The vascular response to acute sauna heating is similar in young and middle-aged adults.

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.

Omega-3 fatty acids and endothelial function: A GRADE-assessed systematic review and meta-analysis.

INTRODUCTION: N-3 polyunsaturated fatty acids (PUFAs) supplementation has been reported to have an impact on flow-mediated dilatation (FMD), a conventionally used clinical technique for estimating endothelial dysfunction. However, its proven effects on endothelial function are unclear. This systematic review and meta-analysis were conducted to evaluate the effects of n-3 PUFAs supplementation on FMD of the brachial artery. METHOD: This study was performed following the PRISMA guidelines. To identify eligible RCTs, a systematic search was completed in PubMed/Medline, Scopus and Web of Science using relevant keywords. A fixed- or random-effects model was utilized to estimate the weighted mean difference (WMD) and 95% confidence interval (95% CI). RESULTS: Thirty-two studies (with 35 arms) were included in this meta-analysis, involving 2385 subjects with intervention duration ranging from 4 to 48 weeks. The pooled meta-analysis demonstrated a significant effect of omega-3 on FMD (WMD = 0.8%, 95% CI = 0.3-1.3, p = .001) and heterogeneity was significant (I2 = 82.5%, p < .001). CONCLUSION: We found that n-3 PUFA supplementation improves endothelial function as estimated by flow-mediated dilatation of the brachial artery.

The acute effect of whole-body heat therapy on peripheral and cerebral vascular reactivity in Black and White females.

Among females in the U.S., Black females suffer the most from cardiovascular disease and stroke. While the reasons for this disparity are multifactorial, vascular dysfunction likely contributes. Chronic whole-body heat therapy (WBHT) improves vascular function, but few studies have examined its acute effect on peripheral or cerebral vascular function, which may help elucidate chronic adaptative mechanisms. Furthermore, no studies have investigated this effect in Black females. We hypothesized that Black females would have lower peripheral and cerebral vascular function relative to White females and that one session of WBHT would mitigate these differences. Eighteen young, healthy Black (n = 9; 21 ± 3 yr; BMI: 24.7 ± 4.5 kg/m2) and White (n = 9; 27 ± 3 yr; BMI: 24.8 ± 4.1 kg/m2) females underwent one 60 min session of WBHT (49 °C water via a tube-lined suit). Pre- and 45 min post-testing measures included post-occlusive forearm reactive hyperemia (peripheral microvascular function, RH), brachial artery flow-mediated dilation (peripheral macrovascular function, FMD), and cerebrovascular reactivity (CVR) to hypercapnia. Prior to WBHT, there were no differences in RH, FMD, or CVR (p > 0.05 for all). WBHT improved peak RH in both groups (main effect of WBHT: 79.6 ± 20.1 cm/s to 95.9 ± 30.0 cm/s; p = 0.004, g = 0.787) but not Δ blood velocity (p > 0.05 for both groups). WBHT improved FMD in both groups (6.2 ± 3.4 % to 8.8 ± 3.7 %; p = 0.016, g = 0.618) but had no effect on CVR in either group (p = 0.077). These data indicate that one session of WBHT acutely improves peripheral micro- and macrovascular but not cerebral vascular function in Black and White females.

Use of ankle-brachial pressure index to assess patient suitability for lower limb compression.

BACKGROUND: Compression therapy is a safe, effective treatment for lower leg conditions such as lymphatic insufficiency and venous hypertension. The most common method of arterial assessment is the calculation of a patient's ankle-brachial pressure index (ABPI). The need for ABPI is highlighted in many best practice statement and local policies. ABPI compares the arterial flow of the arms and the legs, providing a ratio used to determine the presence and severity of peripheral artery disease and assess whether a patient is suitable for compression therapy. AIM: This study critically reviews and analyses findings from contemporary literature with the aim of evaluating the effectiveness of the ABPI screening tool. METHOD: A structured literature review using a narrative approach was carried out. RESULTS: Four studies were identified for inclusion, which involved medical, nursing and allied health professional staff in primary and secondary care, with a total of 51 patients. Analysis generated eight themes: appropriateness of the ABPI tool; clinician education; referral process; access to appropriate equipment; lack of time to conduct the assessment; competence; associated costs; and role definition. CONCLUSION: It is important to undertake a holistic assessment of the patient, incorporating ABPI assessment where not contraindicated. Further research to explore patient experience and safety when assessing a patient's suitability for lower limb compression therapy is required.

