induced contractions were significantly potentiated by previous incubation with L-NAME, but unaffected by ODQ preincubation. The contractions induced by EFS were reduced by preincubation with either 6-nitrodopamine or L-741,626. Immunohistochemistry in all arteries revealed the presence of tyrosine hydroxylase in the endothelium, whereas immunoreactivity for calretinin was negative. Swine vessels present basal release of endothelium-derived catecholamines and expression of tyrosine hydroxylase in the endothelium. The vasodilation induced by 6-nitrodopamine is due to blockade of dopaminergic D 2 -like receptors., Competing Interests: Declaration of competing interest The authors declare no competing or financial interests., (Copyright © 2024. Published by Elsevier Inc.)

Ischaemic preconditioning (IPC), brief periods of ischaemia immediately followed by reperfusion applied to a vascular bed, has emerged as a method to improve exercise performance. There is, however, a lack of research exploring repeated episodes of IPC on anaerobic performance. The aim of this study was to determine if a 2-week repeated IPC intervention could enhance anaerobic performance in male academy football players. Eight male academy football players completed two, 2-week intervention trials: six IPC episodes (4 × 5 min at 220 mmHg per episode), and six SHAM episodes (4 × 5 min at 20 mmHg per episode). Prior to and following each intervention trial, the participants completed assessments of anaerobic performance (Running Anaerobic Sprint Test [RAST]), and superficial femoral artery endothelial function (flow-mediated dilation [FMD]). IPC significantly enhanced peak and mean power output by 12% ( p  = 0.026) and 11% ( p  = 0.019) and significantly improved superficial femoral artery FMD ( p  = 0.049). The increase in endothelial function suggests that this may be a mechanism contributing to this enhancement of anaerobic performance. The present study supports the use of repeated IPC prior to matches and training sessions to enhance anaerobic performance.

Objective: To assess the changes in blood vessel stiffness and digital pulse wave amplitude because of flowmediated dilatation, and to explore how these two variables change when endothelial dysfunction is experimentally induced., Methods: The experimental study was conducted at the departments of physiology at the College of Medicine, Mustansiriyah University, and the College of Medicine, Al-Iraqia University, Baghdad, Iraq, from October 14, 2021, to May 31, 2022, and comprised healthy young males who were subjected to the flow-mediated dilatation technique on the left brachial artery. Pulse transit time and the amplitude of the digital pulse wave were measured during reactive hyperaemia for 2.5 minutes from the left middle finger using a piezoelectric pressure sensor and a simultaneous Lead I electrocardiogram. Endothelial dysfunction (ED) was induced by oscillatory and retrograde shear rates. The correlation between variables was calculated in Excel running on the Windows operating system., Results: There were 10 second-year medical students with mean age 22±0 years and mean body mass index 25.7±4.8kg/m2. During reactive hyperaemia, pulse transit time was significantly increased by 3-5% in both normal endothelium and experimentally induced endothelial dysfunction relative to the pre-occluded artery, and the difference was not significant (p>0.05). Digital pulse wave amplitude increased significantly in normal endothelium relative to the pre-occluded artery (p<0.05), but not in experimentally-induced endothelial dysfunction (p>0.05)., Conclusions: The pulse transit time and digital pulse wave amplitudes of the photo plethysmography signal may be used to detect changes in vessel wall diameter and tone throughout the reactive hyperaemia process. Digital pulse wave amplitude was better able to detect experimentally-induced endothelial dysfunction, as assessed by the flowmediated dilatation protocol, than pulse transit time.

Sirtuin 3 has been shown to regulate endothelial function and coronary flow reserve in mice. Knockout of SIRT3 reduced endothelial nitric oxide synthase expression in the mouse hearts. In this study, we investigate whether endothelial SIRT3 regulates vascular function and myogenic responses in distal intramural branches of the left anterior descending coronary artery (CA) and middle cerebral artery (MCA) of mice. Both male and female endothelial SIRT3 knockout (SIRT3 EC KO) mice and control SIRT3 LoxP mice were used and CA and MCA were dissected and mounted in a myograph system. The myogenic response was evaluated by measuring changes in inner diameter in response to 20 mmHg stepwise increases in intraluminal pressure in PSS (active diameter) and Ca2 + -free PSS (passive diameter). Acetylcholine (Ach)-induced endothelial-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelial-independent relaxation (EIR) were examined. Our results showed that the myogenic responses were significantly impaired in both the CA and MCA of SIRT3 EC KO mice. Furthermore, female mice had worsened myogenic response in MCA. In CA, EDR was abolished in both male and female SIRT3 EC KO mice. Intriguingly, EIR was only reduced in the female mice. In MCA, EDR was reduced in male SIRT3 EC KO mice, whereas EIR was decreased in both male and female mice. Female SIRT3 EC KO mice had profound dysfunction in CA, whereas male mice exhibited more dysfunction in MCA. These data revealed a sex and organ-specific role of endothelial SIRT3 in vascular function and myogenic responses. Our study suggests that endothelial SIRT3 is necessary for maintaining vascular function and blood flow autoregulation., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: This study aimed to examine the effects of a six-week of concurrent training using high-intensity interval plus resistance training on flow-mediated dilation and pulse wave velocity in hypertensive, elevated blood pressure, or normotensive. A secondary goal was to analyze the inter-individual variability., Methods: A randomized controlled clinical trial was executed with 60 adult participants distributed across six groups: three control groups of hypertensive, elevated blood pressure, or normotensive and other three experimental hypertensive, elevated blood pressure, and normotensive groups, each comprising n=10 individuals. Participants underwent a six-week intervention of concurrent exercise using high-intensity interval plus resistance training three-weekly. Flow mediated dilation and pulse wave velocity and secondary vascular assessments were conducted before and after the intervention., Results: The hypertensive exercise group exhibited a significant increase in flow mediated dilation (Δ+7.7%; p=0.003) and a reduction in pulse wave velocity (Δ-1.2ms -1 ; p<0.0001). The normotensive exercise group also showed a significant increase in flow mediated dilation (Δ+8.4%, p=0.002)., Conclusion: The six-week concurrent exercise using high-intensity interval plus resistance training protocol, characterized by its clinical time-efficiency, was effective in improving endothelial function, as demonstrated by increased flow mediated dilation, and in reducing arterial stiffness, indicated by decreased pulse wave velocity., (Copyright © 2024 SEH-LELHA. Publicado por Elsevier España, S.L.U. All rights reserved.)

30 min of moderate-intensity aerobic exercise per day is recommended, but the response and adaptation of endothelial function (EF) to this exercise remains controversial. The purpose of this study was to determine the changes in EF in endurance trained and untrained individuals before and after this exercise and to compare the differences between trained and untrained individuals. Twelve endurance-trained male college athletes (trained group) and 12 untrained male college students (untrained group) performed a 30-min run at an intensity of 60% VO 2 max. Brachial artery flow-mediated dilation (FMD) was measured before exercise, 30 min and 60 min after exercise, and the following morning. Resting diameter and maximum diameter showed large time effects (p < 0.001, η 2  = 0.533; p < 0.001, η 2  = 0.502). Resting diameters at 30 and 60 min after exercise were higher than before exercise in both the untrained and trained groups (p < 0.05), and maximum diameters at 30 min after exercise were higher than before exercise in both the untrained and trained groups (p < 0.01). Resting diameter and maximum diameter also exhibited some group effects (p = 0.055, η 2  = 0.157; p = 0.041, η 2  = 0.176). Resting diameters and maximum diameters were higher in the trained group than in the untrained group before exercise (p < 0.05). FMD (%) showed no time, group, or time-group interaction effects. 30 min of moderate-intensity aerobic exercise can increase resting and maximal arterial diameters in both trained and untrained young men, but has no effect on FMD. Long-term endurance training has the potential to increase resting and maximal arterial diameters in young men, but not necessarily FMD., (© 2024. The Author(s).)

