Aerobic run training improves brachial artery flow-mediated dilation

The purpose of this study was to assess the relationship between aerobic exercise training and brachial artery flow-mediated dilation (FMD) in healthy subjects. Healthy controls (HC) and aerobically-trained (T) subjects were studied with high-resolution vascular ultrasound at baseline, and during a 5-minute period of hyperemia following forearm cuff occlusion. Training was defined by self-reported participation in recreational or competitive run training. Forearm cuff occlusion was held at 200 mm Hg for 5 minutes. At baseline, both brachial artery flow and diameter were greater in T than in HC (p < 0.05). Resting heart rate was lower in T than in HC (p < 0.05). Peak hyperemic flow (15 seconds postocclusion) was significantly greater in T than in HC (HC; 539 +/- 75 ml x min(-1) vs. T; 832 +/- 103 ml x min(-1), p < 0.05) and correlated well with V(.-)O2peak (r = 0.67, p = 0.008). Flow-mediated dilation was significantly greater in T vs. HC throughout the 5-minute postocclusion phase (p < 0.05). Maximal brachial artery dilation was greater in T than in HC (HC; 3 +/- 1% of baseline vs. T; 8 +/- 3% of baseline; p < 0.05) and moderately correlated with V(.-)O2peak (r = 0.55, p < 0.05). These data suggest that the greater FMD observed in trained subjects may be due, in part, to an augmentation of peak hyperemic flow.     

Endothelial function in highly endurance-trained men: effects of acute exercise

Exercise training reverses endothelial dysfunction, but the effect in young, healthy subjects is less clear. We determined the influence of maximal oxygen uptake (VO2max) and a single bout of high-intensity exercise on flow-mediated dilatation (FMD), brachial artery diameter, peak blood flow, nitric oxide (NO) bioavailability, and antioxidant status in highly endurance-trained men and their sedentary counterparts. Ten men athletes (mean +/- SEM age 23.5 +/- 0.9 years, height 182.6 +/- 2.4 cm, weight 72.5 +/- 2.4 kg, VO2max 75.9 +/- 0.8 mL.kg.min) and seven healthy controls (age 25.4 +/- 1.2 years, height 183.9 +/- 3.74 cm, weight 92.8 +/- 3.9 kg, VO2max 47.7 +/- 1.7 mL.kg.min) took part in the study. FMD, brachial artery diameter, and peak blood flow were measured using echo-Doppler before, 1 hour, 24 hours, and 48 hours after a single bout of interval running for 5 x 5 minutes at 90% of maximal heart rate. NO bioavailability and antioxidant status in blood were measured at all time points. Maximal arterial diameter and peak flow were 10-15% (P < 0.02) and 28-35% (P < 0.02) larger, respectively, in athletes vs. controls at all time points, and similar FMD were observed, apart from a transient decay of FMD in athletes 1 hour post exercise. NO bioavailability increased significantly after exercise in both groups and decreased to baseline levels after 24 hours in controls but remained increased 80% and 93% above baseline 24 and 48 hours post exercise in athletes. Antioxidant status was equal in the two groups at baseline and increased by approximately 10% 1 hour post exercise, an effect that lasted for 24 hours. Athletes had larger arterial diameter but similar FMD as untrained subjects, i.e., athletes had larger capacity for blood transport compared with their untrained counterparts. The observed FMD, bioavailability of NO, and antioxidant status in blood were highly dependent on the time elapsed after the exercise session.     

The Effect of Exercise Intensity on Endothelial Function in Physically Inactive Lean and Obese Adults

Purpose

To examine the effects of exercise intensity on acute changes in endothelial function in lean and obese adults.

Methods

Sixteen lean (BMI <25, age 23±3 yr) and 10 obese (BMI >30, age 26±6 yr) physically inactive adults were studied during 3 randomized admissions [control (C, no exercise), moderate-intensity exercise (M, @ lactate threshold (LT)) and high-intensity exercise (H, midway between LT and VO₂peak) (30 min)]. Endothelial function was assessed by flow-mediated dilation (FMD) at baseline and 1, 2, and 4 h post-exercise.

