Skipping breakfast does not accelerate the hyperglycemia-induced endothelial dysfunction but reduces blood flow of the brachial artery in young men.

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

Acute aerobic exercise enhances cerebrovascular shear-mediated dilation in young adults: the role of cerebral shear.

Exercise-induced increases in shear rate (SR) acutely improve peripheral endothelial function, but the presence of this mechanism in cerebral arteries remains unclear. Thus, we evaluated shear-mediated dilation of the internal carotid artery (ICA), which is an index of cerebrovascular endothelial function, before and after exercise. Shear-mediated dilation was measured with 30 s of hypercapnia in 16 young adults before and 10 min after 30 min of sitting rest (CON) or three cycling exercises on four separate days. The target exercise intensity was 80% of oxygen uptake at the ventilatory threshold. To manipulate the ICA SR during exercise, participants breathed spontaneously (ExSB, SR increase) or hyperventilated without (ExHV, no increase in SR) or with ([Formula: see text], restoration of SR increase) addition of CO2 to inspiratory air. Shear-mediated dilation was calculated as a percent increase in diameter from baseline. Doppler ultrasound measures ICA velocity and diameter. The CON trial revealed that 30 min of sitting did not alter shear-mediated dilation (4.34 ± 1.37% to 3.44 ± 1.23%, P = 0.052). ICA dilation after exercise compared with preexercise levels increased in the ExSB trial (3.32 ± 1.37% to 4.74 ± 1.84%, P < 0.01), remained unchanged in the ExHV trial (4.07 ± 1.55% to 3.21 ± 1.48%, P = 0.07), but was elevated in the [Formula: see text] trial (3.35 ± 1.15% to 4.33 ± 2.12%, P = 0.04). Our results indicate that exercise-induced increases in cerebral shear may play a crucial role in improving cerebrovascular endothelial function after acute exercise in young adults.NEW & NOTEWORTHY We found that 30-min cycling (target intensity was 80% of the ventilatory threshold) with increasing shear of the internal carotid artery (ICA) enhanced transient hypercapnia-induced shear-mediated dilation of the ICA, reflecting improved cerebrovascular endothelial function. This enhancement of ICA dilation was diminished by suppressing the exercise-induced increase in ICA shear via hyperventilation. Our results indicate that increases in cerebral shear may be a key stimulus for improving cerebrovascular endothelial function after exercise in young adults.

Handgrip exercise does not alter CO2 -mediated cerebrovascular flow-mediated dilation.

Handgrip exercise (HG), a small muscle exercise, improves cognitive function and is expected to provide a useful exercise mode to maintain cerebral health. However, the effect of HG on cerebral blood flow regulation is not fully understood. The present study aimed to examine the effect of acute HG on cerebral endothelial function as one of the essential cerebral blood flow regulatory functions. Thirteen healthy young participants performed interval HG, consisting of 4 sets of 2 min HG at 25% of maximum voluntary contraction with 3 min recovery between each set. Cognitive performance was evaluated before and at 5 and 60 min after interval HG using the Go/No-Go task (reaction time and accuracy). The diameter and blood velocity of the internal carotid artery (ICA) were measured using a duplex Doppler ultrasound system. To assess cerebral endothelial function, hypercapnia (30 s of hypercapnia stimulation, end-tidal partial pressure of CO2 : +9 mmHg)-induced cerebrovascular flow-mediated dilatation (cFMD) was induced, calculated as relative peak dilatation from baseline diameter. The shear rate (SR) was calculated using the diameter and blood velocity of the ICA. As a result, cognitive performance improved only at 5 min after interval HG (reaction time, P = 0.008; accuracy, P = 0.186), whereas ICA SR during interval HG and cFMD after interval HG were unchanged (P = 0.313 and P = 0.440, respectively). These results suggest that enhancement in cerebral endothelial function is not an essential mechanism responsible for acute HG-induced cognitive improvement. NEW FINDINGS: What is the central question of this study? Does handgrip exercise, a small muscle exercise, improve cerebral endothelial function? What is the main finding and its importance? Acute interval isometric handgrip exercise (2 min of exercise at 25% maximum voluntary contraction, followed by 3 min of recovery, repeated for a total of 4 sets) did not improve cerebral endothelial function. Since the cerebrovascular shear rate did not change during exercise, it is possible that acute handgrip exercise is not sufficient stimulation to improve cerebral endothelial function.