Measurement of flow-mediated vasodilation (FMD) in the brachial artery by using ultrasound is a well-established technique for evaluating endothelial function. To make the measurement quicker and simpler than the measurements of conventional ultrasound FMD (uFMD), we have developed a new noninvasive method, plethysmographic FMD (pFMD), to assess vascular response to reactive hyperemia in the brachial artery. The aim of this study was to determine the accuracy of measurement of pFMD in comparison to that of measurement of conventional uFMD. This study was a multi-center, cross-sectional study. We compared pFMD by a new device using cuff pressure and volume with conventional uFMD using ultrasound in 50 men (mean age, 41 ± 9 years). pFMD significantly correlated with conventional uFMD (β = 0.59, P < 0.001). In Bland-Altman plot analysis of pFMD and conventional uFMD, the mean difference of pFMD and conventional uFMD was 0.78%, and limits of agreement (mean difference ±2 standard deviations of the difference) ranged from -4.53% to 6.11%. We demonstrated validity of the new method for measurement of pFMD, which can automate the evaluation of endothelial function in a short time. Measurement of pFMD is simpler than measurement of conventional uFMD and may have reduced artificial bias compared to that of conventional uFMD measurement (URL for Clinical Trial: https://ethics.hiroshima-u.ac.jp/site/wp-content/uploads/2022/12/eki&#95;giji20221213.pdf . Registration Number for Clinical Trial: E2022-0131)., (© 2024. The Author(s).)

Habitual short sleep durations are associated with several cardiovascular diseases. Experimental research generally supports these findings as metrics of arterial function are impaired after complete deprivation of sleep and after longer periods of partial sleep restriction. The acute influence of a single instance of partial sleep restriction (PSR), however, has not been defined. We evaluated arterial structure and function among 32 university-aged participants on two occasions: once after normal habitual sleep (NS), and again the morning after an acute partial sleep restriction (PSR) intervention involving only 3 h of sleep for a single night. Endothelial function was measured using ultrasonography at the brachial artery via flow-mediated dilatation (FMD), and a ramp peak oxygen uptake test was used to evaluate cardiorespiratory fitness. Blood samples were collected from a subset of participants to investigate the influence of circulatory factors on cellular mechanisms implicated in endothelial function. Sleep duration was lower after a night of PSR compared to NS (P < 0.001); however, there were no appreciable differences in any haemodynamic outcome between conditions. FMD was not different between NS and PSR (NS: 6.5 ± 2.9%; PSR: 6.3 ± 2.9%; P = 0.668), and cardiorespiratory fitness did not moderate the haemodynamic response to PSR (all P > 0.05). Ex vivo cell culture results aligned with in vivo data, showing that acute PSR does not alter intracellular processes involved in endothelial function. No differences in arterial structure or function were observed between NS and acute PSR in healthy and young participants, and cardiorespiratory fitness does not modulate the arterial response to acute sleep restriction., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Purpose: Postmenopausal women experience augmented aortic hemodynamic responses to isometric handgrip (IHG) exercise and metaboreflex activation post-exercise muscle ischemia (PEMI). Relationships between endothelial function brachial artery flow-mediated dilation (FMD) and aortic stiffness carotid-femoral pulse wave velocity (cfPWV) with aortic pulsatile hemodynamics during IHG and PEMI have not been determined. The relationships between aortic hemodynamic responses to PEMI were evaluated., Methods: Aortic blood pressure (BP), wave reflection, and pressure of forward (Pf) and backward (Pb) waves were measured using arterial tonometry at rest, IHG at 30% maximal force, and PEMI in 30 (15/group) postmenopausal women with low (≤ 4.5%) and normal (≥ 5.5%) FMD. Hemodynamic responses were analyzed as the change (Δ) from rest to the last minute of IHG and PEMI., Results: Brachial and aortic systolic BP (SBP) responses to IHG were higher in the low vs normal FMD group (P < 0.05). Aortic SBP (Δ20 ± 8 vs Δ11 ± 7 mmHg), pulse pressure (PP) (Δ12 ± 8 vs Δ6 ± 4 mmHg), augmented pressure (AP) (Δ5 ± 3 vs Δ2 ± 2 mmHg), and Pb (Δ6 ± 4 vs Δ3 ± 2 mmHg) responses to PEMI were greater (P < 0.05) in women with low vs. normal FMD. FMD was negatively correlated with aortic SBP, PP, AP, and Pb (P < 0.05) responses to PEMI. cfPWV was not correlated with responses to PEMI., Conclusion: Endothelial dysfunction relates to augmented aortic pulsatile load during metaboreflex activation, which may increase cardiovascular risk in postmenopausal women., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Study Objectives: Against the current backdrop of population ageing, the correlation between cardiovascular diseases and endothelial dysfunction is increasingly important. Exercise, a simple and accessible method of preventing and ameliorating numerous diseases, has been demonstrated to significantly enhance endothelial function. This study aimed to assess the effects of aerobic exercise (AE), resistance exercise (RE), combined exercise (CE) and high-intensity interval training (HIIT) on vascular endothelial function in middle-aged and older adults. Flow-mediated dilation (FMD) is a non-invasive ultrasound technique used to measure endothelial function. Direct and indirect comparisons were used to determine which exercise modality most effectively improved vascular endothelial function in this demographic., Methods: This comprehensive systematic review and network meta-analysis examined randomised controlled trials (RCTs) comparing the effects of four different exercise interventions (AE, RE, CE and HIIT) to a control intervention on FMD in middle-aged and older adults., Results: The analysis included 20 RCTs involving 1,123 participants. The surface under the cumulative ranking curve (SUCRA) analysis indicated that AE was the most effective in improving FMD (SUCRA = 68.9 %), followed by HIIT (SUCRA = 62.5 %), RE (SUCRA = 58.8 %), CE (SUCRA = 54.9 %) and CON (SUCRA = 4.9 %)., Conclusions: This network meta-analysis of various interventions for FMD in middle-aged and older adults found that AE was the most effective in improving FMD (SUCRA = 68.9 %). These findings suggest that AE could be a valuable intervention in clinical practice for enhancing vascular health in this population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: The nadir pressure responses to cardiac cycles absent of muscle sympathetic nerve activity (MSNA) bursts (or non-bursts) are typically reported in studies quantifying sympathetic transduction, but the information gained by studying non-bursts is unclear. We tested the hypothesis that longer sequences of non-bursts (≥8 cardiac cycles) would be associated with a greater nadir diastolic blood pressure (DBP) and that better popliteal artery function would be associated with an augmented reduction in DBP., Methods: Resting beat-by-beat DBP (via finger photoplethysmography) and common peroneal nerve MSNA (via microneurography) were recorded in 39 healthy, adults (age 23.4 ± 5.3 years; 19 females). For each cardiac cycle absent of MSNA bursts, the mean nadir DBP (ΔDBP) during the 12 cardiac cycles following were determined, and separate analyses were conducted for ≥8 or < 8 cardiac cycle sequences. Popliteal artery endothelial-dependent (via flow-mediated dilation; FMD) and endothelial-independent vasodilation (via nitroglycerin-mediated dilation; NMD) were determined., Results: The nadir DBP responses to sequences ≥8 cardiac cycles were larger (-1.40 ± 1.27 mmHg) than sequences <8 (-0.38 ± 0.46 mmHg; p < 0.001). In adjusting for sex and burst frequency (14 ± 8 bursts/min), larger absolute or relative FMD (p < 0.01), but not NMD (p > 0.53) was associated with an augmented nadir DBP. This overall DBP-FMD relationship was similar in sequences ≥8 (p = 0.04-0.05), but not <8 (p > 0.72)., Conclusion: The DBP responses to non-bursts, particularly longer sequences, were inversely associated with popliteal endothelial function, but not vascular smooth muscle sensitivity. This study provides insight into the information gained by quantifying the DBP responses to cardiac cycles absent of MSNA., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Flow-mediated dilation (FMD) is a common measure of endothelial function and an indicator of vascular health. Automated software methods exist to improve the speed and accuracy of FMD analysis. Compared with commercial software, open-source software offers similar capabilities at a much lower cost while allowing for increased customization specific to users' needs. We introduced modifications to an existing open-source software, FloWave.us to better meet FMD analysis needs. The purpose of this study was to compare the repeatability and reliability of the modified FloWave.us software to the original software and to manual measurements. To assess these outcomes, duplex ultrasound imaging data from the popliteal artery in older adults were analyzed. The average percent FMD for the modified software was 6.98 ± 3.68% and 7.27 ± 3.81% for observer 1 and 2 respectively, compared with 9.17 ± 4.91% and 10.70 ± 4.47% with manual measurements and 5.07 ± 31.79% with the original software for observer 1 . The modified software and manual methods demonstrated higher intraobserver intraclass correlation coefficients (ICCs) for repeated measures for baseline diameter, peak diameter, and percent FMD compared with the original software. For percent FMD, the interobserver ICC was 0.593 for manual measurements and 0.723 for the modified software. With the modified method, an average of 97.7 ± 2.4% of FMD videos frames were read, compared with only 17.9 ± 15.0% frames read with the original method when analyzed by the same observer. Overall, this work further establishes open-source software as a robust and viable tool for FMD analysis and demonstrates improved reliability compared with the original software. NEW & NOTEWORTHY This study improves edge detection capabilities and implements noise reduction strategies to optimize an existing open-source software's suitability for flow-mediated dilation (FMD) analysis. The modified software improves the precision and reliability of FMD analysis compared with the original software algorithm. We demonstrate that this modified open-source software is a robust tool for FMD analysis.