Results

RM ANCOVA revealed significant main effects for group, time, and group x condition interaction (p<0.05). A diurnal increase in FMD was observed in lean but not obese subjects. Lean subjects exhibited greater increases in FMD than obese subjects (p = 0.0005). In the obese group a trend was observed for increases in FMD at 2- and 4-hr after M (p = 0.08). For lean subjects, FMD was significantly elevated at all time points after H. The increase in FMD after H in lean subjects (3.2±0.5%) was greater than after both C (1.7±0.4%, p = 0.015) and M (1.4±0.4%, p = 0.002). FMD responses of lean and obese subjects significantly differed after C and H, but not after M.

Conclusion

In lean young adults, high-intensity exercise acutely enhances endothelial function, while moderate-intensity exercise has no significant effect above that seen in the absence of exercise. The FMD response of obese adults is blunted compared to lean adults. Diurnal variation should be considered when examining the effects of acute exercise on FMD.     

The Acute Effects of Grape Polyphenols Supplementation on Endothelial Function in Adults: Meta-Analyses of Controlled Trials

Background

The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD).

Methods

Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157.

Results

Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion.

Conclusions

Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.     

Endothelium-dependent and -independent vasodilation of the superficial femoral artery in spinal cord-injured subjects

Extreme inactivity of the legs in spinal cord-injured (SCI) individuals does not result in an impairment of the superficial femoral artery flow-mediated dilation (FMD). To gain insight into the underlying mechanism, the present study examined nitric oxide (NO) responsiveness of vascular smooth muscles in controls and SCI subjects. In eight healthy men (34 +/- 13 yr) and six SCI subjects (37 +/- 10 yr), superficial femoral artery FMD response was assessed by echo Doppler. Subsequently, infusion of incremental dosages of sodium nitroprusside (SNP) was used to assess NO responsiveness. Peak diameter was examined on a second day after 13 min of arterial occlusion in combination with sublingual administration of nitroglycerine. Resting and peak superficial femoral artery diameter in SCI subjects were smaller than in controls (P < 0.001). The FMD response in controls (4.2 +/- 0.9%) was lower than in SCI subjects (8.2 +/- 0.9%, P < 0.001), but not after correcting for area under the curve for shear rate (P = 0.35). When expressed as relative change from baseline, SCI subjects demonstrate a significantly larger diameter increase compared with controls at each dose of SNP. However, when expressed as a relative increase within the range of diameter changes [baseline (0%) - peak diameter (100%)], both groups demonstrate similar changes in response to SNP. Changes in diameter during SNP infusion and FMD response are larger in SCI subjects compared with controls. When these results are corrected, superficial femoral artery FMD and NO sensitivity in SCI subjects are not different from those in controls. This illustrates the importance of appropriate data presentation and suggests that, subsequent to structural inward remodeling of conduit arteries as a consequence of extreme physical inactivity, arterial function is normalized.     

Postprandial Vascular Reactivity in Obese and Normal Weight Young Adults

As humans spend a significant amount of time in the postprandial state, we examined whether vascular reactivity (a key indicator of cardiovascular health) was different after a high‐fat meal in 11 obese (median BMI 46.4, age 32.1 ± 6.3 years, 7 men) and 11 normal weight (median BMI 22.6) age‐ and sex‐matched controls. At baseline and 1 and 3 h postmeal, blood pressure (BP), heart rate (HR), reactive hyperemia peripheral artery tonometry (RH‐PAT) index, radial augmentation index adjusted for HR (AIx75), brachial pulse wave velocity (PWV_b), glucose, insulin, total and high‐density lipoprotein (HDL) cholesterol, and triglycerides were measured. Brachial flow‐mediated dilatation (FMD) and, by venous plethysmography, resting and hyperemic forearm blood flows (FBFs) were measured at baseline and 3 h. At baseline, obese subjects had higher systolic BP, HR, resting FBF, insulin and equivalent FMD, RH‐PAT, hyperemic FBF, AIx75, PWV_b, glucose, total cholesterol, triglycerides, and lower HDL cholesterol. In obese and lean subjects, FMD at baseline and 3 h was not significantly different (6.2 ± 1.7 to 5.8 ± 4.3% for obese and 4.7 ± 4.1 to 4.3 ± 3.9% for normal weight, P = 0.975 for group × time). The meal did not produce significant changes in RH‐PAT, hyperemic FBF, and PWV_b in either group (P > 0.1 for the effect of time and for group × time interactions). In conclusion, the vascular responses to a high‐fat meal are similar in obese and normal weight young adults. An exaggerated alteration in postprandial vascular reactivity is thus unlikely to contribute importantly to the increased cardiovascular risk of obesity.     