Non-pharmacological interventions for vascular health and the role of the endothelium.

The most common non-pharmacological intervention for both peripheral and cerebral vascular health is regular physical activity (e.g., exercise training), which improves function across a range of exercise intensities and modalities. Numerous non-exercising approaches have also been suggested to improved vascular function, including repeated ischemic preconditioning (IPC); heat therapy such as hot water bathing and sauna; and pneumatic compression. Chronic adaptive responses have been observed across a number of these approaches, yet the precise mechanisms that underlie these effects in humans are not fully understood. Acute increases in blood flow and circulating signalling factors that induce responses in endothelial function are likely to be key moderators driving these adaptations. While the impact on circulating factors and environmental mechanisms for adaptation may vary between approaches, in essence, they all centre around acutely elevating blood flow throughout the circulation and stimulating improved endothelium-dependent vascular function and ultimately vascular health. Here, we review our current understanding of the mechanisms driving endothelial adaptation to repeated exposure to elevated blood flow, and the interplay between this response and changes in circulating factors. In addition, we will consider the limitations in our current knowledge base and how these may be best addressed through the selection of more physiologically relevant experimental models and research. Ultimately, improving our understanding of the unique impact that non-pharmacological interventions have on the vasculature will allow us to develop superior strategies to tackle declining vascular function across the lifespan, prevent avoidable vascular-related disease, and alleviate dependency on drug-based interventions.

[Evaluation of diagnostic efficacy of artery elasticity and endothelial function indexes for coronary heart disease with blood stasis syndrome in postmenopausal women by Logistic regression combined with ROC curve model].

The present study explored the correlation of coronary heart disease(CHD) with blood stasis syndrome in postmenopausal women with artery elasticity and endothelial function indexes and evaluated the diagnostic efficacy of the prediction model via logistic regression and receiver operating characteristic(ROC) curve model. A retrospective comparison was made between 366 postmenopausal CHD patients from August 1, 2020, to September 30, 2021, in the Department of Cardiology of Integrated Traditional Chinese and Western Medicine of China-Japan Friendship Hospital, who were divided into the blood stasis syndrome group(n=196) and the non-blood stasis syndrome group(n=170). General clinical characteristics of the two groups were compared. Multivariate logistic regression analysis was used to probe the correlation of CHD with blood stasis syndrome in postmenopausal women with brachial-ankle pulse wave velocity(baPWV), ankle-brachial index(ABI), and flow-mediated dilatation(FMD), and the ROC curve was drawn to evaluate the diagnostic efficiency of the prediction model. Multivariate logistic regression analysis showed that the correlation coefficients of CHD with blood stasis syndrome in postmenopausal women with baPWV, ABI, and FMD were 1.123, 0.109, and 0.719, respectively(P=0.004, P=0.005, P<0.001),and the regression equation for predicting probability P was P=1/[1+e~(-(3.131+0.116×baPWV-2.217×ABI-0.330×FMD))]. ROC curve analysis suggested that in the context of baPWV≥19.19 m·s~(-1) or ABI≤1.22 or FMD≤9.7%, it was of great significance to predict the diagnosis of CHD with blood stasis syndrome in postmenopausal women. The AUC of baPWV, ABI, FMD, and prediction probability P was 0.763, 0.607, 0.705, and 0.836, respectively. The AUC of prediction probability P was higher than that of each index alone(P<0.001), and the sensitivity and specificity were 0.888 and 0.647, respectively. The results demonstrate that baPWV, ABI, and FMD are independently correlated with CHD with blood stasis syndrome in postmenopausal women, and show certain independent predictive abilities(P<0.05). The combined evaluation of the three possesses the best diagnostic efficiency.

Acute heat exposure protects against endothelial ischemia-reperfusion injury in aged humans.

