Ryan A. Harris

The effect of acute exercise on endothelial function following a high-fat meal.

The transient impairment of endothelial function following a high-fat meal is well established. Brachial artery flow-mediated dilation (FMD) decreases between 2 and 6xa0h post ingestion. Whether this impairment can be reduced with acute aerobic exercise has not been investigated. The purpose of this study was to investigate if a single sustained aerobic exercise session can counteract the postprandial attenuation in brachial artery FMD associated with the ingestion of a high-fat meal. Eight apparently healthy adults (five men, three women), age 25.5xa0±xa00.8xa0years, performed three treatment conditions in a counter-balanced design: (1) low-fat meal alone (LFM), (2) high-fat meal alone (HFM), and (3) one session of aerobic exercise presented 2xa0h after ingesting a high-fat meal (HFM-EX). The examination of brachial artery FMD was performed at baseline and 4xa0h following the ingestion of the meal for each treatment condition. A 3xa0×xa02 (treatmentxa0×xa0time) repeated measures ANOVA exhibited a significant interaction (Pxa0=xa00.019). Preprandial FMDs were similar (Pxa0=xa00.863) among all three treatment conditions. The FMDs following the LFM (7.18xa0±xa01.31%) and HFM-EX (8.72xa0±xa00.94%) were significantly higher (Pxa0=xa00.001) than the FMD following the HFM (4.29xa0±xa01.64%). FMD was significantly elevated above preprandial values following the HFM-EX (5.61xa0±xa01.54 to 8.72xa0±xa00.94%, Pxa0=xa00.005) but was unchanged following the LFM (6.17xa0±xa00.94 to 7.18xa0±xa01.31%, Pxa0=xa00.317) and the HFM (5.73xa0±xa01.23 to 4.29xa0±xa01.64%, Pxa0=xa00.160). These findings suggest that a single aerobic exercise session cannot only counteract the postprandial endothelial dysfunction induced by the ingestion of a high-fat meal, but also increase brachial artery FMD in apparently healthy adults.

The Flow-mediated Dilation Response to Acute Exercise in Overweight Active and Inactive Men

Objective: Inflammation has been found to play a role in the etiology of cardiovascular disease as well as provoke endothelial dysfunction. Inflammatory cytokines associated with endothelial function are interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α). IL‐6 is exercise intensity dependent and has been shown to inhibit TNF‐α expression directly. The aim of this study was to investigate the interaction of IL‐6 and TNF‐α on endothelial function in response to acute exercise in overweight men exhibiting different physical activity profiles.

Variability of flow-mediated dilation measurements with repetitive reactive hyperemia

To capture the response of an acute intervention, multiple post intervention measurements of flow-mediated dilation (FMD) must be performed. The effect of repetitive reactive hyperemia on endothelial function and the measurement of FMD are unknown. The purpose of this investigation was (1) to examine the effect of repetitive reactive hyperemia on brachial artery FMD and (2) to determine whether brachial artery FMD is stable during a 2-h morning period. We investigated FMD in 20 apparently healthy college students on three randomized treatment days every 30 min (T30), 60 min (T60), and 120 min (T120) throughout a 2-h morning period (08.00 h to 10.00 h). An ANOVA (p > 0.05) and ICC (>0.40) were both needed to confirm no difference among repetitive reactive hyperemia treatments. In response to repetitive reactive hyperemia, there was no difference (p = 0.307; ICC > 0.40) within the first and last FMD measurements of each treatment condition or between treatment conditions (p = 0.344; ICC > 0.40). FMD was similar (p = 0.348) throughout the 2-h morning period. In conclusion, repetitive reactive hyperemia over a 2-h period has no effect on FMD measurements in apparently healthy college students. In addition, this study found no time trends for FMD measurements during the 2-h morning period to allow for pre/post intervention FMD measurements.

Can the measurement of brachial artery flow-mediated dilation be applied to the acute exercise model?

The measurement of flow-mediated dilation using high-resolution ultrasound has been utilized extensively in interventional trials evaluating the salutary effect of drugs and lifestyle modifications (i.e. diet or exercise training) on endothelial function; however, until recently researchers have not used flow-mediated dilation to examine the role of a single bout of exercise on vascular function. Utilizing the acute exercise model can be advantageous as it allows for an efficient manipulation of exercise variables (i.e. mode, intensity, duration, etc.) and permits greater experimental control of confounding variables. Given that the application of flow-mediated dilation in the acute exercise paradigm is expanding, the purpose of this review is to discuss methodological and physiological factors pertinent to flow-mediated dilation in the context of acute exercise. Although the scientific rationale for evaluating endothelial function in response to acute exercise is sound, few concerns warrant attention when interpreting flow-mediated dilation data following acute exercise. The following questions will be addressed in the present review: Does the measurement of flow-mediated dilation influence subsequent serial measures of flow-mediated dilation? Do we need to account for diurnal variation? Is there an optimal time to measure post-exercise flow-mediated dilation? Is the post-exercise flow-mediated dilation reproducible? How is flow-mediated dilation interpreted considering the hemodynamic and sympathetic changes associated with acute exercise? Can the measurement of endothelial-independent dilation affect the exercise? Evidence exists to support the methodological appropriateness for employing flow-mediated dilation in the acute exercise model; however, further research is warranted to clarify its interpretation following acute exercise.