Improved analysis of brachial artery ultrasound using a novel edge-detection software system.

Brachial artery ultrasound is commonly employed for noninvasive assessment of endothelial function. However, analysis is observer dependent and susceptible to errors. We describe studies on a computerized edge-detection and wall-tracking software program to allow more accurate and reproducible measurement. In study 1, three purpose-built Perspex phantom arteries, 3.00, 4.00, and 6.00 mm in diameter, were measured with the software. There was a mean bias of 11 microm (P < 0.001 at each level) between known and measured values; the mean resolving power of the software was estimated as 8.3 microm. In study 2, the mean intraobserver coefficient of variation of repeated measures of flow-mediated dilation (FMD) using the software (6.7%) was significantly lower than that for traditional manual measurements using the intima-lumen interfaces (24.8%, P < 0.05) and intima-media interfaces (32.5%, P < 0.05). In study 3, 24 healthy volunteers underwent repeat testing twice within 1 wk; the coefficients of variation for between-visit reproducibility of FMD and response to glyceryl trinitrate using the software were 14.7 and 17.6%, respectively. Assuming 80% power and an alpha of 0.05, eight subjects with matched controls would be required, in a parallel designed study, to detect an absolute 2.5% change in FMD. In summary, we have developed a semiautomated computerized vascular ultrasound analysis system that will improve the power of clinical intervention studies to detect small changes in arterial diameter.     

Short-term passive smoking causes endothelial dysfunction via oxidative stress in nonsmokers

Recent studies have shown that passive smoking impairs vascular endothelial function and induces oxidative stress in humans. However, in most of the previous human data regarding tobacco-induced pathophysiology, vascular endothelial dysfunction and oxidative stress have been separately assessed. This study was designed to determine the association between the acute effect of passive smoking on vascular endothelial function and in-vivo oxidative stress status. We studied 30 healthy male Japanese volunteers (32 +/- 7 years) including 15 habitual smokers and 15 nonsmokers. After baseline echocardiographic, hemodynamic recording, and blood sampling, subjects were exposed to passive smoking for 30 min. Endothelium-dependent vasodilation was measured by using % flow-mediated vasodilation (%FMD) of the brachial artery and plasma levels of 8-isoprostane was measured by enzyme immunoassay before and after the passive smoking exposure. Baseline %FMD was lower (4.3% +/- 1.2% vs. 10.9% +/- 3.1%, p < 0.001) and baseline plasma 8-isoprostane level was higher (41.5 +/- 5.8 pg/mL vs. 26.9 +/- 5.4 pg/mL, p < 0.001) in smokers than those in nonsmokers. The %FMD and 8-isoprostane level did not change after passive smoking in smokers. In nonsmokers, however, the %FMD decreased (to 5.0% +/- 1.9%, p < 0.001) and the 8-isoprostane level increased (to 37.8 +/- 9.6 pg/mL, p < 0.001) significantly after 30 min passive smoking exposure, equivalently to the levels of smokers. Sixty corrected samples before and after passive smoking exposure in all patients showed a significant negative correlation between the % FMD and the plasma 8-isoprostane levels (n = 60, r = -0.69, p < 0.001). Even 30 min of passive smoking rapidly impairs vascular endothelial function, which is associated with oxidative stress. Our data provide the pathophysiological insight for the recent epidemiological evidence about the increased risk of coronary heart disease among nonsmokers exposed to passive smoking.     

Loss of the preconditioning effect of rosuvastatin during sustained therapy: a human in vivo study

