Endothelial Function In Healthy Men Research Articles

Effects of repetition exercise training on vascular endothelial function in healthy men

Effects of repetition exercise training on vascular endothelial function in healthy men

The comparison of endothelial function of moderate intensity interval exercise with continuous exercise in healthy men.

Background/aimExercise enhances endothelium-dependent vasodilation; however, it is unclear whether intermittent exercise has a different effect on vascular endothelial function compared to continuous exercise. This study aimed to compare vascular endothelial function following intermittent exercise including short rest intervals with continuous exercise, both at the anaerobic threshold level.Materials and methodsPeak oxygen consumption (VO2 peak) and anaerobic threshold were measured in physically active healthy young men (n = 12) by breath-by-breath analysis. After completion of intermittent exercise consisting of eight 1-min long intervals at the anaerobic threshold intensity with 75-s rest periods, total work was calculated. Equivalent work was done during continuous exercise. Immediately after the two exercise periods, venous blood lactate, endothelial nitric oxide synthase (eNOS), endothelin-1, N-terminal proANP (NTproANP), N-terminal proBNP (NTproBNP), and N-terminal proCNP (NTproCNP) levels were measured. Brachial artery flow-mediated dilatation (FMD) was measured before exercise and 30 min after exercise.ResultsMean VO2 peak level was 33.42 ± 5.9 ml/min/kg and anaerobic threshold level was 47.33 ± 5.85%. Lactate levels following continuous exercise were higher than levels following intermittent exercise (27.76 ± 7.43 mg/dl, 18.54 ± 4.87 mg/dl respectively; p˂0.05). Endothelin-1, eNOS, NTproANP, NTproBNP, and NTproCNP levels were similar after both modalities of exercise (p > 0.05). No significant difference was found in FMD response when comparing intermittent and continuous exercise (7.05 ± 15.11%, 2.49 ± 16.24% respectively; p > 0.05).ConclusionSince blood lactate levels are higher following continuous exercise, individuals who find difficulty exercising may prefer an intermittent form of exercise. However, both intermittent and continuous exercise at the anaerobic threshold level seem to not produce a significant acute change in endothelial function in healthy men.

Exercise modality, but not exercise training, alters the acute effect of exercise on endothelial function in healthy men.

We used a within-subject crossover design to examine the impact of exercise modality, i.e., resistance (RT) and endurance (END), on the acute impact of exercise on endothelial function. Then, we examined whether a 4-wk period of chronic exercise training altered the acute exercise-induced change in endothelial function in healthy individuals. Thirty-four healthy, young men (21 ± 2 yr) reported to our laboratory and completed assessment of endothelial function [using the brachial artery flow-mediated dilation test (FMD)] before and immediately after a single bout of RT (leg-extension) or END (cycling). Subsequently, participants completed a 4-wk period of training (12 sessions), followed by evaluation of the FMD before and after a single bout of exercise. Following a 3-wk washout, participants repeated these experiments with the different exercise modality (in a balanced crossover design). An exercise × modality interaction effect was found (P < 0.001). Post hoc pairwise analyses revealed a decrease in FMD after END (P < 0.001) but not after RT (P = 0.06). Four weeks of exercise training improved resting FMD after END and RT (P = 0.04) but did not alter the acute effect of exercise on FMD (exercise × modality × training effect: P = 0.63), an effect independent of the modality of exercise (exercise × training interaction: P = 0.46 and P = 0.11 in RT and END, respectively). These distinct changes in FMD following acute exercise may relate to the different prolonged physiological responses induced by endurance versus resistance exercise. Specifically, endurance exercise, but not resistance exercise, causes a decrease in brachial artery endothelial function, which was unaffected by 4 wk of chronic exercise training.NEW & NOTEWORTHY We found that resistance and endurance exercise modalities lead to different endothelial function responses after a single bout of exercise. Endothelial function increased after an acute bout of resistance exercise, whereas it decreased after an acute bout of endurance exercise. Four weeks of chronic exercise training did not affect the acute endothelial function response.

The influence of acute hyperglycaemia on brachial artery flow-mediated dilatation in the early and late follicular phases of the menstrual cycle.