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave-reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points-Baseline (BL), following 10, 20, 30 and 40 km, 1 h post-completion (1HP) and 24 h post-completion (24HP). Flow-mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Chronic exercise training is associated with an "athlete's artery" phenotype in young adults and an attenuated age-related decline in endothelium-dependent arterial function. Adolescence is associated with an influx of sex-specific hormones that may exert divergent effects on endothelial function, but whether training adaptations interact with biological maturation to produce a "youth athlete's artery" has not been explored. We investigated the influence of exercise-training status on endothelium-dependent arterial function during childhood and adolescence. Brachial artery flow-mediated dilation (FMD) was assessed in n = 102 exercise-trained (males, n = 25; females, n = 29) and untrained (males, n = 23; females, n = 25) youths, characterized as pre (males, n = 25; females, n = 26)- or post (males, n = 23; females, n = 28)-predicted age at peak height velocity (PHV). Baseline brachial artery diameter was larger in post- compared with pre-PHV youths ( P ≤ 0.001), males compared with females ( P ≤ 0.001), and trained compared with untrained youths (3.26 ± 0.51 vs. 3.11 ± 0.42 mm; P = 0.041). Brachial FMD was similar in pre- and post-PHV youths ( P = 0.298), and males and females ( P = 0.946). However, exercise-trained youths demonstrated higher FMD when compared with untrained counterparts (5.3 ± 3.3 vs. 3.0 ± 2.6%; P ≤ 0.001). Furthermore, brachial artery diameter ( r 2 = 0.142; P = 0.007 vs. r 2 = 0.004; P = 0.652) and FMD ( r 2 = 0.138; P = 0.008 vs. r 2 = 0.003; P = 0.706) were positively associated with cardiorespiratory fitness in post-, but not pre-PHV youths, respectively. Collectively, our data indicate that exercise training is associated with brachial artery remodeling and enhanced endothelial function during youth. However, arterial remodeling and endothelium-dependent function are only associated with elevated cardiorespiratory fitness during later stages of adolescence. NEW & NOTEWORTHY We report preliminary evidence of the "youth athlete's artery," characterized by training-related arterial remodeling and elevated endothelium-dependent arterial function in children and adolescents. However, training-related adaptations in brachial artery diameter and flow-mediated dilation (FMD) were associated with cardiorespiratory fitness in adolescents, but not in children. Our findings indicate that endothelium-dependent arterial function is modifiable with chronic exercise training during childhood, but the association between FMD and elevated cardiorespiratory fitness is only apparent during later stages of adolescence.

Purpose: Acute resistance exercise decreases endothelial function in sedentary individuals but not in strength-trained (ST) individuals. However, the underlying mechanism(s) of vascular protection in ST individuals remains unclear. Herein, we compared catecholamines, endothelin-1 (ET-1), and nitric oxide (NOx) releases after acute resistance exercise between sedentary and ST individuals., Methods: The untrained (UT) group comprised 12 male individuals with no regular training, while the ST group comprised 12 male individuals. Participants performed a session of resistance exercise, which consisted of 3 sets of 10 repetitions at 75% of one repetition maximum. Heart rate (HR) and blood pressure were measured during resistance exercise. Brachial artery flow-mediated dilation (FMD), blood pressure, HR, and blood collection were undertaken before and 10, 30, and 60 min after the resistance exercise., Results: No significant difference was found in baseline brachial artery FMD between the groups (P > 0.05). Brachial artery FMD was significantly reduced in the UT group (P < 0.05) but it was prevented in the ST group after the resistance exercise. Significant differences were found at 10, 30, and 60 min after the resistance exercise in brachial artery ΔFMD from baseline between groups (P < 0.05). Blood pressure, HR, plasma epinephrine, norepinephrine, dopamine, serum endothelin-1, and plasma NOx responses did not differ between groups throughout the experimental period., Conclusion: In conclusion, preserved endothelial function in response to acute resistance exercise in ST male individuals is independent of catecholamines, ET-1, and NOx responses., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aging is associated with vascular endothelial dysfunction observed through a progressive loss of flow-mediated dilation caused partly by a decreased nitric oxide bioavailability. Intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, was reported to either maintain or improve vascular function in young adults. The aim of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Twelve young adults and 11 older adults visited the laboratory on two occasions. Plasma nitrate concentrations and brachial artery flow-mediated dilation were assessed before and after exposure to either intermittent hypoxia or a sham protocol. Intermittent hypoxia consisted of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, and the sham protocol consisted of eight 4-min normoxic cycles interspersed with breathing room air. Vascular responses were assessed during intermittent hypoxia and the sham protocol. Intermittent hypoxia elicited a brachial artery vasodilation but did not change brachial artery shear rate in both young and older adults. Plasma nitrate concentrations were not significantly affected by intermittent hypoxia compared with the sham protocol in both groups. Brachial artery flow-mediated dilation was not acutely affected by intermittent hypoxia or the sham protocol in either young or older adults. In conclusion, the brachial artery vasodilatory response to intermittent hypoxia was not influenced by age. Intermittent hypoxia increased brachial artery diameter but did not acutely affect endothelium-dependent vasodilation in young or older adults. NEW & NOTEWORTHY The objective of this study was to determine the impact of age on the vascular response to intermittent hypoxia. Eight 4-min bouts of hypoxia at a targeted oxygen saturation of 80% induced a brachial artery vasodilation in both young and older adults, indicating that age does not influence the vasodilatory response to intermittent hypoxia. Intermittent hypoxia did not acutely affect brachial artery flow-mediated dilation in young or older adults.

Background and Purpose: The single layer of cells lining all blood vessels, the endothelium, is a sophisticated signal co-ordination centre that controls a wide range of vascular functions including the regulation of blood pressure and blood flow. To co-ordinate activities, communication among cells is required for tissue level responses to emerge. While a significant form of communication occurs by the propagation of signals between cells, the mechanism of propagation in the intact endothelium is unresolved., Experimental Approach: Precision signal generation and targeted cellular manipulation was used in conjunction with high spatiotemporal mesoscale Ca 2+ imaging in the endothelium of intact blood vessels., Key Results: Multiple mechanisms maintain communication so that Ca 2+ wave propagation occurs irrespective of the status of connectivity among cells. Between adjoining cells, regenerative IP 3 -induced IP 3 production transmits Ca 2+ signals and explains the propagated vasodilation that underlies the increased blood flow accompanying tissue activity. The inositide is itself sufficient to evoke regenerative phospholipase C-dependent Ca 2+ waves across coupled cells. None of gap junctions, Ca 2+ diffusion or the release of extracellular messengers is required to support this type of intercellular Ca 2+ signalling. In contrast, when discontinuities exist between cells, ATP released as a diffusible extracellular messenger transmits Ca 2+ signals across the discontinuity and drives propagated vasodilation., Conclusion and Implications: These results show that signalling switches underlie endothelial cell-to-cell signal transmission and reveal how communication is maintained in the face of endothelial damage. The findings provide a new framework for understanding wave propagation and cell signalling in the endothelium., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