Nonpharmacological therapies that protect against endothelial ischemia-reperfusion injury (I/R) remain limited in aged adults. Acute heat exposure protects against endothelial I/R injury in young adults, but its efficacy has never been explored in aged adults. Therefore, we tested the hypothesis that acute heat exposure would prevent the attenuation of endothelium-dependent vasodilation after I/R injury in aged adults. Nine (2 men, 69 ± 8 yr) aged adults were exposed to a thermoneutral control condition or whole body passive heating (water-perfused suit) sufficient to increase body core temperature by 1.2°C. Experiments were separated by at least 7 days. Heat exposure was always performed first to time match the thermoneutral control condition. Endothelium-dependent vasodilation was assessed via flow-mediated dilation of the brachial artery before (pre-I/R) and after I/R injury (post-I/R), which was induced by 20 min of arm ischemia followed by 20 min of reperfusion. Flow-mediated dilation was reduced following I/R injury for the thermoneutral control condition (pre-I/R, 4.5 ± 2.9% vs. post-I/R, 0.9 ± 2.8%, P < 0.01), but was well maintained with prior heat exposure (pre-I/R, 4.4 ± 2.8% vs. post-I/R, 3.5 ± 2.8%, P = 0.5). Taken together, acute heat exposure protects against endothelial I/R injury in aged adults. These results highlight the therapeutic potential of heat therapy to prevent endothelial dysfunction associated with I/R injury in aged adults who are most at risk for an ischemic event.

The effect of grape (Vitis vinifera) seed extract supplementation on flow-mediated dilation, blood pressure, and heart rate: A systematic review and meta-analysis of controlled trials with duration- and dose-response analysis.

The objective of this systematic review and meta-analysis of controlled trials was to assess the long-term effect of grape seed extract (GSE) supplementation on flow-mediated dilation (FMD), systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) in adults. Web of Science, Scopus, Medline, Cochrane Library, and Google Scholar were searched up to May 24, 2021. Nineteen trials were included in this study. Weighted mean difference (WMD) and 95% confidence interval (CI) were calculated using a random-effects model. GSE supplementation significantly reduced DBP (WMD: -2.20 mmHg, 95% CI: -3.79 to -0.60, I2 = 88.8%) and HR (WMD: -1.25 bpm, 95% CI: -2.32 to -0.19, I2 = 59.5%) but had no significant effects on FMD (WMD: 1.02%, 95% CI: -0.62 to 2.66, I2 = 92.0%) and SBP (WMD: -3.55 mmHg, 95% CI: -7.59 to 0.49, I2 = 97.4%). Subgroup analysis revealed that the dose and duration of GSE administration and the characteristics of study participants could be sources of between-study heterogeneity. Significant non-linear relationships were found between DBP and the duration of GSE supplementation (P = 0.044) and its dose (P = 0.007). In conclusion, GSE may be beneficial for individuals with or at risk of cardiovascular disease because it may have hypotensive and HR-lowering properties.

Shear stress induced by acute heat exposure is not obligatory to protect against endothelial ischemia-reperfusion injury in humans.

Acute heat exposure protects against endothelial ischemia-reperfusion (I/R) injury in humans. However, the mechanism/s mediating this protective effect remain unclear. We tested the hypothesis that inhibiting the increase in shear stress induced by acute heat exposure would attenuate the protection of endothelial function following I/R injury. Nine (3 women) young healthy participants were studied under three experimental conditions: 1) thermoneutral control; 2) whole body heat exposure to increase body core temperature by 1.2°C; and 3) heat exposure + brachial artery compression to inhibit the temperature-dependent increase in shear stress. Endothelial function was assessed via brachial artery flow-mediated dilatation before (pre-I/R) and after (post-I/R) 20 min of arm ischemia followed by 20 min of reperfusion. Brachial artery shear rate was increased during heat exposure (681 ± 359 s-1), but not for thermoneutral control (140 ± 63 s-1; P < 0.01 vs. heat exposure) nor for heat + brachial artery compression (139 ± 60 s-1; P < 0.01 vs. heat exposure). Ischemia-reperfusion injury reduced flow-mediated dilatation following thermoneutral control (pre-I/R, 5.5 ± 2.9% vs. post-I/R, 3.8 ± 2.9%; P = 0.06), but was protected following heat exposure (pre-I/R, 5.8 ± 2.9% vs. post-I/R, 6.1 ± 2.9%; P = 0.5) and heat + arterial compression (pre-I/R, 4.4 ± 2.8% vs. post-I/R, 5.8 ± 2.8%; P = 0.1). Contrary to our hypothesis, our findings demonstrate that shear stress induced by acute heat exposure is not obligatory to protect against endothelial I/R injury in humans.NEW & NOTEWORTHY Acute heat exposure protects against endothelial ischemia-reperfusion injury in humans. However, the mechanism/s mediating this protective effect remain unclear. We utilized arterial compression to inhibit the temperature-dependent increase in brachial artery blood velocity that occurs during acute heat exposure to isolate the contribution of shear stress to the protection of endothelial function following ischemia-reperfusion injury. Our findings demonstrate that shear stress induced by acute heat exposure is not obligatory to protect against endothelial I/R injury.