Studies have demonstrated that the acute administration of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors has protective effects in the setting of ischemia-reperfusion (IR). Previously, we demonstrated that a single dose of rosuvastatin prevented IR-induced endothelial dysfunction in humans through a cyclooxygenase-2-dependent mechanism. Whether the chronic administration of HMG-CoA reductase inhibitors provides similar protection remains controversial and is unknown in humans. Eighteen male volunteers were randomized to receive a single dose of rosuvastatin (20 mg) or placebo. Twenty-four hours later, endothelium-dependent, radial artery flow-mediated dilation (FMD) was measured before and after IR (15 min of upper arm ischemia followed by 15 min of reperfusion). In a separate protocol, 30 healthy volunteers were randomized in a double-blind fashion to receive oral rosuvastatin (20 mg/day) and placebo, rosuvastatin, and celecoxib (100 mg bid) or placebo alone, all for 21 days. Twenty-four hours after the final administration of study medication, FMD was measured before and after IR. Pre-IR FMD was similar between groups in both protocols. In the acute administration protocol, rosuvastatin significantly prevented the blunting of FMD associated with IR (FMD pre-IR: 8.4 ± 1.3%; post-IR: 6.2 ± 1.3%; P = 0.01 ANOVA, treatment group interaction). In the daily administration protocol, IR significantly blunted FMD in the placebo group (FMD pre-IR: 7.5 ± 0.9%; post-IR: 3.3 ± 0.7%; P < 0.001). Chronic treatment with rosuvastatin did not modify this ischemic injury (FMD pre-IR: 6.9 ± 0.4%; post-IR: 1.6 ± 1.0%; P < 0.001; P = NS ANOVA, treatment group interaction). Similarly, FMD responses post-IR in volunteers receiving rosuvastatin and celecoxib did not significantly differ from placebo (FMD pre-IR: 8.3 ± 0.9%; post-IR: 2.1 ± 0.8%; P < 0.001; P = NS ANOVA, treatment group interaction). In contrast to acute administration, chronic rosuvastatin does not prevent the development of IR-induced endothelial dysfunction in normal humans.     

Sympathetic nervous system contributes to the age-related impairment of flow-mediated dilation of the superficial femoral artery

The physiological aging process is associated with endothelial dysfunction, as assessed by flow-mediated dilation (FMD). Aging is also characterized by increased sympathetic tone. Therefore, the aim of the present study is to assess whether acute changes in sympathetic activity alter FMD in the leg. For this purpose, the FMD of the superficial femoral artery was determined in 10 healthy young (22 +/- 1 yr) and 8 healthy older (69 +/- 1 yr) men in three different conditions: 1) at baseline, 2) during reduction of sympathetic activity, and 3) during sympathetic stimulation. Reduction of sympathetic activity was achieved by performing a maximal cycling exercise, leading to postexercise attenuation of the sympathetic responsiveness in the exercised limb. A cold pressor test was used to increase sympathetic activity. Nitroglycerin (NTG) was used to assess endothelium-independent vasodilation in all three conditions. Our results showed that, in older men, the FMD and NTG responses were significantly lower compared with young men (P = 0.001 and P = 0.02, respectively). In older men, sympathetic activity significantly affected the FMD response [repeated-measures (RM) ANOVA: P = 0.01], with a negative correlation between the level of sympathetic activity and FMD (R = -0.41, P = 0.049). This was not the case for NTG responses (ANOVA; P = 0.48). FMD and NTG responses in young men did not differ among the three conditions (RM-ANOVA: P = 0.32 and P = 0.31, respectively). In conclusion, in older men, FMD of the femoral artery is impaired. Local attenuation of the sympathetic responsiveness partly restores the FMD in these subjects. In contrast, in young subjects, acute modulation of the sympathetic nervous system activity does not alter flow-mediated vasodilation in the leg.     