This study investigated the impact of comprehensive sleep patterns on glycaemic parameters and endothelial function in adolescents and young adults with type 1 diabetes (T1D). Thirty subjects with type 1 diabetes (aged 13-25) without chronic complications participated. For 1 week, glucose levels were monitored by real-time continuous glucose monitoring (CGM) and sleep was simultaneously assessed by actigraphy. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Flow-mediated dilatation (FMD) measured endothelial function at the brachial artery. Insulin sensitivity was determined by calculated estimated glucose disposal rate (eGDR). Glycaemic control was assessed using haemoglobin A1C (HbA1C) levels. To address potential confounding by metabolic syndrome on the FMD results, three affected subjects were excluded from FMD correlation analyses. Participants with PSQI scores >5 had a lower %FMD compared with those with scores ≤5 (4.6 ± 3.7% vs. 7.6 ± 3.0%, p = 0.03). Multivariate analysis indicated that lower sleep efficiency and higher sleep duration variability were associated with higher HbA1C levels (β = -0.076, 95%CI [-0.145, -0.008], p = 0.029; β = 0.012, 95%CI [0.001, 0.023], p = 0.033). Irregular sleep timing and lower sleep efficiency were related to decreased insulin sensitivity (sleep midpoint irregularity β = -1.581, 95%CI [-2.661, -0.502], p = 0.004, and sleep efficiency β = 0.147, 95%CI [0.060, 0.235], p = 0.001). No significant associations were found between glycaemic parameters and FMD. Our study demonstrated that sleep irregularity in type 1 diabetes was associated with glycaemic control and insulin resistance, while poor subjective sleep quality was linked to endothelial dysfunction. Promoting healthy sleep habits, including consistent sleep timing could benefit metabolic and cardiovascular health in type 1 diabetes., (© 2023 European Sleep Research Society.)

The purpose of this study was to examine the effects of plant- versus animal-based food intake before exercise on arterial function and subsequent aerobic exercise capacity. Eleven healthy adult males (mean age, 22.6 ± 1.8 years) participated in this study. A plant- or animal-based randomized meal type crossover comparison was conducted on separate days with a uniform protein, fat, and carbohydrate balance. Both carotid-femoral pulse wave velocity (cfPWV), femoral-ankle pulse wave velocity (faPWV), and brachial artery flow-mediated dilatation (FMD) were measured as indexes of aortic and peripheral arterial stiffness and vascular endothelial function, respectively, before and at 120 min after the meal. After these measurements, maximal oxygen uptake was assessed using a graded power test on an electronically braked cycle ergometer. The results revealed that cfPWV was significantly lower, whereas FMD was significantly higher, at 120 min after compared with before the plant-based meal ( p  = 0.01 and 0.02, respectively). By contrast, cfPWV and FMD did not change at 120 min after compared with before the animal-based meal. In addition, faPWV did not change at 120 min after compared with before the meal for either meal type. Maximal oxygen uptake was higher in the plant- than in the animal-based meal type ( p  = 0.02). These results suggest that pre-exercise plant-based food intake may improve central arterial stiffness and vascular endothelial function, which may have favorable implications for aerobic exercise capacity., Competing Interests: The authors have no conflict of interest to declare.

Background: Endothelial function declines with age and plays a critical role in cardiovascular health. Therefore, investigating endothelial function in successful aging models, such as centenarians, is of interest. Flow-mediated dilation (FMD) of the brachial artery is the gold standard for measuring endothelial function in vivo in humans. Therefore, we investigated, for the first time, the FMD of the brachial artery in a group of healthy centenarians., Methods: Selected as part of the ABCD project (nutrition, cardiovascular wellness, and diabetes) centenarians (aged ≥100 years) living in the municipalities of Madonie (Palermo, Italy) were compared with a younger (aged <65 years) sex-matched control group from the ABCD general cohort. FMD of the brachial artery was measured in all participants using a real-time computed video analysis system for B-mode ultrasound images. Body composition (bioimpedance), carotid intima-media thickness (IMT), and ankle-brachial index (ABI) were also measured., Results: Eleven participants (males 36.4 %; age: 101 ± 1 years) out of 28 healthy centenarians successfully cooperated with the FMD test procedures, which require remaining with the upper limb immobile for approximately 10 min. This subgroup was compared with a control group of 76 healthy and younger individuals (males 36.8 %; aged: 41 ± 14 years; P < 0.001). Centenarians exhibited better endothelial function than the control group (FMD: 12.1 ± 4.3 vs 8.6 ± 5.3 %; P < 0.05). The carotid IMT was higher in the centenarian group than in the control group (0.89 ± 0.09 vs 0.56 ± 0.18 mm; P < 0.001), whereas the ABI was comparable between the two groups., Conclusions: This small group of centenarians demonstrated an unusually favorable endothelial function, which may contribute to their unique aging profile. Further research is needed to determine whether FMD is a valid prognostic marker for successful aging., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. Financial disclosure This research received no external funds., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Endothelial dysfunction is crucial factor to the hypertension occurrence, and controversy remains regarding the effect of exercise on improving endothelial function in hypertensive patients. The authors used meta-analysis to evaluate the intervention effect of exercise on endothelial function in hypertensive patients and to investigate exercise protocols that may have a greater intervention effect. A total of 37 studies and a total of 2801 participants were included. The results were as follows: endogenous nitric oxide (NO)[SMD = .89, 95% CI (.48, 1.30), p < .0001], endothelin-1 (ET-1): [SMD = -.94, 95% CI (-1.15, -.73), p <. 0001], flow-mediated dilation (FMD) [SMD = -.57, 95% CI (.36, .79), p < .000001]. In subgroup analysis, high-intensity aerobic exercise, with a single exercise duration of 35-50 min, 3-4 times/week for a total of 10-12 weeks, had the largest amount of intervention effect on NO, and moderate-intensity resistance exercise, with a single exercise duration of ≥60 min, 6 times/week for a total of 15-18 weeks, had the largest amount of intervention effect on ET-1. In conclusion, exercise can improve NO levels, FDM levels, and reduce ET-1 secretion of hypertension patients, thereby improve their endothelial function. The ideal intervention effect of improving NO level was more likely to be obtained by taking the exercise prescription of high-intensity aerobic exercise with a single exercise duration of 35-50 min, 3-4 times/week for 10-12 weeks; the ideal intervention effect of improving ET-1 was more likely to be obtained by taking the exercise prescription of oderate -intensity resistance exercise with a single exercise duration of ≥60 min, 6 times/week for 15-18 weeks., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Advancing age increases cardiovascular disease risk, in part, because of impaired glycocalyx thickness and endothelial dysfunction. Glycocalyx-targeted therapies, such as Endocalyx Pro, could improve both glycocalyx thickness and endothelial function in older adults; however, this has yet to be tested. We hypothesized that Endocalyx Pro supplementation would increase glycocalyx thickness and endothelial function in older adults. Twenty-three older adults aged 66 ± 7 yr (52% female) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arms study to investigate the effect of 12-wk Endocalyx Pro supplementation (3,712 mg/day) on glycocalyx thickness and endothelial function. Glycocalyx thickness was assessed using the GlycoCheck, and endothelial function was determined via brachial artery flow-mediated dilation (FMD). Between-group comparisons revealed Endocalyx Pro did not increase glycocalyx thickness in microvessels 4-25 µm ( P = 0.33), 4-7 µm ( P = 0.07), or 10-25 µm ( P = 0.47) in diameter when compared with placebo. In addition, Endocalyx Pro did not significantly improve FMD [mean ratio (95%) confidence interval [CI]) for between-group comparisons, 1.16 (0.77-1.74); P = 0.48]. However, Endocalyx Pro improved FMD normalized to shear rate (SR) area under the curve [mean ratio (95% CI) for between-group comparisons, 2.41 (1.14,4.13); P = 0.001]. Moreover, Endocalyx Pro increased capillary glycocalyx thickness more than placebo in individuals not taking antihypertensive medication [mean difference (95% CI) for between-group comparison, -0.08 (-0.15, -0.01); P = 0.02]. Our pilot study suggests that Endocalyx Pro supplementation is feasible in older adults but has no measurable effect on overall glycocalyx thickness and FMD. However, Endocalyx Pro may have select effects on capillary glycocalyx thickness and FMD normalized to shear rate among older adults, but further investigation is warranted. NEW & NOTEWORTHY Endothelial glycocalyx thickness and vascular endothelial function decline with advancing age. Endocalyx Pro is a glycocalyx-targeted therapy that may improve endothelial glycocalyx thickness and vascular endothelial function in older adults. This study demonstrated that 12-wk Endocalyx Pro supplementation did not improve overall endothelial glycocalyx thickness or flow-mediated dilation in older adults; however, Endocalyx Pro did increase capillary glycocalyx thickness in individuals not taking antihypertensive medication and improve flow-mediated dilation normalized to the shear stimulus.