Green Tea Extract Concurrent with an Oral Nutritional Supplement Acutely Enhances Muscle Microvascular Blood Flow without Altering Leg Glucose Uptake in Healthy Older Adults.

Postprandial macro- and microvascular blood flow and metabolic dysfunction manifest with advancing age, so vascular transmuting interventions are desirable. In this randomised, single-blind, placebo-controlled, crossover trial, we investigated the impact of the acute administration of green tea extract (GTE; containing ~500 mg epigallocatechin-3-gallate) versus placebo (CON), alongside an oral nutritional supplement (ONS), on muscle macro- and microvascular, cerebral macrovascular (via ultrasound) and leg glucose/insulin metabolic responses (via arterialised/venous blood samples) in twelve healthy older adults (42% male, 74 ± 1 y). GTE increased m. vastus lateralis microvascular blood volume (MBV) at 180 and 240 min after ONS (baseline: 1.0 vs. 180 min: 1.11 ± 0.02 vs. 240 min: 1.08 ± 0.04, both p < 0.005), with MBV significantly higher than CON at 180 min (p < 0.05). Neither the ONS nor the GTE impacted m. tibialis anterior perfusion (p > 0.05). Leg blood flow and vascular conductance increased, and vascular resistance decreased similarly in both conditions (p < 0.05). Small non-significant increases in brachial artery flow-mediated dilation were observed in the GTE only and middle cerebral artery blood flow did not change in response to GTE or CON (p > 0.05). Glucose uptake increased with the GTE only (0 min: 0.03 ± 0.01 vs. 35 min: 0.11 ± 0.02 mmol/min/leg, p = 0.007); however, glucose area under the curve and insulin kinetics were similar between conditions (p > 0.05). Acute GTE supplementation enhances MBV beyond the effects of an oral mixed meal, but this improved perfusion does not translate to increased leg muscle glucose uptake in healthy older adults.

Brachial and carotid hemodynamic response to hot water immersion in men and women.

This study sought to compare the brachial and carotid hemodynamic response to hot water immersion (HWI) between healthy young men and women. Ten women (W) and 11 men (M) (24 ± 4 yr) completed a 60-min HWI session immersed to the level of the sternum in 40°C water. Brachial and carotid artery hemodynamics (Doppler ultrasound) were measured at baseline (seated rest) and every 15 min throughout HWI. Within the brachial artery, total shear rate was elevated to a greater extent in women [+479 (+364, +594) s-1] than in men [+292 (+222, +361) s-1] during HWI (P = 0.005). As shear rate is inversely proportional to blood vessel diameter and directly proportional to blood flow velocity, the sex difference in brachial shear response to HWI was the result of a smaller brachial diameter among women at baseline (P < 0.0001) and throughout HWI (main effect of sex, P < 0.0001) and a greater increase in brachial velocity seen in women [+48 (+36, +61) cm/s] compared with men [+35 (+27, +43) cm/s] with HWI (P = 0.047) which allowed for a similar increase in brachial blood flow between sexes [M: +369 (+287, +451) mL/min, W: +364 (+243, +486) mL/min, P = 0.943]. In contrast, no differences were seen between sexes in carotid total shear rate, flow, velocity, or diameter at baseline or throughout HWI. These data indicate the presence of an artery-specific sex difference in the hemodynamic response to a single bout of HWI.

The Effect of Magnesium Supplementation on Endothelial Function: A Randomised Cross-Over Pilot Study.