The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

ABSTRACT: BACKGROUND: Previous studies have demonstrated that postprandial hyperglycemia attenuates brachial artery flow-mediated dilation (FMD) in prediabetic patients, in diabetic patients, and even in normal subjects. We have previously reported that postprandial hyperinsulinemia also attenuates FMD. In the present study we evaluated the relationship between different degrees of postprandial attenuation of FMD induced by postprandial hyperglycemia and hyperinsulinemia and differences in ingested carbohydrate content in non-diabetic individuals. METHODS: Thirty-seven healthy subjects with no family history of diabetes were divided into 3 groups: a 75-g oral glucose loading group (OG group) (n = 14), a test meal group (TM group) (n = 12; 400 kcal, carbohydrate content 40.7 g), and a control group (n = 11). The FMD was measured at preload (FMD0) and at 60 minutes (FMD60) and 120 (FMD120) minutes after loading. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were determined at preload (PG0, IRI0) and at 30 (PG30, IRI30), 60 (PG60, IRI60), and 120 (PG120, IRI120) minutes after loading.ResultPercentage decreases from FMD0 to FMD60 were significantly greater in the TM group ([MINUS SIGN]21.19 % [PLUS-MINUS SIGN] 17.90 %; P < 0.001) and the OG group ([MINUS SIGN]17.59 % [PLUS-MINUS SIGN] 26.64 %) than in the control group (6.46 % [PLUS-MINUS SIGN] 9.17 %; P < 0.01), whereas no significant difference was observed between the TM and OG groups. In contrast, the percentage decrease from FMD0 to FMD120 was significantly greater in the OG group ([MINUS SIGN]18.91 % [PLUS-MINUS SIGN] 16.58 %) than in the control group (6.78 % [PLUS-MINUS SIGN] 11.43 %; P < 0.001) or the TM group (5.22 % [PLUS-MINUS SIGN] 37.22 %; P < 0.05), but no significant difference was observed between the control and TM groups. The FMD60 was significantly correlated with HOMA-IR (r = [MINUS SIGN]0.389; P < 0.05). In contrast, FMD120 was significantly correlated with IRI60 (r = [MINUS SIGN]0.462; P < 0.05) and the AUC of IRI (r = [MINUS SIGN]0.468; P < 0.05). Furthermore, the percentage change from FMD0 to FMD120 was significantly correlated with the CV of PG (r = 0.404; P < 0.05), IRI60 (r = 0.401; p < 0.05) and the AUC of IRI (r = 0.427; P < 0.05). No significant correlation was observed between any other FMDs and glucose metabolic variables. CONCLUSION: Differences in the attenuation of postprandial FMD induced by different postprandial insulin levels may occur a long time postprandially but not shortly after a meal.     

Diurnal Variation in Vascular Function: Role of Sleep

Although vascular function is lower in the morning than afternoon, previous studies have not assessed the influence of prior sleep on this diurnal variation. The authors employed a semiconstant routine protocol to study the contribution of prior nocturnal sleep to the previously observed impairment in vascular function in the morning. Brachial artery vascular function was assessed using the flow-mediated dilation technique (FMD) in 9 healthy, physically active males (mean?±?SD: 27?±?9 yrs of age), at 08:00 and 16:00?h following, respectively, 3.29?±?.37 and 3.24?±?.57?h prior sleep estimated using actimetry. Heart rate and systolic and diastolic blood pressures were also measured. The data of the experimental sleep condition were compared with the data of the “normal” diurnal sleep condition, in which FMD measurements were obtained from 21 healthy individuals who slept only during the night, as usual, before the morning test session. The morning-afternoon difference in FMD was 1?±?4% in the experimental sleep condition compared with 3?±?4% in the normal sleep condition (p?=?.04). This difference was explained by FMD being 3?±?3% lower in afternoon following the prior experimental sleep (p?=?.01). These data suggest that FMD is more dependent on the influence of supine sleep than the endogenous circadian timekeeper, in agreement with our previous finding that diurnal variation in FMD is influenced by exercise. These findings also raise the possibility of a lower homeostatic “set point” for vascular function following a period of sleep and in the absence of perturbing hemodynamic fluctuation. (Author correspondence: h.jones1@ljmu.ac.uk)     

瑞舒伐他汀对高胆固醇血症患者的降脂疗效及对血管内皮舒张功能 的影响

目的:探讨瑞舒伐他汀对高胆固醇血症患者的降脂疗效及对血管内皮舒张功能(FMD)的影响。方法:选择我院92例高胆固醇血症患者作为实验组并给予瑞舒伐他汀治疗,另选择同期来我院参加健康体检的健康志愿者42例作为对照组,检测治疗前(T0),以及治疗1个月(T1)、2个月后(T2)的血脂水平及肱动脉FMD和非依赖性血管内皮舒张功能(NMD),并对其治疗的不良反应情况进行统计分析。结果:治疗前,实验组患者血浆中TC、TG和LDL-C水平明显高于对照组,而HDL-C水平显著低于对照组,且差异均具有统计学意义(P0.05)。相对于T0,实验组患者T1和T2血浆中TC、TG和LDL-C水平明显下降,而HDL-C水平显著升高,且差异均具有统计学意义(P0.05)。患者T2时血浆中TC和LDL-C水平明显低于T1的水平(P0.05),而TG和HDL-C水平与T1之间的差异无统计学意义(P0.05);治疗前,实验组患者的FMD值明显低于对照组的健康志愿者(P0.05)。经过瑞舒伐他汀干预2个月后,实验组患者T2时FMD值明显高于T0(P0.05),而T2的NMD与T0之间的差异无统计学意义(P0.05);治疗期间并未出现严重的不良反应。结论:瑞舒伐他汀对老年高胆固醇血症患者降脂效果显著,且有改善FMD的作用。     