What is the central question of the study? This is the first study to examine the impact of acute hyperglycaemia on endothelial function [flow-mediated dilatation (FMD)] in premenopausal women across the early and late follicular (EF and LF) phases of the menstrual cycle. What is the main finding and its importance? Flow-mediated dilatation was impaired 90 min after glucose ingestion, with no significant difference between phases. This indicates that women are susceptible to acute hyperglycaemia-induced endothelial dysfunction in both the EF and LF phases of the menstrual cycle, despite potentially vasoprotective elevations in estradiol levels during the LF phase. Acute hyperglycaemia transiently impairs endothelial function in healthy men when assessed via flow-mediated dilatation (FMD). However, research in female participants is lacking, and the impact of menstrual phase [early follicular (EF) and late follicular (LF)] on vulnerability to acute hyperglycaemia-induced endothelial dysfunction is unknown. Seventeen healthy, naturally menstruating women [21±1 years old (mean ± SD)] participated in three visits. During two visits (EFGlucose and LFGlucose ), brachial artery FMD was assessed before and 60, 90 and 120min after an oral glucose challenge (75g glucose). During an additional EF visit, participants ingested 300ml of water (EFTimeControl ). Blood glucose and insulin increased 30 min after glucose ingestion (P<0.001), with no difference between phases. Flow-mediated dilatation did not change in EFTimeControl (P=0.748) but was reduced 90min after glucose ingestion (Pre, 8.5±2.5%; Post90, 6.6±2.4%, P=0.001; Cohen's d=0.82), with no difference between phases (main effect of phase, P=0.506; phase by time interaction, P=0.391). To account for individual variability in the time course of the impact of hyperglycaemia, the maximal hyperglycaemia-induced impairment in FMD was determined in each participant and compared between phases, revealing no significant phase differences (EFGlucose , -3.1±2.8%; LFGlucose , -2.4±2.1%, P=0.181; d=0.34). These results indicate that, similar to findings in men, acute hyperglycaemia results in FMD impairment in young women. We did not detect significant protection from acute hyperglycaemia-induced endothelial dysfunction in the LF 'high-oestrogen' phase in this sample, and further research is needed to examine the potential for a protective effect of oestrogen exposure, including oral contraceptive pills and hormone replacement therapy.

Brachial artery endothelial function is unchanged after acute sprint interval exercise in sedentary men and women.

What is the central question of this study? What is the acute brachial artery endothelial function response to sprint interval exercise and are there sex-based differences? What is the main finding and its importance? Brachial artery endothelial function did not change in either men or women following an acute session of SIT consisting of 3×20s 'all-out' cycling sprints. Our findings suggest this low-volume protocol may not be sufficient to induce functional changes in the brachial artery of sedentary, but otherwise healthy adults. Sprint interval training (SIT) is a potent metabolic stimulus, but studies examining its acute effects on brachial artery endothelial function are limited. The influence of oestradiol on the acute arterial response to this type of exercise is also unknown. We investigated the brachial artery endothelial function response to a single session of SIT in sedentary healthy men (n=8; 22±4years) and premenopausal women tested in the mid-follicular phase of the menstrual cycle (n=8; 21±3years). Participants performed 3×20s 'all-out' cycling sprints interspersed with 2min of active recovery. Brachial artery flow-mediated dilatation (FMD) and haemodynamic parameters were measured before and 1 and 24h post-exercise. Despite attenuations in some haemodynamic parameters at 1 h post-exercise, there were no changes in absolute (P=0.23), relative (P=0.23) or allometrically scaled FMD (P=0.38) following a single session of SIT. Resting and peak dilatory diameters did not change in men or women (P>0.05 for all) and there were no interactions between time and sex for any measure (P>0.05). Oestradiol was not correlated with relative FMD at baseline (r=-0.22, P=0.42) or with the change in relative FMD from baseline to 1h post-exercise (r=0.24, P=0.40). Overall, brachial artery FMD appears to be unchanged in men and women following an acute session of SIT, and the higher oestradiol concentrations in women do not augment the baseline or post-exercise FMD response. The 3×20s model of low-volume sprint interval exercise may not be sufficient to alter brachial artery endothelial function in healthy men and women.

Non-Smoking Tobacco Affects Endothelial Function in Healthy Men in One of the Largest Health Studies Ever Performed; The Nord-Trøndelag Health Study in Norway; HUNT3.