Can Alterations in Cerebrovascular CO2 Reactivity Be Identified Using Transfer Function Analysis without the Requirement for Carbon Dioxide Inhalation?

The present study aimed to examine the validity of a novel method to assess cerebrovascular carbon dioxide (CO2) reactivity (CVR) that does not require a CO2 inhalation challenge, e.g., for use in patients with respiratory disease or the elderly, etc. In twenty-one healthy participants, CVR responses to orthostatic stress (50° head-up tilt, HUT) were assessed using two methods: (1) the traditional CO2 inhalation method, and (2) transfer function analysis (TFA) between middle cerebral artery blood velocity (MCA V) and predicted arterial partial pressure of CO2 (PaCO2) during spontaneous respiration. During HUT, MCA V steady-state (i.e., magnitude) and MCA V onset (i.e., time constant) responses to CO2 inhalation were decreased (p < 0.001) and increased (p = 0.001), respectively, indicative of attenuated CVR. In contrast, TFA gain in the very low-frequency range (VLF, 0.005-0.024 Hz) was unchanged, while the TFA phase in the VLF approached zero during HUT (-0.38 ± 0.59 vs. 0.31 ± 0.78 radians, supine vs. HUT; p = 0.003), indicative of a shorter time (i.e., improved) response of CVR. These findings indicate that CVR metrics determined by TFA without a CO2 inhalation do not track HUT-evoked reductions in CVR identified using CO2 inhalation, suggesting that enhanced cerebral blood flow response to a change in CO2 using CO2 inhalation is necessary to assess CVR adequately.

Dynamic resistance exercise-induced pressor response does not alter hypercapnia-induced cerebral vasodilation in young adults.

Excessive arterial pressure elevation induced by resistance exercise (RE) attenuates peripheral vasodilatory function, but its effect on cerebrovascular function is unknown. We aimed to evaluate the effect of different pressor responses to RE on hypercapnia-induced vasodilation of the internal carotid artery (ICA), an index of cerebrovascular function. To manipulate pressor responses to RE, 15 healthy young adults (11M/4F) performed two RE: high intensity with low repetitions (HL) and low intensity with high repetitions (LH) dynamic knee extension. ICA dilation, induced by 3 min of hypercapnia, was measured before and 10 min after RE using Doppler ultrasound. HL exercise elicited a greater pressor response than LH exercise. In relaxation phases of RE, ICA blood velocity increased in both HL and LH trials. However, ICA shear rate did not significantly increase in either trial (P = 0.06). Consequently, neither exercise altered post-exercise hypercapnia-induced ICA dilation (HL, 3.9 ± 1.9% to 5.1 ± 1.7%; LH, 4.6 ± 1.4% to 4.8 ± 1.8%; P > 0.05 for all). When viewed individually, the changes in ICA shear rate were positively correlated with changes in end-tidal partial pressure of carbon dioxide (PETCO2) (r = 0.46, P < 0.01) than with mean arterial pressure (r = 0.32, P = 0.02). These findings suggest that the effects of RE-induced pressor response on cerebrovascular function may be different from peripheral arteries. An increase in PETCO2 during the relaxation phase may play a more crucial role than elevated pressure in increasing cerebral shear during dynamic RE.

Hypoxia offsets the decline in brachial artery flow-mediated dilation after acute inactivity.