Interactions between cocoa flavanols and inorganic nitrate: Additive effects on endothelial function at achievable dietary amounts

Dietary intervention studies have shown that flavanols and inorganic nitrate can improve vascular function, suggesting that these two bioactives may be responsible for beneficial health effects of diets rich in fruits and vegetables. We aimed to study interactions between cocoa flavanols (CF) and nitrate, focusing on absorption, bioavailability, excretion, and efficacy to increase endothelial function. In a double-blind randomized, dose–response crossover study, flow-mediated dilation (FMD) was measured in 15 healthy subjects before and at 1, 2, 3, and 4 h after consumption of CF (1.4–10.9 mg/kg bw) or nitrate (0.1–10 mg/kg bw). To study flavanol–nitrate interactions, an additional intervention trial was performed with nitrate and CF taken in sequence at low and high amounts. FMD was measured before (0 h) and at 1 h after ingestion of nitrate (3 or 8.5 mg/kg bw) or water. Then subjects received a CF drink (2.7 or 10.9 mg/kg bw) or a micro- and macronutrient-matched CF-free drink. FMD was measured at 1, 2, and 4 h thereafter. Blood and urine samples were collected and assessed for CF and nitric oxide (NO) metabolites with HPLC and gas-phase reductive chemiluminescence. Finally, intragastric formation of NO after CF and nitrate consumption was investigated. Both CF and nitrate induced similar intake-dependent increases in FMD. Maximal values were achieved at 1 h postingestion and gradually decreased to reach baseline values at 4 h. These effects were additive at low intake levels, whereas CF did not further increase FMD after high nitrate intake. Nitrate did not affect flavanol absorption, bioavailability, or excretion, but CF enhanced nitrate-related gastric NO formation and attenuated the increase in plasma nitrite after nitrate intake. Both flavanols and inorganic nitrate can improve endothelial function in healthy subjects at intake amounts that are achievable with a normal diet. Even low dietary intake of these bioactives may exert relevant effects on endothelial function when ingested together.     

Combined aerobic and resistance training and vascular function: effect of aerobic exercise before and after resistance training.

Aerobic exercise training combined with resistance training (RT) might prevent the deterioration of vascular function. However, how aerobic exercise performed before or after a bout of RT affects vascular function is unknown. The present study investigates the effect of aerobic exercise before and after RT on vascular function. Thirty-three young, healthy subjects were randomly assigned to groups that ran before RT (BRT: 4 male, 7 female), ran after RT (ART: 4 male, 7 female), or remained sedentary (SED: 3 male, 8 female). The BRT and ART groups performed RT at 80% of one repetition maximum and ran at 60% of the targeted heart rate twice each week for 8 wk. Both brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) after combined training in the BRT group did not change from baseline. In contrast, baPWV after combined training in the ART group reduced from baseline (from 1,025 +/- 43 to 910 +/- 33 cm/s, P < 0.01). Moreover, brachial artery FMD after combined training in the ART group increased from baseline (from 7.3 +/- 0.8 to 9.6 +/- 0.8%, P < 0.01). Brachial artery diameter, mean blood velocity, and blood flow in the BRT and ART groups after combined training increased from baseline (P < 0.05, P < 0.01, and P < 0.001, respectively). These values returned to the baseline during the detraining period. These values did not change in the SED group. These results suggest that although vascular function is not improved by aerobic exercise before RT, performing aerobic exercise thereafter can prevent the deteriorating of vascular function.     