BackgroundOral tobacco (snuff) is taking a large market share in Scandinavia, especially with young users. However, long-term health effects are unknown. Small studies show association between snuff and reduced endothelial function, representing an early stage of vascular injury that often precedes manifest cardiovascular disease by several years. We therefore determined the associations between snuff and endothelial function in a large sample of healthy Norwegian men.Methods and DesignIn the Fitness substudy of the Nord-Trøndelag Health Study (HUNT3), endothelial function was measured by flow-mediated dilation (FMD). Aerobic fitness was measured by peak oxygen uptake (VO2peak). A cross-sectional design including 1 592 self-reported healthy men compared these observations with records of present tobacco use, standard cardiovascular risk factors, and socioeconomic status, using general linear models.ResultsFMD was lower in snuff users (FMD: 4.12%, 3.63, 4.61) compared to non-users (FMD: 4.52%, 4.27, 4.78) after adjustment for age (difference: -0.57%, -1.12, -0.01). After further adjustment for potential confounders, FMD still tended to be lower in snuff users than in non-users (difference: -0.53%, -1.09, 0.02). This difference was even more pronounced in the inactive snuff users (-0.83%, -1.59, -0.06) and in the low fit snuff users (-0.74%, CI -0.55, 0.079).ConclusionsOral tobacco is associated with a tendency towards reduced endothelial function, indicating vascular changes that precede cardiovascular disease. The strongest associations were found in men with low physical activity or reduced aerobic fitness.

Intake and time dependence of blueberry flavonoid–induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity

There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans. We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity. Two randomized, controlled, double-blind, crossover human-intervention trials were conducted with 21 healthy men. Initially, the impact of blueberry flavonoid intake on flow-mediated dilation (FMD) and polyphenol absorption and metabolism was assessed at baseline and 1, 2, 4, and 6 h after consumption of blueberry containing 766, 1278, and 1791 mg total blueberry polyphenols or a macronutrient- and micronutrient-matched control drink (0 mg total blueberry polyphenols). Second, an intake-dependence study was conducted (from baseline to 1 h) with 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols and a control. We observed a biphasic time-dependent increase in FMD, with significant increases at 1-2 and 6 h after consumption of blueberry polyphenols. No significant intake-dependence was observed between 766 and 1791 mg. However, at 1 h after consumption, FMD increased dose dependently to ≤766 mg total blueberry polyphenol intake, after which FMD plateaued. Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1-2 and 6 h. Blueberry intake acutely improves vascular function in healthy men in a time- and intake-dependent manner. These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity. This trial was registered at clinicaltrials.gov as NCT01292954 and NCT01829542.

Wolfgang Kiowski

Wolfgang Kiowski

Postprandial Hyperglycemia Impairs Vascular Endothelial Function in HealthyMen by Inducing Lipid Peroxidation and Increasing Asymmetric Dimethylarginine:Arginine

Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and increases future cardiovascular disease risk. We hypothesized that postprandial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n= 16; 21.6 ± 0.8 y) ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA were measured at regular intervals during the 3-h postprandial period. Baseline FMD did not differ between trials (P> 0.05). Postprandial FMD was reduced following the ingestion of glucose only. Postprandial MDA concentrations increased to a greater extent following the ingestion of glucose compared to fructose. Plasma arginine decreased and the ratio of ADMA:arginine increased to a greater extent following the ingestion of glucose. Inflammatory cytokines and cellular adhesion molecules were unaffected by the ingestion of either sugar. Postprandial AUC0–3 hfor FMD and MDA were inversely related (r= -0.80;P< 0.05), suggesting that hyperglycemia-induced lipid peroxidation suppresses postprandial vascular function. Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation. Postprandial alterations in arginine and ADMA:arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stress-dependent mechanism. Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function.

Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial

Flavonoids and nitrates in fruits and vegetables may protect against cardiovascular disease. Dietary flavonoids and nitrates can augment nitric oxide status via distinct pathways, which may improve endothelial function and lower blood pressure. Recent studies suggest that the combination of flavonoids and nitrates can enhance nitric oxide production in the stomach. Their combined effect in the circulation is unclear. Here, our objective was to investigate the independent and additive effects of flavonoid-rich apples and nitrate-rich spinach on nitric oxide status, endothelial function, and blood pressure. A randomized, controlled, crossover trial with healthy men and women (n=30) was conducted. The acute effects of four energy-matched treatments (control, apple, spinach, and apple+spinach), administered in random order, were compared. Measurements included plasma nitric oxide status, assessed by measuring S-nitrosothiols+other nitrosylated species (RXNO) and nitrite, blood pressure, and endothelial function, measured as flow-mediated dilatation of the brachial artery. Results are means and 95% CI. Relative to control, all treatments resulted in higher RXNO (control, 33nmol/L, 26, 42; apple, 51nmol/L, 40, 65; spinach, 86nmol/L, 68, 110; apple+spinach, 69nmol/L, 54, 88; P<0.01) and higher nitrite (control, 35nmol/L, 27, 46; apple, 69nmol/L, 53, 90; spinach, 99nmol/L, 76, 129; apple+spinach, 80nmol/L, 61, 104; P<0.01). Compared to control, all treatments resulted in higher flow-mediated dilatation (P<0.05) and lower pulse pressure (P<0.05), and apple and spinach resulted in lower systolic blood pressure (P<0.05). No significant effect was observed on diastolic blood pressure. The combination of apple and spinach did not result in additive effects on nitric oxide status, endothelial function, or blood pressure. In conclusion, flavonoid-rich apples and nitrate-rich spinach can independently augment nitric oxide status, enhance endothelial function, and lower blood pressure acutely, outcomes that may benefit cardiovascular health.