Intermittent (IH), as opposed to continuous hypoxia (CH), is thought to have beneficial effects on cardiovascular function and health. In the present study, we examined the acute effects of IH and CH (∼80% pulse oxygen saturation via 10% oxygen tank) on peripheral vascular function. Brachial artery flow-mediated dilation (FMD) was used to assess vascular function in 12 young adults (23 ± 5 yr; 8 M/4 F) before and after 50 min of IH (5 cycles; 4-min normoxia/6-min hypoxia per cycle), CH (20-min normoxia followed by 30-min hypoxia), or time control (50-min normoxia) interventions. Brachial artery diameter and velocity were measured using Doppler ultrasound to assess blood flow and shear rate. The total change in shear rate was greater during IH (634 ± 1,073·s-1, P < 0.05) and CH (321 ± 833·s-1, P = 0.05) than during time control (-412 ± 789·s-1). %FMD was reduced following time control (7.4 ± 1.2 to 5.9 ± 1.1%, P < 0.05) but was maintained following both hypoxia trials (IH: 7.2 ± 1.5 to 7.5 ± 1.5%, P = 0.52; CH: 6.9 ± 1.6 to 6.8 ± 1.4%, P = 0.73). Normalized %FMD for shear rate area under the curve (%FMDSRAUC) was reduced following the time control trial (4.2 ± 1.4 to 3.7 ± 0.9%, P < 0.05) with no change observed with CH (4.0 ± 1.5 to 3.9 ± 1.4%, P = 0.71). However, %FMDSRAUC increased with IH (3.8 ± 1.1 to 4.5 ± 1.5%, P < 0.05). Our data suggest that acute exposure to hypoxia (both intermittently and continuously) offsets the decline in vascular function after brief inactivity. The potential beneficial effect of hypoxia on peripheral vascular function observed in the current study may be associated with enhanced brachial artery shear in response to the hypoxic challenge.

High-but not moderate-intensity exercise acutely attenuates hypercapnia-induced vasodilation of the internal carotid artery in young men.

PURPOSE: Exercise-induced increases in shear rate (SR) across different exercise intensities may differentially affect hypercapnia-induced vasodilation of the internal carotid artery (ICA), a potential index of cerebrovascular function. We aimed to elucidate the effects of exercise intensity on ICA SR during exercise and post-exercise hypercapnia-induced vasodilation of the ICA in young men. METHODS: Twelve healthy men completed 30 min of cycling at moderate [MIE; 65 ± 5% of age-predicted maximal heart rate (HRmax)] and high (HIE; 85 ± 5% HRmax) intensities. Hypercapnia-induced vasodilation was induced by 3 min of hypercapnia (target end-tidal partial pressure of CO2 + 10 mmHg) and was assessed at pre-exercise, 5 min and 60 min after exercise. Doppler ultrasound was used to measure ICA diameter and blood velocity during exercise and hypercapnia tests. RESULTS: SR was not altered during either exercise (interaction and main effects of time; both P > 0.05). ICA conductance decreased during HIE from resting values (5.1 ± 1.3 to 3.2 ± 1.0 mL·min-1·mmHg-1; P < 0.01) but not during MIE (5.0 ± 1.3 to 4.0 ± 0.8 mL·min-1·mmHg-1; P = 0.11). Consequently, hypercapnia-induced vasodilation declined immediately after HIE (6.9 ± 1.7% to 4.0 ± 1.4%; P < 0.01), but not after MIE (7.2 ± 2.1% to 7.3 ± 1.8%; P > 0.05). Sixty minutes after exercise, hypercapnia-induced vasodilation returned to baseline values in both trials (MIE 8.0 ± 3.1%; HIE 6.4 ± 2.9%; both P > 0.05). CONCLUSION: The present study showed blunted hypercapnia-induced vasodilation of the ICA immediately after high-intensity exercise, but not a moderate-intensity exercise in young men. Given that the acute response is partly linked to the adaptive response in the peripheral endothelial function, the effects of aerobic training on cerebrovascular health may vary depending on exercise intensity.

Greater increase in internal carotid artery shear rate during aerobic interval compared to continuous exercise in healthy adult men.