Vascular Dysfunction in Obstructive Sleep Apnea and Type 2 Diabetes Mellitus

Despite the high prevalence of obstructive sleep apnea (OSA) in type 2 diabetes mellitus (DM), the attributable vascular risk from each condition is unknown. We hypothesize that OSA may have a similar effect on vascular function as type 2 diabetes does. Healthy normal‐weight subjects, healthy obese subjects, subjects with type 2 diabetes, and obese subjects with OSA were enrolled. Vascular function was assessed with brachial artery ultrasound for flow‐mediated dilatation (FMD) and in skin microcirculation by laser Doppler flowmetry. One hundred fifty‐three subjects were studied: healthy normal‐weight controls (NCs) (n = 14), healthy obese controls (OCs) (n = 33), subjects with DM (n = 68), and obese subjects with OSA (n = 38). The DM group did not undergo sleep study and thus may have had subclinical OSA. The OSA and type 2 diabetes groups had impaired FMD as compared to both the normal‐weight and OC groups (5.8 ± 3.8%, 5.4 ± 1.6% vs. 9.1 ± 2.5%, 8.3 ± 5.1%, respectively, P < 0.001, post hoc Fischer test). When referenced to the NC group, a multiple linear regression model adjusting for covariates found that baseline brachial artery diameter (β = ?3.75, P < 0.001), OSA (β = ?2.45, P = 0.02) and type 2 diabetes status (β = ?2.31, P = 0.02), negatively predicted % FMD. OSA status did not seem to affect nitroglycerin‐induced vasodilation (endothelium‐independent) of the brachial artery or vascular function in the skin microcirculation. OSA impairs endothelial function in the brachial artery to a similar degree as type 2 diabetes does. OSA, however, does not appear to affect brachial endothelium‐independent vasodilation or skin microcirculatory function. Treatment of OSA in patients with concomitant type 2 diabetes, therefore, may be a potential therapeutic option to improve macro‐, but not microvascular outcomes.     

Tetrahydrobiopterin increases insulin sensitivity in patients with type 2 diabetes and coronary heart disease

Tetrahydrobiopterin (BH(4)) is an essential cofactor of nitric oxide synthase that improves endothelial function in diabetics, smokers, and patients with hypercholesterolemia. Insulin resistance has been suggested as a contributing factor in the development of endothelial dysfunction via an abnormal pteridine metabolism. We hypothesized that BH(4) would restore flow-mediated vasodilation (FMD, endothelial-dependent vasodilation), which may affect insulin resistance in type 2 diabetic patients. Thirty-two subjects (12 type 2 diabetic subjects, 10 matched nondiabetic subjects, and 10 healthy unmatched subjects) underwent infusion of BH(4) or saline in a random crossover study. Insulin sensitivity index (S(I)) was measured by hyperinsulinemic isoglycemic clamp. FMD was measured using ultrasonography. BH(4) significantly increased S(I) in the type 2 diabetics [3.6 +/- 0.6 vs. 4.9 +/- 0.7 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P < 0.05], while having no effects in nondiabetics [8.9 +/- 1.1 vs. 9.0 +/- 0.9 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.92] or in healthy subjects [17.5 +/- 1.6 vs. 18 +/- 1.8 x 10(-4) dl.kg(-1).min(-1)/(microU/ml), P = 0.87]. BH(4) did not affect the relative changes in brachial artery diameter from baseline FMD (%) in type 2 diabetic subjects (2.3 +/- 0.8 vs. 1.8 +/- 1.0%, P = 0.42), nondiabetic subjects (5.3 +/- 1.1 vs. 6.6 +/- 0.9%, P = 0.32), or healthy subjects (11.9 +/- 0.6 vs. 11.0 +/- 1.0%, P = 0.48). In conclusion, BH(4) significantly increases insulin sensitivity in type 2 diabetic patients without any discernible improvement in endothelial function.     

Effect of acute sympathetic nervous system activation on flow-mediated dilation of brachial artery