Evidence supports an association between low magnesium (Mg) intake and coronary heart disease and between Mg intake and endothelial function. The aim of this study was to assess the effect of one week of Mg supplementation on endothelial function, assessed by flow mediated dilatation (FMD). Nineteen healthy men and women completed this cross-over pilot study in which participants were randomised to take an over-the-counter magnesium supplement for one week or to follow their usual diet. Weight, FMD and blood pressure (BP) were taken on completion of each intervention and 24 h urine collections and blood samples were taken to assess compliance. Baseline serum Mg was within normal range for all participants. Urinary Mg and urinary magnesium-creatinine ratio (Mg/Cr) significantly increased between interventions, (p = 0.03, p = 0.005, respectively). No significant differences in FMD or BP were found between the interventions. A significant negative correlation was seen between age and FMD (r = -0.496, p = 0.031). When adjusted for age, saturated fat was negatively associated with FMD (p = 0.045). One week of Mg supplementation did not improve FMD in a healthy population.

The Acute Effect of Magnesium Supplementation on Endothelial Function: A Randomized Cross-Over Pilot Study.

Magnesium (Mg) deficiency might be a catalyst in the process of endothelial dysfunction, an early event in the pathogenesis of atherosclerosis. The aim of this study was to determine the acute effect of an oral Mg supplement as compared to control on endothelial function assessed by flow-mediated dilatation (FMD). Nineteen participants (39 years, body mass index (BMI) 22.9 kg/m2) completed this randomized cross-over study. Blood pressure (BP) and FMD were measured and blood samples were taken before participants drank 200 mL water, with or without an over the counter Mg supplement (450 mg and 300 mg for men and women). Measurements were repeated at 60 and 120 min. There was a statistically significant two-way interaction between treatment and time on serum Mg (p = 0.037). A difference of -0.085 mm in FMD was observed 60-min post drink in the control group, as compared to baseline FMD, and no difference was observed in the supplement group as compared to baseline. Despite the non-significant interaction between treatment and time on FMD, once adjusted for baseline, the difference seen in the control group and the lack of change in the supplement group at 60 min post-drink suggests that Mg might attenuate the reduction in FMD post-prandially.

Improvements in vascular function in response to acute lower limb heating in young healthy males and females.

Regular exposure to passive heat stress improves vascular function, but the optimal heating prescription remains undefined. Local limb heating is more feasible than whole body heating, but the evidence demonstrating its efficacy is lacking. The purpose of this study was to determine whether acute improvements in vascular function can be achieved with lower limb heating in 16 young healthy individuals (8 female, 8 male). In separate visits, participants underwent 45 min of ankle- and knee-level hot water immersion (45°C). A subset of seven participants also participated in a time-control visit. Endothelial function was assessed through simultaneous brachial and superficial femoral artery flow-mediated dilation (FMD) tests. Macrovascular function was quantified by %FMD, whereas microvascular function was quantified by vascular conductance during reactive hyperemia. Arterial stiffness was assessed through carotid-femoral and femoral-foot pulse wave velocity (PWV). Plasma concentrations of interleukin-6 and extracellular heat shock protein-72 (eHSP72) were used as indicators of inflammation. Our findings showed that 45 min of lower limb heating-regardless of condition-acutely improved upper limb macrovascular endothelial function (i.e., brachial %FMD; Pre: 4.6 ± 1.7 vs. Post: 5.4 ± 2.0%; P = 0.004) and lower limb arterial stiffness (i.e., femoral-foot PWV; Pre: 8.4 ± 1.2 vs. Post: 7.7 ± 1.1 m/s; P = 0.011). However, only knee-level heating increased upper limb microvascular function (i.e., brachial peak vascular conductance; Pre: 6.3 ± 2.7 vs. Post: 7.8 ± 3.5 mL/min â‹… mmHg; P ≤ 0.050) and plasma eHSP72 concentration (Pre: 12.4 ± 9.4 vs. Post: 14.8 ± 9.8 ng/mL; P ≤ 0.050). These findings show that local lower limb heating acutely improves vascular function in younger individuals, with knee-level heating improving more outcome measures.NEW & NOTEWORTHY This study demonstrates that lower limb hot water immersion is an effective strategy for acutely improving vascular function in young, healthy males and females, thereby encouraging the development of accessible modes of heat therapy for vascular health.