Interval exercise has been determined to be more effective than continuous exercise for achieving improvement in the cardiovascular function of individuals suffering from cardiovascular disease. However, whether interval exercise improves the cerebrovascular function remains unclear. As per our hypothesis, interval exercise induces a higher cerebrovascular shear rate (SR) than continuous exercise. In this study, 11 adult men randomly performed continuous exercise for 12 min or work-equivalent (57.6 kJ/exercise session) interval exercise of semi-recumbent cycling. The SR in the internal carotid artery (ICA) represents an index of the cerebrovascular SR, which was measured during both the exercises using Doppler ultrasonography. Both the aerobic exercise modes increased the ICA SR. Moreover, the average ICA SR of the interval exercise for the final 4 min of exercise or 2 min of recovery was significantly higher than that for continuous exercise (exercise, 351 ± 75 vs. 330 ± 61/s, p = .038; recovery, 327 ± 86 vs. 290 ± 56/s, p = .014). To our knowledge, this is the first study to show that aerobic interval exercise increased the ICA SR more than equivalent work volume of aerobic continuous exercise. Thus, aerobic interval exercise may be more effective at stimulating the cerebrovasculature, resulting in greater improvements in cerebrovascular function as compared to continuous aerobic exercise in healthy adult men. These findings provide some important information that would help enhance exercise therapy programs for patients with arteriosclerosis, especially in the cerebral circulation.

Effect of Age and Acute Exercise on Circulating Angioregulatory Factors.

The balance of angiogenic factors, including vascular endothelial growth factor (VEGF), and angiostatic factors, like thrombospondin-1 (TSP-1) and endostatin, controls striated muscle angiogenic responses to exercise training. The effect of age on circulating levels of these factors following a bout of exercise is unclear. The authors hypothesized that older adults would have lower circulating VEGF but higher TSP-1 and endostatin after exercise compared with young adults. Ten young and nine older participants cycled for 45 min at 60% estimated HRmax. Serum [VEGF], [TSP-1], and [endostatin] obtained before (PREX), immediately after (POSTX0), and 3 hr after (POSTX3) exercise were analyzed. [VEGF] increased in older adults only from PREX to POSTX0 (p < .05). [TSP-1] increased in both age groups (p < .05). There was no effect of age or exercise on [endostatin]. In conclusion, immediately after exercise, both groups had a similar increase in [TSP-1], but [VEGF] increased in older adults only.

Effects of menstrual cycle and menopause on internal carotid artery shear-mediated dilation in women.

This study aimed to elucidate the effects of change in estrogen during the menstrual cycle and menopause on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation of the ICA and serum estradiol were measured in 11 premenopausal (Pre-M, 21 ± 1 yr), 13 perimenopausal (Peri-M, 49 ± 2 yr), and 10 postmenopausal (Post-M, 65 ± 7 yr) women. Measurements were made twice within the Pre-M group at their early follicular (EF, lower estradiol) and late follicular (LF, higher estradiol) phases. Shear-mediated dilation was induced by 3 min of hypercapnia (target PETCO2 + 10 mmHg from individual baseline) and was calculated as the percent rise in peak diameter relative to baseline diameter. ICA diameter and blood velocity were simultaneously measured by Doppler ultrasound. In Pre-M, shear-mediated dilation was higher during the LF phase than during the EF phase (P < 0.01). Comparing all groups, shear-mediated dilation was reduced across the menopausal transition (P < 0.01), and Pre-M during the LF phase showed the highest value (8.9 ± 1.4%) compared with other groups (Pre-M in EF, 6.4 ± 1.1%; Peri-M, 5.5 ± 1.3%; Post-M, 5.2 ± 1.9%, P < 0.05 for all). Shear-mediated dilation was positively correlated with serum estradiol even after adjustment of age (P < 0.01, r = 0.55, age-adjusted; P = 0.02, r = 0.35). Collectively, these data indicate that controlling the menstrual cycle phase is necessary for the cross-sectional assessments of shear-mediated dilation of the ICA in premenopausal women. Moreover, current findings suggest that a decline in cerebrovascular endothelial function may be partly related to the reduced circulating estrogen levels in peri- and postmenopausal women.NEW & NOTEWORTHY The present study evaluated the effects of the menstrual cycle and menopause stages on the shear-mediated dilation of the ICA, a potential index of cerebrovascular endothelial function, in pre-, peri-, and postmenopausal women. Shear-mediated dilation of the ICA was increased from the low- to high-estradiol phases in naturally cycling premenopausal women and was reduced with advancing menopause stages. Furthermore, lower estradiol was associated with reduced shear-mediated dilation of the ICA, independent of age.

Greater α1-adrenergic-mediated vasoconstriction in contracting skeletal muscle of patients with type 2 diabetes.