A comparison between active- and reactive-hyperaemia-induced brachial artery vasodilation

The measurement of brachial artery vasodilation in response to a hyperaemic stimulus has been used extensively to assess changes in endothelial function. However, whether or not similar changes occur in response to an active hyperaemic stimulus is unknown. The purpose of the present study was to compare brachial artery vasodilation in response to an active compared with a reactive hyperaemic stimulus following a known perturbation of endothelial function. Eight apparently healthy adults were assigned to four treatment conditions in a counter-balanced design: (i) low-fat meal with active hyperaemic stimulus (LFM-A), (ii) high-fat meal with active hyperaemic stimulus (HFM-A), (iii) low-fat meal with reactive hyperaemic stimulus (LFM-R), and (iv) high-fat meal with reactive hyperaemic stimulus (HFM-R). Meals were ingested at 08:00 hours on each treatment day. Brachial artery vasodilation was assessed via ultrasound 4 h after ingestion of each meal. The active hyperaemic stimulus was induced by 5 min of rhythmic handgrip exercise, whereas reactive hyperaemia was induced by 5 min of forearm occlusion. Brachial artery vasodilation was expressed as the percentage change in diameter from baseline to post-active/reactive hyperaemia. Using a 2x2 repeated measures ANOVA, a significant stimulusxmeal interaction (P=0.025) was found. Simple main effects revealed no difference (P=0.541) in brachial artery vasodilation between LFM-A (5.75+/-1.64%) and HFM-A (6.39+/-1.45%); however, a significant decrease (P=0.014) in brachial artery vasodilation was found in the HFM-R (4.29+/-1.64%) compared with the LFM-R (7.18+/-1.13%) treatment. In conclusion, the measurement of brachial artery vasodilation in response to active hyperaemia did not detect a change in endothelial function following a single perturbation meal, whereas reactive hyperaemia did.

Characterization of the brachial artery shear stress following walking exercise

Abstract Habitual exercise provides repeated episodes of elevated vascular shear stress (SS), which may be a mechanism for repair of endothelial dysfunction in disease. Our aim was to determine the brachial artery SS during the 3–hour period following single bouts of low, moderate, and high-intensity walking exercise. In a randomized crossover design, 14 men walked for 45 minutes on a treadmill at 25%, 50% and 75% of VO2peak separated by 2–7 days. Using Doppler ultrasonography, brachial artery SS was assessed immediately after exercise and then hourly for 3 hours. High-intensity walking elicited greater (pu2004<u20040.05) post-exercise SS compared with low and moderate intensity. In addition, a 3u2004xu20044 (intensityu2004xu2004time) ANOVA indicated an absence of interaction (pu2004=u20040.369) and a decline in post-exercise SS over time (pu2004<u20040.0001) which was abolished after 2 hours. Thus, we found that brachial artery SS is greatest following high-intensity walking and that the rate of decline in SS is similar across all walking intensities.

Angiotensin II in the Elderly: Impact of Angiotensin II Type 1 Receptor Sensitivity on Peripheral Hemodynamics

Exercise hyperemia is attenuated in the elderly, which may be attributed to local vasoregulatory pathways within the skeletal muscle vasculature. Therefore, we sought to determine whether healthy aging is associated with changes in angiotensin II (Ang II) receptor sensitivity through measurements of leg blood flow in resting and exercising skeletal muscle. In 12 (n=6 young, 24±1 years; n=6 older, 68±3 years) healthy volunteers, we determined changes in leg blood flow (ultrasound Doppler) before and during intra-arterial infusion of Ang II (0.8 ng/mL of leg blood flow per minute). Heart rate, arterial blood pressure, common femoral artery diameter, and mean blood velocity were measured at rest and during knee-extensor exercise at 20% and 40% of the maximal work rate (WRmax). At rest, Ang II infusion decreased leg blood flow to a greater extent in older (−61±8%) subjects compared with younger subjects (−31±5%). Compared with rest, Ang II–mediated vasoconstriction (leg blood flow) during exercise was diminished in both older and younger subjects at 20% (older: −7±5%; younger: −21±2%) and 40% WRmax (older: −5±4%; younger: −9±3%). These data identify a clear age-related hypersensitivity to Ang II in the resting leg, which may contribute to the recognized decrement in leg blood flow in this cohort. However, the diminished vasoconstriction to Ang II during exercise suggests that the elevation in Ang II type 1 receptor sensitivity documented at rest does not contribute significantly to the blunted exercise hyperemia experienced with advancing age.