The aim of the present study was to investigate the effects of multicomponent training on adropin, endothelial function, insulin resistance, and sleep quality in overweight older adults. In this randomized controlled study, 40 overweight older adults were randomly divided into training and control groups. The multicomponent training program including aerobic, resistance, and balance exercise was followed for 8 weeks, 3 days a week. Study variables were measured 48 hr before and after the intervention. After 8 weeks of multicomponent training, adropin (p = .01), nitric oxide (p = .01), and maximal oxygen uptake (VO2max; p = .002) increased, and glucose (p = .001), insulin (p = .001), insulin resistance (p = .01), systolic blood pressure (p = .01), and sleep disorders (p = .01) decreased significantly. Also, Pearson's test results showed a significant inverse relationship between adropin level (p = .01 and r = -.55) and glucose (p = .01 and r = -.51) with sleep disorders. It seems that multicomponent training increases adropin and improves insulin resistance, endothelial function, and sleep quality in older adults.

Objective: To investigate whether women with unexplained recurrent pregnancy loss have impaired arterial vascular health compared with controls, and to evaluate whether this is modifiable by exercise., Design: Experimental case-control pilot study., Setting: University medical centre in the Netherlands., Population: Twelve women with unexplained recurrent pregnancy loss, 11 nulliparous women and 19 primiparous women with a history of uncomplicated pregnancies., Methods: In all three groups we measured baseline characteristics, metabolic components and arterial vascular health, and repeated this in women with unexplained recurrent pregnancy loss after 1 month of protocolled and supervised cycle training., Main Outcome Measures: Differences in arterial vascular health between women with unexplained recurrent pregnancy loss and controls, and the effect of exercise on arterial vascular health in women with unexplained recurrent pregnancy loss., Results: Women with unexplained recurrent pregnancy loss have a significantly increased carotid intima media thickness in comparison with both controls (both P < 0.01), a significantly decreased brachial endothelial dependent flow-mediated vasodilation in comparison with both controls (nulliparous: P < 0.01; primiparous: P = 0.05) and a significantly decreased femoral endothelial dependent flow-mediated vasodilation in comparison with primiparous women (P = 0.01). The endothelium independent glyceryl trinitrate response was similar in all groups. With 1 month of exercise, the carotid intima media thickness decreased significantly by 7% (P = 0.05) and the femoral FMD increased significantly by 10% (P = 0.01) in women with unexplained recurrent pregnancy loss., Conclusions: Women with unexplained recurrent pregnancy loss have an impaired vascular health in comparison with controls. This impaired arterial vascular health can be improved by exercise., (© 2023 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

A key mechanism promoting vascular endothelial dysfunction is mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function in preclinical models by lowering mtROS. However, the effects of mtROS on endothelial function in exercising and non-exercising adults is limited. In a double-blind, randomized, placebo-controlled crossover study design 23 (10 M/13 F, age 62.1 ± 11.5 years) middle-aged and older (MA/O, ≥45 years) adults were divided into two groups: exercisers (EX, n = 11) and non-exercisers (NEX, n = 12). All participants had endothelial function (brachial artery flow-mediated dilatation, FMD BA ) measured before and ∼1 h after mitoquinone mesylate (MitoQ) (single dose, 80 mg) and placebo supplementation. A two-way repeated measures ANOVA was used to determine the effects of MitoQ and placebo on FMD BA . Pearson correlations assessed the association between the change in FMD BA with MitoQ and baseline FMD BA and cardiorespiratory fitness (CRF). Compared with placebo, MitoQ increased FMD BA in NEX by + 2.1% (MitoQ pre: 4.9 ± 0.4 vs. post: 7.0 ± 0.4 %, P = 0.004, interaction) but not in EX (P = 0.695, interaction). MitoQ also increased endothelial function in adults with a FMD BA <6% (P < 0.0001, interaction) but not >6% (P = 0.855, interaction). Baseline FMD BA and CRF were correlated (r = 0.44, P = 0.037), whereas the change in FMD BA with MitoQ was inversely correlated with CRF (r = -0.66, P < 0.001) and baseline FMD BA (r = -0.73, P < 0.0001). The relationship between the change in FMD BA and baseline FMD BA remained correlated after adjusting for CRF (r = -0.55, P = 0.007). These data demonstrate that MitoQ acutely improves FMD BA in NEX and EX adults who have a baseline FMD BA <6%. KEY POINTS: A key age-related change contributing to increased cardiovascular disease (CVD) risk is vascular endothelial dysfunction due to increased mitochondrial-derived reactive oxygen species (mtROS). Aerobic exercise preserves endothelial function via suppression of mtROS in preclinical models but the evidence in humans is limited. In the present study, a single dose of the mitochondria-targeted antioxidant, mitoquinone mesylate (MitoQ), increases endothelial function in non-exercisers with lower cardiorespiratory fitness (CRF) but not in exercisers with higher CRF. The acute effects of MitoQ on endothelial function in middle-aged and older adults (MA/O) are influenced by baseline endothelial function independent of CRF. These data provide initial evidence that the acute MitoQ-enhancing effects on endothelial function in MA/O adults are influenced, in part, via CRF and baseline endothelial function., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Endothelial dysfunction develops with age and may precede cardiovascular disease. Animal data suggest that T-type calcium channels play an important role in endothelial function, but data from humans are lacking. This study included 15 healthy, sedentary, elderly males for a double blinded, randomized controlled trial. For 8 weeks, they were given 40 mg/day of either efonidipine (L- and T-type calcium channel blocker (CCB)) or nifedipine (L-type CCB). Vascular function was evaluated by graded femoral arterial infusions of acetylcholine (ACh; endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator) both with and without co-infusion of N-acetylcysteine (NAC; antioxidant). We measured leg blood flow and mean arterial pressure and calculated leg vascular conductance to evaluate the leg vascular responses. Despite no significant change in blood pressure in either group, we observed higher leg blood flow responses (Δ 0.43 ± 0.45 l/min, P = 0.006) and leg vascular conductance (Δ 5.38 ± 5.67 ml/min/mmHg, P = 0.005) to intra-arterial ACh after efonidipine, whereas there was no change in the nifedipine group, and no differences between groups. We found no upregulation of endothelial nitric oxide synthase in vastus lateralis muscle biopsies within or between groups. Smooth muscle cell responsiveness was unaltered by efonidipine or nifedipine. Intravenous co-infusion of NAC did not affect endothelium-dependent vasodilatation in either of the CCB groups. These results suggest that 8 weeks' inhibition of T- and L-type calcium channels augments endothelium-dependent vasodilatory function in healthy elderly males. Further studies are required to elucidate if T-type calcium channel inhibition can counteract endothelial dysfunction., (© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Our objective was to explore whether consuming the same high-fat/sugar beverage affects endothelial function differently depending on whether it is presented as "unhealthy" [accurate high calorie (kcal), fat, and sugar information displayed] versus "healthy" (inaccurate low kcal, fat, and sugar information displayed). Twenty-five, young (21 ± 2 yr), healthy, food-stress/shame-prone women completed three conditions: milkshake consumption (540 kcal, 80 g sugar, and 14 g fat) where correct, "unhealthy" nutritional information was shown to participants (milkshake condition), consumption of the same milkshake but with incorrect, "healthy" information shown to participants (100 kcal, 3 g sugar, and 4 g fat; sham-nutrishake condition), and water consumption (control condition). Pre- and postbeverage we assessed 1 ) endothelial function via standard brachial artery flow-mediated dilation (FMD); 2 ) perceived shame, stress, beverage healthiness, and harm; and 3 ) blood (plasma) glucose, insulin, triglycerides and oral fluid cortisol, and tumor necrosis factor-alpha (TNFα) receptor binding. Glucose, triglycerides, and insulin increased in the milkshake and sham-nutrishake conditions ( P < 0.05). The milkshake was perceived as less healthy ( P < 0.001) and more harmful ( P < 0.001) than the sham-nutrishake. Shame, stress, oral fluid cortisol and TNFα receptor binding did not increase postconsumption. FMD decreased after the milkshake condition (pre: 7.4 ± 3.3%; post-60 min: 4.9 ± 2.9%; post-90 min: 4.5 ± 3.1%, P < 0.001) but not the sham-nutrishake (pre: 5.7 ± 2.2%; post-60 min: 5.5 ± 2.6%; post-90 min: 5.0 ± 2.4%, P = 0.43) or control conditions (pre: 7.0 ± 2.6%; post-60 min: 6.6 ± 4.1%; post-90 min: 6.0 ± 3.2%, P = 0.29). Shear rate stimulus covariation did not alter FMD results. Lower perceived beverage healthiness was significantly associated with a greater reduction in FMD (ρ = 0.36, P = 0.002). In conclusion, a high-fat/sugar milkshake reduced FMD only when presented as high in fat, sugar, and calories. This suggests that perceptions about nutritional information contribute to the impact of food intake on endothelial function and that nocebo effects could be involved in cardiovascular disease etiology. NEW & NOTEWORTHY This was the first study to investigate how perceived nutritional content influences the impact of a high-sugar/fat beverage on endothelial function. We found that a high-sugar/fat beverage only reduced endothelial function when it was presented to participants as high in calories, fat, and sugar. This suggests that perceived nutritional information contributes to the impact of high sugar and fat intake on endothelial function.

Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired vascular endothelial function that may be improved by hydroxy-methylglutaryl-CoA (HMG-CoA) reductase enzyme inhibition. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on peripheral vascular function and biomarkers of inflammation and oxidative stress in 16 patients with HFpEF [Statin: n = 8, 74 ± 6 yr, ejection fraction (EF) 52-73%; Placebo: n = 8, 67 ± 9 yr, EF 56-72%]. Flow-mediated dilation (FMD) and sustained-stimulus FMD (SS-FMD) during handgrip (HG) exercise, reactive hyperemia (RH), and blood flow during HG exercise were evaluated to assess conduit vessel function, microvascular function, and exercising muscle blood flow, respectively. FMD improved following statin administration (pre, 3.33 ± 2.13%; post, 5.23 ± 1.35%; P < 0.01), but was unchanged in the placebo group. Likewise, SS-FMD, quantified using the slope of changes in brachial artery diameter in response to increases in shear rate, improved following statin administration (pre: 5.31 e -5  ± 3.85 e -5  mm/s -1 ; post: 8.54 e -5  ± 4.98 e -5  mm/s -1 ; P = 0.03), with no change in the placebo group. Reactive hyperemia and exercise hyperemia responses were unchanged in both statin and placebo groups. Statin administration decreased markers of lipid peroxidation (malondialdehyde, MDA) (pre, 0.652 ± 0.095; post, 0.501 ± 0.094; P = 0.04), whereas other inflammatory and oxidative stress biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular function or exercising limb blood flow, in patients with HFpEF, which may be due in part to reductions in oxidative stress. NEW & NOTEWORTHY This is the first study to investigate the impact of statin administration on vascular function and exercise hyperemia in patients with heart failure with preserved ejection fraction (HFpEF). In support of our hypothesis, both conventional flow-mediated dilation (FMD) testing and brachial artery vasodilation in response to sustained elevations in shear rate during handgrip exercise increased significantly in patients with HFpEF following statin administration, beneficial effects that were accompanied by a decrease in biomarkers of oxidative damage. However, contrary to our hypothesis, reactive hyperemia and exercise hyperemia were unchanged in patients with HFpEF following statin therapy. These data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular reactivity or exercising muscle blood flow in patients with HFpEF, which may be due in part to reductions in oxidative stress.

Background: Vascular dysfunction constitutes the etiology of many diseases, such as myocardial infarction and hypertension, with the disruption of redox homeostasis playing a role in the imbalance of the vasomotor control mechanism. Our group previously has shown that thyroid hormones exert protective effects on the aortic tissue of infarcted rats by improving angiogenesis signaling., Objective: Investigate the role of triiodothyronine (T3) on vascular response, exploring its effects on isolated aortas and whether there is an involvement of vascular redox mechanisms., Methods: Isolated aortic rings (intact- and denuded-endothelium) precontracted with phenylephrine were incubated with T3 (10-8, 10-7, 10-6, 10-5, and 10-4 M), and tension was recorded using a force-displacement transducer coupled with an acquisition system. To assess the involvement of oxidative stress, aortic rings were preincubated with T3 and subsequently submitted to an in vitro reactive oxygen species (ROS) generation system. The level of significance adopted in the statistical analysis was 5%., Results: T3 (10-4 M) promoted vasorelaxation of phenylephrine precontracted aortic rings in both intact- and denuded-endothelium conditions. Aortic rings preincubated in the presence of T3 (10-4 M) also showed decreased vasoconstriction elicited by phenylephrine (1 µM) in intact-endothelium preparations. Moreover, T3 (10-4 M) vasorelaxation effect persisted in aortic rings preincubated with NG-nitro-L-arginine methylester (L-NAME, 10 µM), a nonspecific NO synthase (NOS) inhibitor. Finally, T3 (10-4 M) exhibited, in vitro, an antioxidant role by reducing NADPH oxidase activity and increasing SOD activity in the aorta's homogenates., Conclusion: T3 exerts dependent- and independent-endothelium vasodilation effects, which may be related to its role in maintaining redox homeostasis.

Biological sex is a salient factor in exercise-induced vascular adaptation. Although a male bias is apparent in the literature, the methodological quality of available studies in females is not yet known. This systematic review with narrative synthesis aimed to assess available evidence of exercise interventions on endothelial function, measured using flow-mediated dilation, in otherwise healthy individuals and athletes. A standardized audit framework was applied to quantify the representation of female participants. Using a tiered grading system, studies that met best-practice recommendations for conducting physiological research in females were identified. A total of 210 studies in 5,997 participants were included, with 18% classified as athletes. The primary exercise mode and duration were aerobic (49%) and acute (61%), respectively. Despite 53% of studies ( n = 111) including at least one female, female participants accounted for only 39% of the total study population but 49% of the athlete population. Majority (49%) of studies in females were conducted in premenopausal participants. No studies in naturally menstruating, hormonal contraceptive-users or in participants experiencing menstrual irregularities met all best-practice recommendations. Very few studies (∼5%) achieved best-practice methodological guidelines for studying females and those that did were limited to menopause and pregnant cohorts. In addition to the underrepresentation of female participants in exercise-induced vascular adaptation research, there remains insufficient high-quality evidence with acceptable methodological control of ovarian hormones. To improve the overall methodological quality of evidence, adequate detail regarding menstrual status should be prioritized when including females in vascular and exercise research contexts.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide. CVDs are promoted by the accumulation of lipids and immune cells in the endothelial space resulting in endothelial dysfunction. Endothelial cells are important components of the vascular endothelium, that regulate the vascular flow. The imbalance in the production of vasoactive substances results in the loss of vascular homeostasis, leading the endothelial dysfunction. Thus, endothelial dysfunction plays an essential role in the development of atherosclerosis and can be triggered by different cardiovascular risk factors. On the other hand, the 17β-estradiol (E2) hormone has been related to the regulation of vascular tone through different mechanisms. Several compounds can elicit estrogenic actions similar to those of E2. For these reasons, they have been called endocrine-disrupting compounds (EDCs). This review aims to provide up-to-date information about how different EDCs affect endothelial function and their mechanistic roles in the context of CVDs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The dynamic nature of the microtubule network is dependent in part by post-translational modifications (PTMs) - particularly through acetylation, which stabilizes the microtubule network. Whether PTMs of the microtubule network in vascular smooth muscle cells (VSMCs) contribute to the pathophysiology of hypertension is unknown. The aim of this study was to determine the acetylated state of the microtubule network in the mesenteric arteries of spontaneously hypertensive rats (SHR). Experiments were performed on male normotensive rats and SHR mesenteric arteries. Western blotting and mass spectrometry determined changes in tubulin acetylation. Wire myography was used to investigate the effect of tubacin on isoprenaline-mediated vasorelaxations. Isolated cells from normotensive rats were used for scanning ion conductance microscopy (SICM). Mass spectrometry and Western blotting showed that tubulin acetylation is increased in the mesenteric arteries of the SHR compared with normotensive rats. Tubacin enhanced the β-adrenoceptor-mediated vasodilatation by isoprenaline when the endothelium was intact, but attenuated relaxations when the endothelium was denuded or nitric oxide production was inhibited. By pre-treating vessels with colchicine to disrupt the microtubule network, we were able to confirm that the effects of tubacin were microtubule-dependent. Using SICM, we examined the cell surface Young's modulus of VSMCs, but found no difference in control, tubacin-treated, or taxol-treated cells. Acetylation of tubulin at Lys40 is elevated in mesenteric arteries from the SHR. Furthermore, this study shows that tubacin has an endothelial-dependent bimodal effect on isoprenaline-mediated vasorelaxation., (© 2024 The Author(s).)