Patients with type 2 diabetes mellitus (T2DM) exhibit diminished exercise capacity likely attributable to reduced skeletal muscle blood flow (i.e., exercise hyperemia). A potential underlying mechanism of the impaired hyperemic response to exercise could be inadequate blunting of sympathetic-mediated vasoconstriction (i.e., poor functional sympatholysis). Therefore, we studied the hyperemic and vasodilatory responses to handgrip exercise in patients with T2DM as well as vasoconstriction to selective α-agonist infusion. Forearm blood flow (FBF) and vascular conductance (FVC) were examined in patients with T2DM (n = 30) as well as nondiabetic controls (n = 15) with similar age (59 ± 9 vs. 60 ± 9 yr, P = 0.69) and body mass index (31.4 ± 5.2 vs. 29.5 ± 4.6 kg/m2, P = 0.48). Intra-arterial infusion of phenylephrine (α1-agonist) and dexmedetomidine (α2-agonist) were used to induce vasoconstriction: [(FVCwith drug - FVCpredrug)/FVCpredrug × 100%]. Subjects completed rest and dynamic handgrip exercise (20% of maximum) trials per α-agonist. Patients with T2DM had smaller increases (Δ from rest) in FBF (147 ± 71 vs. 199 ± 63 ml/min) and FVC (126 ± 58 vs. 176 ± 50 ml·min-1·100 mmHg-1, P < 0.01 for both) during exercise compared with controls, respectively. During exercise, patients with T2DM had greater α1- (-16.9 ± 5.9 vs. -11.3 ± 3.8%) and α2-mediated vasoconstriction (-23.5 ± 7.1 vs. -19.0 ± 6.5%, P < 0.05 for both) versus controls. The magnitude of sympatholysis (Δ in %vasoconstriction between exercise and rest) for PE was lower (worse) in patients with T2DM versus controls (14.9 ± 12.2 vs. 23.1 ± 8.1%, P < 0.05) whereas groups were similar during DEX trials (24.6 ± 12.3 vs. 27.6 ± 13.4%, P = 0.47). Our data suggest patients with T2DM have attenuated hyperemic and vasodilatory responses to exercise, which could be attributable to greater α1-mediated vasoconstriction in contracting skeletal muscle.NEW & NOTEWORTHY Findings presented in this article are the first to show patients with type 2 diabetes mellitus have blunted hyperemic and vasodilatory responses to dynamic handgrip exercise. Moreover, we illustrate greater α1-adrenergic-mediated vasoconstriction may contribute to our initial observations. Collectively, these data suggest patients with type 2 diabetes may have impaired functional sympatholysis, which can contribute to their reduced exercise capacity.

Intermittent hypoxia enhances shear-mediated dilation of the internal carotid artery in young adults.

Cyclic intermittent hypoxia (IH) increases cerebral blood velocity. This enhanced velocity augments the commensurate shear stimulus and may subsequently increase cerebrovascular endothelial function. This study aimed to examine the effects of cyclic IH on hypercapnia-induced shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation was measured in nine adults (22 ± 4 yr) before as well as after 50 min of cyclic IH [5 cycles, 4 min of normoxia, followed by 6 min of hypoxia (target 80% [Formula: see text]) per cycle] and control normoxia (sham, 50 min of continuous normoxia) on separate days (≥72 h apart). ICA diameter and velocity were measured using Doppler ultrasound during cyclic IH and hypercapnia. Shear-mediated dilation was induced by 3 min of hypercapnia (Δ[Formula: see text]; IH: pre 10.1 ± 1.0 mmHg, post 10.8 ± 1.3 mmHg; sham: pre 10.5 ± 1.5 mmHg, post 10.8 ± 1.5 mmHg) and was calculated as the percent rise in peak relative to baseline diameter. Hypoxia increased ICA blood flow and shear rate (SR) during each cycle [blood flow: 322 ± 90 to 406 ± 74 mL/min, P < 0.01; SR: 179 ± 42 to 207 ± 55/s, P = 0.06, baseline to hypoxia (average of last minute of each cycle)], which was normalized during the succeeding normoxic period (blood flow: 322 ± 90 to 329 ± 68 mL/min, P = 0.54, SR: 179 ± 42 to 176 ± 32/s, P = 0.56). As such, shear-mediated dilation increased following cyclic IH (4.6 ± 1.3% to 6.2 ± 2.2%, P < 0.01), but not control normoxia (4.9 ± 1.4% to 4.9 ± 1.4%, P = 0.92). Our data indicate that increased blood flow and SR during cyclic IH enhance shear-mediated dilation of the ICA in young adults. These results suggest that cyclic IH could be used to optimize cerebral vascular health.NEW & NOTEWORTHY We explored the effects of cyclic intermittent hypoxia (IH) on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebral endothelial function, in young adults. Cyclic IH increased blood flow and shear rate in the ICA and, as a result, increased shear-mediated dilation of the ICA. These data suggest that cyclic IH could potentially be applied as a nonpharmacological therapy to optimize cerebral vascular health.