Postprandial Fatty Acid Profile, but Not Cardiometabolic Risk Markers, Is Modulated by Dairy Fat Manipulation in Adults with Moderate Cardiovascular Disease Risk: The Randomized Controlled REplacement of SaturatEd fat in dairy on Total cholesterol (RESET) Study.

BACKGROUND: Chronic consumption of dairy products with an SFA-reduced, MUFA-enriched content was shown to impact favorably on brachial artery flow-mediated dilatation (FMD). However, their acute effect on postprandial cardiometabolic risk biomarkers requires investigation. OBJECTIVE: The effects of sequential high-fat mixed meals rich in fatty acid (FA)-modified or conventional (control) dairy products on postprandial FMD (primary outcome) and systemic cardiometabolic biomarkers in adults with moderate cardiovascular risk (≥50% above the population mean) were compared. METHODS: In a randomized crossover trial, 52 participants [mean ± SEM age: 53 ± 2 y; BMI (kg/m2) 25.9 ± 0.5] consumed a high-dairy-fat breakfast (0 min; ∼50 g total fat: modified: 25 g SFAs, 20 g MUFAs; control: 32 g SFAs, 12 g MUFAs) and lunch (330 min; ∼30 g total fat; modified: 15 g SFAs, 12 g MUFAs; control: 19 g SFAs, 7 g MUFAs). Blood samples were obtained before and until 480 min after breakfast, with FMD assessed at 0, 180, 300, and 420 min. Data were analyzed by linear mixed models. RESULTS: Postprandial changes in cardiometabolic biomarkers were comparable between the different dairy meals, with the exception of a tendency for a 4% higher AUC for the %FMD response following the modified-dairy-fat meals (P = 0.075). Plasma total lipid FA analysis revealed that incremental AUC responses were 53% lower for total SFAs, 214% and 258% higher for total cis-MUFAs (predominantly cis-9 18:1), and trans-18:1, respectively, following the modified relative to the control dairy meals (all P < 0.0001). CONCLUSIONS: In adults at moderate cardiovascular risk, acute consumption of sequential high-fat meals containing FA-modified dairy products had little impact on postprandial endothelial function or systemic cardiometabolic biomarkers, but a differential effect on the plasma total lipid FA profile, relative to conventional dairy fat meals.This trial was registered at clinicaltrials.gov as NCT02089035.

Lactobacillus plantarum 299v probiotic supplementation in men with stable coronary artery disease suppresses systemic inflammation.

Recent trials demonstrate that systemic anti-inflammatory therapy reduces cardiovascular events in coronary artery disease (CAD) patients. We recently demonstrated Lactobacillus plantarum 299v (Lp299v) supplementation improved vascular endothelial function in men with stable CAD. Whether this favorable effect is in part due to anti-inflammatory action remains unknown. Testing this hypothesis, we exposed plasma obtained before and after Lp299v supplementation from these subjects to a healthy donor's PBMCs and measured differences in the PBMC transciptome, performed gene ontological analyses, and compared Lp299v-induced transcriptome changes with changes in vascular function. Daily alcohol users (DAUs) (n = 4) had a significantly different response to Lp299v and were separated from the main analyses. Non-DAUs- (n = 15) showed improved brachial flow-mediated dilation (FMD) and reduced circulating IL-8, IL-12, and leptin. 997 genes were significantly changed. I.I.com decreased (1.01 ± 0.74 vs. 0.22 ± 0.51; P < 0.0001), indicating strong anti-inflammatory effects. Pathway analyses revealed downregulation of IL-1ß, interferon-stimulated pathways, and toll-like receptor signaling, and an increase in regulator T-cell (Treg) activity. Reductions in GBP1, JAK2, and TRAIL expression correlated with improved FMD. In non-DAU men with stable CAD, post-Lp299v supplementation plasma induced anti-inflammatory transcriptome changes in human PBMCs that could benefit CAD patients. Future studies should delineate changes in circulating metabolites responsible for these effects.

Inorganic nitrate supplementation attenuates conduit artery retrograde and oscillatory shear in older adults.