Introduction: Endothelial dysfunction is the initial step in the pathogenesis of atherosclerosis; and it plays a central role in the development of cardiovascular diseases and many types of human diseases (diabetes, kidney failure, cancer, and viral infections). Strategies that are effective in protecting vascular endothelial function and retard or reversing endothelial dysfunction in the early stage appear to be potential in the prevention of vascular, cardiac, and many human diseases. Several studies have been carried out on the effects of yoga on endothelial function, but the results of these studies have not been synthesized. This study aimed at conducting a systematic review and meta-analysis to determine the effectiveness of yoga on endothelial function. Methods: A systematic review and meta-analysis of studies that assessed the effect of yoga practice on vascular endothelial function was done as per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Scopus, Google Scholar, and Cochrane controlled register of trials (CENTRAL) were searched from inception to August 2022. The search strategy was constructed around yoga-based techniques and endothelial function. All the yoga-based interventional studies on endothelial function or dysfunction were included in this review. A narrative synthesis and descriptive analysis were done due to the diverse methodology of selected studies. We carried out a formal meta-analysis of controlled trials that assessed the effect of yoga on flow-mediated dilatation (FMD), a measure of endothelial function. Results: A total of 18 studies were included for review involving 1043 participants. Yoga training showed improved endothelial function in 12 studies, whereas 6 studies did not find any statistically robust effect. Meta-analysis ( n  = 395 participants, 6-studies, 7 comparisons) showed an increase in brachial FMD by yoga practice (mean difference = -1.23%; 95% confidence interval -2.23 to -0.23; p  = 0.02). The heterogeneity between the studies was 43% (Tau 2  = 0.70, χ 2  = 10.49). The risk of bias was low to moderate in these studies. No adverse effects were reported. Conclusions: Yoga practice improved endothelial function. Yoga could be a safe and potential integrative medicine to improve endothelial function. However, as the statistical heterogeneity, that is, variation in the FMD among the studies was moderate, large clinical trials are necessary for its clinical recommendations.

Sauna has been linked to a reduction of cardiovascular disease risk and is a promising nonpharmacological treatment for populations at risk of cardiovascular disease. This study examined the vascular response to an acute bout of sauna heating in young and middle-aged individuals. Ten young (25 ± 4 yr, 6 males and 4 females) and eight middle-aged adults (56 ± 4 yr, 4 males and 4 females) underwent 40 min of sauna exposure at 80°C. Esophageal and intramuscular temperatures, brachial and superficial femoral artery blood flow, artery diameter, and shear rates were recorded at baseline and following heat exposure. Brachial artery flow-mediated dilation (FMD) was measured at baseline and following 90 min of recovery. Esophageal and muscle temperatures increased similarly in the young and middle-aged adults by 1.5 ± 0.53 and 1.95 ± 0.70°C, respectively ( P < 0.05). The shear rate increased by 170-200% ( P < 0.001), while blood flow increased by 180-390% ( P < 0.001) in the superficial femoral and brachial arteries, respectively, and did not differ between age groups ( P = 0.190-0.899). Systolic blood pressure was reduced from 135 ± 17 to 122 ± 20 mmHg ( P = 0.017) in middle-aged participants. These data indicate that young and middle-aged adults have similar vascular responses to acute sauna heating. NEW & NOTEWORTHY Sauna therapy has been shown to improve cardiovascular health and function in older adults and individuals with cardiovascular disease risk factors. Specifically, improvements in vascular function have been reported and have been attributed to the increased hemodynamic stimuli on the vasculature associated with thermal stress. The present study quantified this hemodynamic response to a sauna protocol associated with improved cardiovascular health across the lifespan. Our data show that middle-aged adults have the same shear rate and blood flow response to sauna as young adults.

Mechanical forces influence different cell types in our bodies. Among the earliest forces experienced in mammals is blood movement in the vascular system. Blood flow starts at the embryonic stage and ceases when the heart stops. Blood flow exposes endothelial cells (ECs) that line all blood vessels to hemodynamic forces. ECs detect these mechanical forces (mechanosensing) through mechanosensors, thus triggering physiological responses such as changes in vascular diameter. In this review, we focus on endothelial mechanosensing and on how different ion channels, receptors, and membrane structures detect forces and mediate intricate mechanotransduction responses. We further highlight that these responses often reflect collaborative efforts involving several mechanosensors and mechanotransducers. We close with a consideration of current knowledge regarding the dysregulation of endothelial mechanosensing during disease. Because hemodynamic disruptions are hallmarks of cardiovascular disease, studying endothelial mechanosensing holds great promise for advancing our understanding of vascular physiology and pathophysiology.