Aerobic exercise offsets endothelial dysfunction induced by repetitive consumption of sugar-sweetened beverages in young healthy men.

Consumption of a single, sugar-sweetened beverage (SSB) impairs vascular endothelial function. Regular aerobic exercise improves endothelium-dependent vasodilation; however, it is unknown whether these beneficial effects persist with frequent SSB consumption. Therefore, the purpose of this study was twofold; we studied the effects of repetitive SSB consumption (75 g d-glucose, 3 times/day) for 1 wk (Glu, n = 13, 23 ± 4 yr, 23.5 ± 3.4 kg/m2) on endothelium-dependent vasodilation (FMD). Then, in a separate cohort, we investigated whether 45 min of moderate-intensity aerobic exercise on five separate days offset the hypothesized decrease in FMD during the Glu protocol (Glu+Ex, n = 11, 21 ± 3 yr, 23.8 ± 2.4 kg/m2). Baseline, fasting [glucose] (P = 0.15), [insulin] (P = 0.25), %FMD (P = 0.48), absolute FMD (P = 0.66), and shear rate area under the curve (SRAUC; P = 0.82) were similar between groups. Following the interventions, fasting [glucose] (Glu: 94 ± 6 to 92 ± 6 mg/dL, Glu+Ex: 89 ± 8 to 87 ± 6 mg/dL, P = 0.74) and [insulin] (Glu: 11.3 ± 6.2 to 11.8 ± 8.9 µU/mL, Glu+Ex: 8.7 ± 2.9 to 9.4 ± 3.2 µU/mL, P = 0.89) were unchanged. %FMD was reduced in Glu (6.1 ± 2.2 to 5.1 ± 1.3%) and increased in Glu+Ex (6.6 ± 2.2 to 7.8 ± 2.4%, P < 0.05 for both). SRAUC increased similarly in both Glu [17,715 ± 8,275 to 22,922 ± 4,808 arbitrary units (A.U.)] and Glu+Ex (18,216 ± 4,516 to 21,666 ± 5,392 A.U., main effect of time P < 0.05). When %FMD was adjusted for SRAUC, attenuation was observed in Glu (0.41 ± 0.18 to 0.23 ± 0.08%/s × 103, P < 0.05) but not Glu+Ex (0.38 ± 0.14 to 0.38 ± 0.13%/s × 103, P = 0.88). Despite unchanged fasting [glucose] and [insulin], repeated consumption of SSBs impaired conduit artery vascular endothelial function. Additionally, subjects who engaged in regular moderate-intensity aerobic exercise did not demonstrate the same SSB-induced endothelial dysfunction. Collectively, these data suggest aerobic exercise may offset the deleterious effects of repetitive SSB consumption.

Habitual cigarette smoking attenuates shear-mediated dilation in the brachial artery but not in the carotid artery in young adults.