Aging causes deleterious changes in resting conduit artery shear patterns and reduced blood flow during exercise partially attributable to reduced nitric oxide (NO). Inorganic nitrate increases circulating NO bioavailability and may, therefore, improve age-associated changes in shear rate as well as exercise hyperemia. Ten older adults (age: 67 ± 3 yr) consumed 4.03 mmol nitrate and 0.29 mmol nitrite (active) or devoid of both (placebo) daily for 4 wk in a randomized, double-blinded, crossover fashion. Brachial artery diameter (D) and blood velocity (Vmean) were measured via Doppler ultrasound at rest for the characterization of shear profile as well as during two handgrip exercise trials (4 and 8 kg) for calculation of forearm blood flow (Vmean × cross-sectional area, FBF) and conductance [FBF/mean arterial pressure, forearm vascular conductance (FVC)]. Plasma [nitrate] and [nitrite] increased following active (P < 0.05 for both) but not placebo (P = 0.68 and 0.40, respectively) supplementation. Neither mean nor antegrade shear rate changed following either supplement (beverage-by-time P = 0.14 and 0.21, respectively). Retrograde (-13.4 ± 7.0 to -9.7 ± 6.8·s-1) and oscillatory (0.20 ± 0.08 to 0.15 ± 0.09 A.U., P < 0.05 for both) shear decreased following active, but not placebo (P = 0.81 and 0.70, respectively), supplementation. The FBF response (Δ from rest) to neither 4-kg nor 8-kg trials changed following either supplement (beverage-by-time P = 0.53 and 0.11, respectively). Similarly, no changes were observed in FVC responses to 4-kg or 8-kg trials (beverage-by-time P = 0.23 and 0.07, respectively). These data indicate that inorganic nitrate supplementation improves conduit artery shear profiles, but not exercise hyperemia, in older adults.NEW & NOTEWORTHY We report for the first time, to our knowledge, that 4 wk of inorganic nitrate supplementation attenuates retrograde and oscillatory shear in the brachial artery of older adults. However, this was not associated with greater hyperemic or vasodilatory responses to exercise. In sum, these data highlight favorable changes in shear patterns with aging, which may reduce the risk of atherosclerotic cardiovascular disease.

Distinct contributions of skin and core temperatures to flow-mediated dilation of the brachial artery following passive heating.

We measured acute vascular responses to heat stress to examine the hypothesis that macrovascular endothelial-dependent dilation is improved in a shear-dependent manner, which is further modified by skin temperature. Twelve healthy males performed whole body heating (+1.3°C esophageal temperature), bilateral forearm heating (∼38°C skin temperature), and a time-matched (∼60 min) control condition on separate days in a counterbalanced order. Bilateral assessments of blood flow and brachial artery flow-mediated dilation (FMD) were performed before and 10 min after each condition with duplex Doppler ultrasound. To isolate the influence of shear stress, a pneumatic cuff was inflated (∼90 mmHg) around the right forearm during each condition to attenuate heat-induced rises in blood flow and shear stress. After forearm heating, FMD increased [cuffed: 4.7 (2.9)% to 6.8 (1.5)% and noncuffed: 5.1 (2.8)% to 6.4 (2.6)%] in both arms (time P < 0.01). Whole body heating also increased FMD in the noncuffed arm from 3.6 (2.2)% to 9.2 (3.2)% and in the cuffed arm from to 5.6 (3.0)% to 8.6 (4.9)% (time P < 0.01). After the time control, FMD decreased [cuffed: 6.3 (2.4)% to 4.7 (2.2)% and noncuffed: 6.1 (3.0)% to 4.5 (2.6)%] in both arms (time P = 0.03). Multiple linear regression (adjusted R2 = 0.421 P = 0.003) revealed that changes in esophageal temperature, skin temperatures, and heart rate explained the majority of the variance in this model (34%, 31%, and 21%, respectively). Our findings indicate that, in addition to shear stress, skin and core temperatures are likely important contributors to passive heating-induced vascular adaptations.NEW & NOTEWORTHY The primary determinant of vascular adaptations to lifestyle interventions, such as exercise and heat therapy, is repeated elevations in vascular shear stress. Whether skin or core temperatures also modulate the vascular adaptation to acute heat exposure is unknown, likely due to difficulty in dissociating the thermal and hemodynamic responses to heat. We found that skin and core temperatures modify the acute vascular responses to passive heating irrespective of the magnitude of increase in shear stress.