Inspiratory resistance training (IRT) yields significant reductions in resting blood pressure and improves vascular endothelial function. Our objective was to quantify the acute effects of IRT on brachial artery flow-mediated dilation (FMD) and shear rates (SRs) in healthy men and women. Twenty young adults (22.9 ± 3.4 years; 10 male, 10 female) completed a single bout of IRT or Rest condition in a randomized crossover design. Brachial artery FMD was performed before, 10 min after, and 40 min after the assigned condition. Brachial artery blood flow velocities were collected during IRT, separated by breathing cycle phase, and converted into SRs. FMD improved 10 min post-IRT (+1.86 ± 0.61%; p = 0.025) but returned to baseline by 40 min post-IRT (p = 0.002). Anterograde SR decreased by 10% and retrograde SR increased 102% during resisted inspiration, relative to baseline SR (p < 0.001). Anterograde SR increased by 7% in men and women (p < 0.001) and retrograde SR decreased by 12% in women but not men (p = 0.022) during unresisted expiration, relative to baseline SR. A single bout of IRT elicits a transient enhancement in FMD in both men and women. Acute IRT-related enhancements in SRs may contribute to sustained improvements in FMD that have been reported previously., (© 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Purpose: Postprandial hyperglycemia is assumed to have a negative impact on flow-mediated dilation (FMD), an index of endothelial function, and blood flow of the peripheral conduit arteries. This study aimed to determine whether the enhancement of postprandial hyperglycemia by skipping breakfast accelerates endothelial dysfunction and reduces the blood flow in the brachial artery in young men., Methods: Using a randomized cross-over design, ten healthy men completed two trials: with and without breakfast (Eating and Fasting trials, respectively). Venous blood sampling and brachial FMD tests were conducted before, 30, 60, 90, and 120 min after a 75-g oral glucose tolerance test (OGTT)., Results: Skipping breakfast boosted post-OGTT glucose levels than having breakfast (P = 0.01). The magnitude of the decrease in FMD via OGTT did not vary between trials (main effect of trial P = 0.55). Although brachial blood flow tended to decrease after OGTT in both trials (interaction and main effect of time P = 0.61 and P = 0.054, respectively), the decrease in blood flow following OGTT was greater in the Fasting trial than in the Eating trial (main effect of trial, mean difference =  - 15.8 mL/min [95%CI =  - 25.6 to - 6.0 mL/min], P < 0.01)., Conclusion: Skipping breakfast did not enhance the magnitude of the decrease in FMD following glucose loading, but did accelerate hyperglycemia-induced reduction in brachial blood flow. Current findings suggest that even missing one breakfast has negative impacts on the blood flow regulation of the peripheral conduit arteries in young men who habitually eat breakfast., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Aging leads to vascular endothelial dysfunction and muscle impairment. While resistance exercise improves muscular function, its acute effects on vascular function vary in the literature, with some studies reporting detrimental effects. These findings indicate the need for exercises that optimize muscle function without compromising vascular function. Reformer Pilates (RP) is a low-impact exercise involving an adjustable sliding platform. However, the acute effects of RP on vascular function among older adults remain unknown. Therefore, this study aimed to investigate the acute effects of RP on vascular function in older adults., Methods: Overall, 17 participants (age: 65 ± 2.76 years, body mass index: 23.42 ± 3.68 kg/m2) were examined and assigned to control and RP conditions under a randomized crossover design. The RP condition involved a 3.5-5 omnibus perceived exertion scale with 19 exercise postures for 60 min. Brachial artery flow-mediated dilation (FMD), brachial-ankle pulse wave velocity (baPWV), and blood pressure were measured at baseline and 0, 10, 30, and 60 min after exercise., Results: RP significantly improved FMD at all time points compared with that at baseline (p &lt; 0.05). baPWV increased at 0 min post-RP but returned to baseline levels at other time points. Additionally, RP showed improved FMD at 0, 10, and 30 min compared with that in the control condition (p &lt; 0.05). However, no significant differences were observed in blood pressure or mean arterial pressure in either condition., Conclusion: RP enhanced FMD and regulated blood pressure for approximately 60 min post-exercise, suggesting its suitability for older adults to enhance vascular function and control blood pressure during exercise. Nonetheless, longitudinal resistance training intervention studies are needed to validate these findings., (© 2024 S. Karger AG, Basel.)

Aims: Transient receptor potential vanilloid 2 (TRPV2) channels are expressed in both smooth muscle and endothelial cells and participate in vascular mechanotransduction and sensing of high temperatures and lipids. Nevertheless, the impact of TRPV2 channel activation by agonists on the coordinated and cell-type specific modulation of vasoreactivity is unknown., Main Methods: Aorta from 2- to 4-months-old male Oncins France 1 mice was dissected and mounted in tissue baths for isometric tension measurements. TRPV2 channel expression was assessed by immunofluorescence and western blot in mice aortas and in cultured A7r5 rat aortic smooth muscle cells., Key Findings: TRPV2 channels were expressed in all three mouse aorta layers. Activation of TRPV2 channels with probenecid evoked endothelium-dependent relaxations through a mechanism that involved activation of smooth muscle K ir and K v channels. In addition, TRPV2 channel inhibition with tranilast increased endothelium-independent relaxations to probenecid and this effect was abrogated by the K ATP channel blocker glibenclamide, revealing that smooth muscle TRPV2 channels induce negative feedback on probenecid relaxations mediated via K ATP channel inhibition. Exposure to the NO donor sodium nitroprusside increased TRPV2 channel translocation to the plasma membrane in cultured smooth muscle cells and enhanced negative feedback on probenecid relaxations., Significance: In conclusion, we present the first evidence that TRPV2 channels may modulate vascular tone through a balance of opposed inputs from the endothelium and the smooth muscle leading to net vasodilation. The fact that TRPV2 channel-induced activity can be amplified by NO emphasizes the pathophysiological relevance of these findings., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be interpreted as a potential conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Endothelial function is commonly determined via the ultrasound-based flow-mediated dilation (FMD) technique which assesses arterial dilation in response to a hyperemia response following distal cuff occlusion. However, the low-flow-mediated constriction (L-FMC) response during cuff-induced ischemia is often overlooked. L-FMC provides unique information regarding endothelial function, but vascular researchers may be unclear on what this metric adds. Therefore, the objective of this review was to examine the mechanistic determinants and participant-level factors of L-FMC. Existing mechanistic studies have demonstrated that vasoreactivity to low flow may be mediated via non-nitric oxide vasodilators (i.e., endothelial hyperpolarizing factors and/or prostaglandins), inflammatory markers, and enhancement of vasoconstriction via endothelin-1. In general, participant-level factors such as aging and presence of cardiovascular conditions generally are associated with attenuated L-FMC responses. However, the influence of sex on L-FMC is unclear with divergent results between L-FMC in upper versus lower limb vessels. The ability of aerobic exercise to augment L-FMC (i.e., make more negative) is well supported, but there is a major gap in the literature concerning the mechanistic underpinnings of this observation. This review summarizes that while larger L-FMC responses are generally healthy, the impact of interventions to augment/attenuate L-FMC has not included mechanistic measures that would provide insight into non-nitric oxide-based endothelial function. Clarifications to terminology and areas of further inquiry as it relates to the specific pharmacological, individual-level factors, and lifestyle behaviors that impact L-FMC are highlighted. A greater integration of mechanistic work alongside applied lifestyle interventions is required to better understand endothelial cell function to reductions in local blood flow., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Take Home Message: Our case study indicated that a bifurcated brachial artery exhibited worse vasodilatory responses relative to an intact contralateral artery., Competing Interests: The author has no conflicts of interest to report.

There is some evidence that transient endothelial dysfunction induced by acute hyperglycemia may be attenuated by a single bout of aerobic exercise. However, the impact of aerobic exercise training on acute hyperglycemia-induced endothelial dysfunction has not been explored. The purpose of this study was to determine the impact of aerobic exercise training on the endothelial function response to acute hyperglycemia. Brachial artery flow-mediated dilation (FMD) was assessed in 24 healthy males (21 ± 1 years) pre-, 60 and 90 min post ingestion of 75 g of glucose. Participants completed a four-week control (CON; n = 13) or exercise training (EX; n = 11) intervention. The EX group completed four weeks of cycling exercise (30 min, 4×/week at 65% work rate peak). Cardiorespiratory fitness ([Formula: see text]O 2 peak) increased and resting HR decreased in EX, but not CON post-intervention (p < 0.001). Glucose and insulin increased (p < 0.001) following glucose ingestion, with no significant difference pre- and post-intervention. In contrast to previous research, FMD was unaffected by glucose-ingestion, pre- and post-intervention in both groups. In conclusion, acute hyperglycemia did not impair endothelial function, before or after exercise training. Relatively high baseline fitness ([Formula: see text]O 2 peak ~ 46 mL/kg/min) and young age may have contributed to the lack of impairment observed. Further research is needed to examine the impact of exercise training on hyperglycemia-induced impairments in endothelial function in sedentary males and females., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vascular tone regulation is a key event in controlling blood flow in the body. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) help regulate the vascular tone. Abnormal vascular responsiveness to various stimuli, including constrictors and dilators, has been observed in pathophysiological states although EC and VSMC coordinate to maintain the exquisite balance between contraction and relaxation in vasculatures. Thus, investigating the mechanisms underlying vascular tone abnormality is very important in maintaining vascular health and treating vasculopathy. Increased intracellular free Ca 2+ concentration ([Ca 2+ ]i) is one of the major triggers initiating each EC and VSMC response. Transient receptor potential vanilloid family member 4 (TRPV4) is a Ca 2+ -permeable non-selective ion channel, which is activated by several stimuli, and is presented in both ECs and VSMCs. Therefore, TRPV4 plays an important role in vascular responses. Emerging evidence indicates the role of TRPV4 on the functions of ECs and VSMCs in various pathophysiological states, including hypertension, diabetes, and obesity. This review focused on the link between TRPV4 and the functions of ECs/VSMCs, particularly its role in vascular tone and responsiveness to vasoactive substances., Competing Interests: Declaration of competing interest There are no potential conflicts of interest among the authors regarding the publication of this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)