We tested the hypothesis that flow-mediated dilation (FMD) of the brachial artery would be impaired by acute increases in sympathetic nervous system activity (SNA) in models where similar peak shear stress stimulus was achieved by varying the duration of forearm muscle ischemia. Eleven healthy young men were studied under four different conditions, each with its own control: lower body suction (LBS), cold pressor test (CPT), mental arithmetic task (MAT), and activation of muscle chemoreflex (MCR). The duration of ischemia before observation of FMD by ultrasound imaging was 5 min each for control, LBS, and CPT; 3 min for MAT; and 2-min for MCR. Peak shear rate was not different between control and any of the SNA conditions, although total shear in the first minute was reduced in MAT. MCR was the only condition in which brachial artery vasoconstriction was observed before forearm occlusion [4.38 (SD 0.53) vs. control 4.60 (SD 0.53) mm, P < 0.05]; however, diameter increased to the same absolute value as that of the control, so the percent FMD was greater for MCR [9.85 (SD 2.33) vs. control 5.29 (SD 1.50)%]. Blunting of the FMD response occurred only in the CPT model [1.51 (SD 1.20)%]. During SNA, the increase in plasma cortisol from baseline was significant only for MCR; the increase in plasma norepinephrine was significant for MCR, LBS, and CPT; and the increase in epinephrine was significant only for MCR. These results showed that the four models employed to achieve increases in SNA had different effects on baseline brachial artery diameter and that blunted FMD is not a general response to increased SNA.     

The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress

An inverse relationship between baseline artery diameter (BAD) and flow-mediated vasodilation (FMD) has been identified using reactive hyperemia (RH) to create a shear stress (SS) stimulus in human conduit arteries. However, RH creates a SS stimulus that is inversely related to BAD. The purpose of this study was to compare FMD in response to matched levels of SS in two differently sized upper limb arteries [brachial (BA) and radial (RA) artery]. With the use of exercise, three distinct, shear rate (SR) stimuli were created (SR = blood velocity/vessel diameter; estimate of SS) in the RA and BA. Artery diameter and mean blood velocity were assessed with echo and Doppler ultrasound in 15 healthy male subjects (19-25 yr). Data are means ± SE. Subjects performed 6 min of adductor pollicis and handgrip exercise to increase SR in the RA and BA, respectively. Exercise intensity was modulated to achieve uniformity in SR between arteries. The three distinct SR levels were as follows: steady-state exercise 39.8 ± 0.6, 57.3 ± 0.7, and 72.4 ± 1.2 s(-1) (P < 0.001). %FMD and AbsFMD (mm) at the end of exercise were greater in the RA vs. the BA at each shear level [at the highest level: RA = 15.7 ± 1.5%, BA = 5.4 ± 0.8% (P < 0.001)]. The mean slope of the within-subject SR-%FMD regression line was greater in the RA (RA = 0.33 ± 0.04, BA = 0.13 ± 0.02, P < 0.001), and a strong within-subjects relationship between %FMD and SR was observed in both arteries (RA: r(2) = 0.92 ± 0.02; BA: r(2) = 0.90 ± 0.03). Within the RA, there was a significant relationship between baseline diameter and %FMD; however, this relationship was not present in the BA (RA: r(2) = 0.76, P < 0.001; BA: r(2) = 0.03, P = 0.541). These findings suggest that the response to SS is not uniform across differently sized vessels, which is in agreement with previous studies.     

Plasma nitrite reserve and endothelial function in the human forearm circulation

Attenuation of endothelium-derived nitric oxide (NO) synthesis is a hallmark of endothelial dysfunction. Early detection of this disorder may have therapeutic and prognostic implications. Plasma nitrite mirrors acute and chronic changes in endothelial NO-synthase activity. We hypothesized that local plasma nitrite concentration increases during reactive hyperemia of the forearm, reflecting endothelial function. In healthy subjects (n = 11) plasma nitrite and nitrate were determined at baseline and during reactive hyperemia of the forearm using reductive gas-phase chemiluminescence and flow-injection analysis, respectively. Endothelium-dependent dilation of the brachial artery was measured as flow-mediated dilation (FMD) using high-resolution ultrasound. Results were compared to patients with endothelial dysfunction as defined by reduced FMD (n = 11). Reactive hyperemia of the forearm increased local plasma nitrite concentration from 68 +/- 5 to 126 +/- 13 nmol/L (p < 0.01), whereas in endothelial dysfunction nitrite remained unaffected (116 +/- 12 to 104 +/- 10 nmol/L; n.s.), corresponding to nitrite reserves of 94 +/- 21 and -8 +/- 4%. This was accompanied by a significantly greater increase in brachial artery diameter (FMD: 8.5 +/- 0.4% vs 2.9 +/- 0.5%, for healthy subjects and endothelial dysfunction, respectively; p < 0.001). This observation suggests that nitrite changes reflect endothelial function. Assessment of local plasma nitrite during reactive hyperemia may open new avenues in the diagnosis of vascular function.