In the present study, we hypothesized that habitual cigarette smoking attenuates endothelial function in the cerebral circulation as well as that of the peripheral circulation in young adults. To test this hypothesis, we measured cerebrovascular and peripheral flow-mediated dilation (FMD) in young smokers and nonsmokers in the present study. Ten healthy nonsmokers and 10 smokers participated in the study. We measured blood velocity and diameter in the brachial artery and internal carotid artery (ICA) using Doppler ultrasound. We identified shear-mediated dilation in the brachial artery and ICA by the percentage change in peak diameter during hyperemia stimulation (reactive hyperemia and hypercapnia). We measured the baseline diameter and the shear rate area under the curve from the onset of hyperemia to peak dilation in the brachial artery and ICA, finding the measurements of the smokers and those of the nonsmokers did not differ (p > .05). In contrast to brachial FMD (5.07 ± 1.79% vs. 7.92 ± 3.01%; smokers vs. nonsmokers, p = .019), FMD in the ICA was not attenuated in the smokers compared with that of the nonsmokers (5.46 ± 2.32% vs. 4.57 ± 2.70%; p = .442). These findings indicate that in young healthy smokers, cerebral endothelial function was preserved, and the response of cerebral endothelial function to smoking was different from that of peripheral vasculature.

Acute hypotension attenuates brachial flow-mediated dilation in young healthy men.

PURPOSE: This study aimed to test our hypothesis that acute hypotension attenuates brachial flow-mediated dilation (FMD) as an index of endothelial function in healthy humans. METHODS: Twelve healthy men (21.8 ± 1.6 years, body mass index; 22.2 ± 1.6 kg/m2) participated in this study. Brachial FMD was measured in three trials: standardized FMD protocol (control trial), abrupt decrease in blood pressure (BP) via thigh cuff inflation-deflation (hypotension trial) and decrease in shear rate (SR) via a shortened forearm occlusion time (SR reduction trial). Brachial diameter and blood velocity were measured using Duplex ultrasound. RESULTS: Mean arterial pressure during reactive hyperaemia showed a marked decrease in the hypotension trial (- 23.7 ± 6.0 mmHg), but not in the control and SR reduction trials. SR area under the curve was attenuated in the SR reduction trial (P < 0.001), but not in the control and hypotension trials (P = 0.316). Consequently, FMD was attenuated in the hypotension and SR reduction trials compared with that in the control trial (P = 0.003 and P = 0.043, respectively), and was attenuated to a greater extent in the hypotension trial compared with the SR reduction trial (P = 0.006; control, 6.9 ± 3.5%; hypotension, 3.5 ± 1.7%; SR reduction, 5.0 ± 2.2%). After adjusting FMD using SR, FMD remained attenuated in the hypotension trial (P = 0.014), but not in the SR reduction trial. CONCLUSION: Our findings indicate that arterial pressure as well as sympathetic nervous system activation could be an important determinant of FMD. Blunted FMD of peripheral arteries may be a rational response to restore BP and/or prevent further reduction of BP following acute hypotension in healthy humans.

Effects of Respiratory Muscle Endurance Training in Hypoxia on Running Performance.

PURPOSE: We hypothesized that respiratory muscle endurance training (RMET) in hypoxia induces greater improvements in respiratory muscle endurance with attenuated respiratory muscle metaboreflex and consequent whole-body performance. We evaluated respiratory muscle endurance and cardiovascular response during hyperpnoea and whole-body running performance before and after RMET in normoxia and hypoxia. METHODS: Twenty-one collegiate endurance runners were assigned to control (n = 7), normoxic (n = 7), and hypoxic (n = 7) groups. Before and after the 6 wk of RMET, incremental respiratory endurance test and constant exercise tests were performed. The constant exercise test was performed on a treadmill at 95% of the individual's peak oxygen uptake (V˙O2peak). The RMET was isocapnic hyperpnoea under normoxic and hypoxic conditions (30 min·d). The initial target of minute ventilation during RMET was set to 50% of the individual maximal voluntary ventilation, and the target increased progressively during the 6 wk. Target arterial oxygen saturation in the hypoxic group was set to 90% in the first 2 wk, and thereafter it was set to 80%. RESULTS: Respiratory muscle endurance was increased after RMET in the normoxic and hypoxic groups. The time to exhaustion at 95% V˙O2peak exercise also increased after RMET in the normoxic (10.2 ± 2.4 to 11.2 ± 2.6 min) and hypoxic (11.5 ± 2.6 to 12.6 ± 3.0 min) groups, but not in the control group (9.6 ± 3.2 to 9.4 ± 4.0 min). The magnitude of these changes did not differ between the normoxic and the hypoxic groups (P = 0.84). CONCLUSION: These results suggest that the improvement of respiratory muscle endurance and blunted respiratory muscle metaboreflex could, in part, contribute to improved endurance performance in endurance-trained athletes. However, it is also suggested that there are no additional effects when the RMET is performed in hypoxia.