Vascular consequences of a high-fat meal in physically active and inactive adults

Habitually active adults (ACT) typically exhibit lower postprandial lipemia, a condition that may attenuate oxidative stress and endothelial dysfunction following a high-fat meal (HFM), compared with inactive adults (INA). Our objective was to compare triglycerides (TAG), superoxide dismutase activity (SOD), oxidative stress (thiobarbituric reactive substances; TBARS), and brachial artery flow-mediated dilation (FMD%) before and after an HFM challenge in ACT and INA. ACT (n = 7) and INA (n = 7) subjects were matched for body mass index, age, and sex. Plasma TAG, SOD, TBARS, and FMD% were measured at baseline and 4 h after an HFM challenge. TAG significantly increased following the HFM in INA (4.15xa0± 3.79xa0mmol·L–1 vs. 8.07xa0± 5.12 mmol·L–1) and in ACT (2.16xa0± 0.55xa0mmol·L–1 vs. 3.24xa0± 1.40xa0mmol·L–1). Baseline TBARS were greater in ACT and remained unchanged in response to the HFM in both INA (5.1xa0± 2.7xa0mmol·L–1 vs. 6.9xa0± 2.9xa0mmol·L–1) and ACT (8.6xa0± 2.0xa0mmol·L–1 vs. 7.9xa0± 1.9xa0mmol·L–1). ACT exhibited greater...

Premenopausal women exhibit an inherent protection of endothelial function following a high-fat meal

Endogenous estrogens likely increase blood flow and subsequently shear stress but have also been associated with improved endothelial function and cardiovascular protection. In contrast, a high-fat meal is thought to reduce endothelial function and increase cardiovascular risk. Therefore, we tested the hypotheses that fluctuating hormones across the menstrual cycle (1) facilitate an increase in shear rate and explain phase-specific differences in flow-mediated dilation (FMD) and (2) provide vascular protection against the insult of a high-fat meal. Flow-mediated dilation was determined at baseline and 4 hours following a high-fat meal in young women during the menses (M), follicular (F), and luteal (L) phases of the menstrual cycle. Male control participants were studied once. 17β-Estradiol was elevated (P < .05) during the F (5.3 ± 0.7 pg/mL) and L (5.2 ± 0.6 pg/mL) phases when compared to the M (3.9 ± 0.5 pg/mL) phase, and this was accompanied by an elevated FMD in the F and L phases (12.4 ± 1.4% and 11.2 ± 0.9%, respectively) compared to M (8.0 ± 0.9) with no change in shear rate. Female postprandial FMD was similar throughout the menstrual cycle, while men exhibited a 50% reduction (6.4 ± 1 to 3.3 ± 1%; P < .05). Interestingly, the postprandial FMD response was not associated with concentrations of either 17β-estradiol or progesterone. Despite acutely changing ovarian hormones across the menstrual cycle, shear stress is invariant and therefore does not account for the changes in FMD. Additionally, young women appear to have an inherent vascular protection from the insult of a high-fat meal, perhaps helping to explain sex-specific differences in cardiovascular risk.

The role of redox balance

Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary function, inflammation, free radical production, vascular dysfunction, and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double-blind, randomized, placebo-controlled, crossover design, patients with COPD and controls were ingested placebo or the antioxidant cocktail (vitamin C, vitamin E, &agr;-lipoic acid) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (vitamin C and superoxide dismutase activity) and higher levels of oxidative stress (thiobarbituic acid reactive species) in comparison with controls. The patients also displayed lower basal flow-mediated dilation (P<0.05), which was significantly improved with antioxidant cocktail (3.1±0.5 versus 4.7±0.6%; P<0.05; placebo versus antioxidant cocktail), but not controls (6.7±0.6 versus 6.9±0.7%; P>0.05; placebo versus antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in patients with COPD (14±1 versus 11±1 m·s−1; P<0.05; placebo versus antioxidant cocktail) while not affecting controls (11±2 versus 10±1 m·s−1; P>0.05; placebo versus antioxidant). Patients with COPD exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically mediated vascular dysfunction may be an important mechanism contributing to this population’s greater risk and incidence of cardiovascular disease.