Effects of lycopene supplementation on oxidative stress and markers of endothelial function in healthy men

ObjectiveThe objective was to determine the effects of lycopene supplementation on endothelial function assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT) and oxidative stress. MethodsHealthy men (n=126) were randomized to receive placebo (n=38), 6mg (n=41), or 15mg (n=37) lycopene daily for 8-week. ResultsSerum lycopene increased in a dose-dependent manner after 8-week supplementation (P<0.001). The 15mg/day group had greater increase in plasma SOD activity (P=0.014) and reduction in lymphocyte DNA comet tail length (P=0.042) than the placebo group. Intragroup comparison revealed a 23% increase in RH-PAT index from baseline (1.45±0.09 vs. 1.79±0.12; P=0.032) in the 15mg/day group after 8-week. hs-CRP, systolic blood pressure, sICAM-1 and sVCAM-1 significantly decreased, and β-carotene and LDL-particle size significantly increased only in the 15mg/day group. Interestingly, the beneficial effect of lycopene supplementation on endothelial function (i.e., RH-PAT and sVCAM-1) were remarkable in subjects with relatively impaired endothelial cell function at initial level. Changes in RH-PAT index correlated with SOD activity (r=0.234, P=0.017) especially in the 15mg lycopene/day group (r=0.485, P=0.003), lymphocyte DNA comet tail moment (r=−0.318, P=0.001), and hs-CRP (r=−0.238, P=0.011). In addition, changes in lycopene correlated with hs-CRP (r=−0.230, P=0.016) and SOD activity (r=0.205, P=0.037). ConclusionAn increase in serum lycopene after supplementation can reduce oxidative stress which may play a role in endothelial function.

Rapid effect of single-dose rosiglitazone treatment on endothelial function in healthy men with normal glucose tolerance: data from a randomised, placebo-controlled, double-blind study

Antidiabetic thiazolidinediones (TZDs) improve endothelial function in patients with or without type 2 diabetes. The present randomised, placebo-controlled, double-blind study examined the time course of a single dose of rosiglitazone on flow-mediated endothelium-dependent vasodilation (FMD), metabolic parameters, and its effect on inflammatory markers in non-diabetic men. Forty non-obese, healthy men with normal glucose tolerance were randomised to a single dose of rosiglitazone (8 mg) or placebo, and FMD was assessed at baseline as well as after 6 h and 24 h. Rosiglitazone did not significantly affect blood glucose and insulin levels or lipid parameters after 6 and 24 h compared with placebo. Treatment with rosiglitazone significantly increased FMD after 6 h from 4.3% (3.3; 4.9) to 7.6% (5.6; 9.2) (p<0.0001 vs. baseline) resulting in a highly significant effect compared with placebo (p<0.0001 for difference between groups). After 24 h FMD was still significantly higher in the rosiglitazone group compared with baseline (p=0.001), but the effect was no longer statistically significant versus placebo (p=0.171). Our study shows a very rapid effect of single dose rosiglitazone treatment on endothelial function in non-diabetic healthy men, underscoring the hypothesis that TZDs may exhibit direct effect in the vasculature independent of their metabolic action.

Variability of Peripheral Arterial Tonometry in the Measurement of Endothelial Function in Healthy Men

Measurement of endothelial function using peripheral arterial tonometry (PAT) has been reported to be significantly correlated with coronary blood flow. Repetitive PAT measurements were performed in 22 healthy male subjects at test intervals of 1 hour (5 times within a day) and 0.5 hours (7 times within a day) to evaluate the variability of the reactive hyperemia index (RHI). A total of 10 subjects underwent additional repetitive PAT at 2 hour intervals (7 times within a day) for 3 consecutive days to evaluate the diurnal effects and day-to-day reproducibility. The RHI from each test was computed automatically based on a 15 minute recording of pulse wave amplitude changes of the fingers in response to reactive hyperemia induced by a 5 minute occlusion of the brachial artery. Intrasubject variability of RHI at different test intervals, defined as the coefficient of variation (CV) was 15.3% +/- 5.3%, 16.1%+/- 7.8%, and 22.6% +/- 3.9% for the tests at 0.5 hour, 1 hour, and 2 hour intervals, respectively. Reactive hyperemia indices measured at the same time points on each of the 3 days were not statistically significant. The interday reproducibility, presented as intraclass correlation coefficients (ICC) ranged from - 0.07 to 0.47. We conclude that repetitive PAT measurements have no carryover effect on RHI at 1 hour, and 2 hour intervals, and the RHI measured at 0.5 hour intervals is associated with a trend of increase. The interday reproducibility is relatively low and the intrasubject variability of RHI is similar to those observed in studies of flow-mediated dilation using brachial artery ultrasound scanning.

Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with α-linolenic acid on postprandial endothelial function in healthy men

Traditional cardiovascular risk factors are associated with endothelial dysfunction. The vascular endothelium plays a key role in local vascular tone regulation and can be modulated by dietary fat. We propose to determine the chronic effect of three diets with different fat compositions on postprandial endothelial function and inflammatory biomarkers. Twenty healthy men followed three 4-week diets in a randomised cross-over design: a Western diet, rich in saturated fat (22% SFA, 12% MUFA and 0.4% alpha-linolenic acid (ALA), all fractions are % of energy); a Mediterranean diet, rich in MUFA ( < 10 % SFA, 24 % MUFA and 0.4% ALA); a low-fat diet enriched in ALA ( < 10% SFA, 12% MUFA and 2% ALA). At the end of each dietary period all subjects underwent a postprandial study. Plasma concentrations of lipid parameters, soluble intercellular cell-adhesion molecule-1, soluble vascular cell-adhesion molecule-1 (sVCAM-1), nitrates and nitrites (NOx) and endothelial function studied by laser Doppler were examined at 0, 2, 4, 6 and 8 h. The endothelium-dependent vasodilatory response was greater 4 h after the ingestion of the MUFA-rich diet than after the SFA or ALA low-fat diets (P = 0.031). The 4 h postprandial plasma sVCAM-1 levels were lower after the MUFA meals than after the ALA low-fat diet (P = 0.043). The bioavailability of NOx was higher following the MUFA diet than after the SFA and ALA low-fat diets (P = 0.027). We found no differences in the other parameters measured. Chronic ingestion of a Mediterranean diet avoids the postprandial deterioration of endothelial function associated with Westernised diets in healthy individuals.

Influence of Acute and Chronic Mineralocorticoid Excess on Endothelial Function in Healthy Men

Aldosterone has rapid nongenomic effects in the human vasculature. However, data are not uniform and little is known about chronic effects of aldosterone. Therefore, we investigated acute and chronic effects of elevated aldosterone levels on endothelial function in the forearm vasculature of healthy men. In a first crossover study, the effects of arterial aldosterone infusion in ascending doses (3.3 to 55 pmol/min per 1000 mL forearm volume) on forearm blood flow were investigated in 8 healthy men (26+/-2 years). In a second study, endothelium-dependent (acetylcholine; 0.08, 0.275, and 2.75 micromol/min per 1000 mL) and endothelium-independent (sodium nitroprusside 0.02 micromol/min per 1000 mL) vasodilation and basal nitric oxide formation (forearm blood flow response to blockade by N(G)-monomethyl-l-arginine 8 micromol/min per 1000 mL) were tested in 10 healthy men (age 30+/-5 years) at baseline, during infusion of 55 pmol/1000 mL per min aldosterone (acute effects), and after 0.3 mg/d oral fludrocortisone for 2 weeks (chronic effects) on separate days. Forearm blood flow was assessed by venous occlusion plethysmography. No change in forearm blood flow was seen with aldosterone infusion alone. Acute coinfusion of aldosterone increased vasodilation to sodium nitroprusside by 93% (P<0.01) and to acetylcholine by 60% (P=0.14). Response to N(G)-monomethyl-l-arginine did not change. After 2 weeks of oral fludrocortisone, response to acetylcholine was enhanced by 72% compared with baseline (P=0.03). Additionally, response to N(G)-monomethyl-l-arginine was enhanced by 80% compared with baseline (P=0.05). Aldosterone acutely enhances vasodilation to exogenous nitric oxide whereas mineralocorticoid excess for 2 weeks enhances basal nitric oxide bioactivity and improves endothelium dependent, nitric oxide-mediated vasodilation in the forearm vasculature of healthy men.

Moderate RED wine consumption improve endothelial function in healthy men

Moderate RED wine consumption improve endothelial function in healthy men