Neuromuscular electrical stimulation increases serum brain-derived neurotrophic factor in humans.

Brain-derived neurotrophic factor (BDNF) plays several important roles in nervous system function including neuronal growth and plasticity. The purpose of the present study was to clarify whether neuromuscular electrical stimulation (NMES) and voluntary exercise to the same integrated force as by the NMES-induced exercise would enhance serum BDNF. Eleven healthy male subjects completed three interventions (NMES, voluntary exercise, and resting interventions) for 20 min on different days. In the NMES intervention, NMES was applied to the quadriceps femoris muscles. The stimulus intensity of NMES was progressively increased to the highest tolerated intensity during the experiment. In the voluntary exercise intervention, subjects performed an isometric knee-extension task; in this intervention, the target torque was calculated in accordance with the integrated force of knee extension obtained during the NMES intervention. In the resting intervention, subjects relaxed in a sitting posture. We measured serum BDNF, blood lactate, heart rate, oxygen uptake, respiratory ratio, and blood pressure. Serum BDNF was increased in the NMES (p = 0.003) and voluntary exercise interventions (p = 0.004) after each intervention. At the post-timepoint, serum BDNF in the NMES intervention was highest among all interventions (p = 0.038) and significantly higher than in the voluntary exercise (p = 0.036) and resting (p = 0.037) interventions. Our results showed that NMES was more effective for enhancing serum BDNF than voluntary exercise at least when employing the same method and integrated force.

Hypercapnia-induced shear-mediated dilation in the internal carotid artery is blunted in healthy older adults.

This study aimed to elucidate the effect of aging on shear-mediated dilation of the common and internal carotid arteries (CCA and ICA, respectively). Hypercapnia-induced shear-mediated dilation in the CCA and ICA were assessed in 10 young (5 women and 5 men, 23 ± 1 yr) and 10 older (6 women/4 men, 68 ± 1 yr) healthy adults. Shear-mediated dilation was induced by two levels of hypercapnia (target end-tidal Pco2, +5 and +10 mmHg from individual baseline values) and was calculated as the percent rise in peak diameter from baseline diameter. There were no differences in shear-mediated dilation between young and older adults in either artery under lower levels of hypercapnia (CCA: 2.8 ± 0.6 vs. 2.0 ± 0.3%, P = 0.35; ICA: 4.6 ± 0.8 vs 3.6 ± 0.4%, P = 0.37). However, shear-mediated dilation in response to higher levels of hypercapnia was attenuated in older compared with young adults in the ICA (4.5 ± 0.5 vs. 7.9 ± 1.2%, P < 0.01) but not in the CCA (3.7 ± 0.6 vs. 4.5 ± 0.8%, P = 0.35). Shear-mediated dilation was significantly correlated to the percent change in shear rate in the ICA (young: r = 0.55, P = 0.01; older: r = 0.49, P = 0.03) but not in the CCA in either young or older adults (young: r = -0.30, P = 0.90; older: r = 0.16, P = 0.50). These data indicate that aging attenuates shear-mediated dilation of the ICA in response to higher levels of hypercapnia, and shear rate is an important stimulus for hypercapnic vasodilation of the ICA in both young and older adults. The present results may provide insights into age-related changes in the regulation of cerebral circulation in healthy adults. NEW & NOTEWORTHY We explored the effect of aging on shear-mediated dilation in the common and internal carotid arteries (CCA and ICA, respectively) in healthy adults. Our findings suggest that 1) aging attenuates shear-mediated dilation of the ICA but not the CCA and 2) shear rate is an important stimulus for hypercapnic vasodilation of the ICA in young and older adults. These findings may provide insights into the age-related changes in cerebrovascular regulation of healthy adults.