Functional OCT reveals anisotropic changes of retinal flicker-evoked vasodilation.

The purpose of this study is to verify the effect of anisotropic property of retinal biomechanics on vasodilation measurement. A custom-built optical coherence tomography (OCT) was used for time-lapse imaging of flicker stimulation-evoked vessel lumen changes in mouse retinas. A comparative analysis revealed significantly larger (18.21%) lumen dilation in the axial direction compared to the lateral (10.77%) direction. The axial lumen dilation predominantly resulted from the top vessel wall movement toward the vitreous direction, whereas the bottom vessel wall remained stable. This observation indicates that the traditional vasodilation measurement in the lateral direction may result in an underestimated value.

Inhibition of superoxide and iNOS augment cutaneous nitric oxide-dependent vasodilation in non-Hispanic black young adults.

We assessed the combined effect of superoxide and iNOS inhibition on microvascular function in non-Hispanic Black and non-Hispanic White participants (n = 15 per group). Participants were instrumented with four microdialysis fibers: (1) lactated Ringer's (control), (2) 10 µM tempol (superoxide inhibition), (3) 0.1 mM 1400 W (iNOS inhibition), (4) tempol + 1400 W. Cutaneous vasodilation was induced via local heating and NO-dependent vasodilation was quantified. At control sites, NO-dependent vasodilation was lower in non-Hispanic Black (45 ± 9% NO) relative to non-Hispanic White (79 ± 9% NO; p < 0.01; effect size, d = 3.78) participants. Tempol (62 ± 16% NO), 1400 W (78 ± 12% NO) and tempol +1400 W (80 ± 13% NO) increased NO-dependent vasodilation in non-Hispanic Black participants relative to control sites (all p < 0.01; d = 1.22, 3.05, 3.03, respectively). The effect of 1400 W (p = 0.04, d = 1.11) and tempol +1400 W (p = 0.03, d = 1.22) was greater than tempol in non-Hispanic Black participants. There was no difference between non-Hispanic Black and non-Hispanic White participants at 1400 W or tempol + 1400 W sites. These data suggest iNOS has a greater effect on NO-dependent vasodilation than superoxide in non-Hispanic Black participants.

Excessive hypercholesterolemia in pregnancy impairs rat uterine artery function via activation of Toll-like receptor 4.

Hypercholesterolemia in pregnancy is a physiological process required for normal fetal development. In contrast, excessive pregnancy-specific hypercholesterolemia increases the risk of complications, such as preeclampsia. However, the underlying mechanisms are unclear. Toll-like receptor 4 (TLR4) is a membrane receptor modulated by high cholesterol levels, leading to endothelial dysfunction; but whether excessive hypercholesterolemia in pregnancy activates TLR4 is not known. We hypothesized that a high cholesterol diet (HCD) during pregnancy increases TLR4 activity in uterine arteries, leading to uterine artery dysfunction. Sprague Dawley rats were fed a control diet (n=12) or HCD (n=12) during pregnancy (gestational day 6-20). Vascular function was assessed in main uterine arteries using wire myography (vasodilation to methacholine and vasoconstriction to phenylephrine; with and without inhibitors for mechanistic pathways) and pressure myography (biomechanical properties). Exposure to a HCD during pregnancy increased maternal blood pressure, induced proteinuria, and reduced the fetal-to-placental weight ratio for both sexes. Excessive hypercholesterolemia in pregnancy also impaired vasodilation to methacholine in uterine arteries, whereby at higher doses, methacholine caused vasoconstriction instead of vasodilation in only the HCD group, which was prevented by inhibition of TLR4 or prostaglandin H synthase 1. Endothelial nitric oxide synthase expression and nitric oxide levels were reduced in HCD compared with control dams. Vasoconstriction to phenylephrine and biomechanical properties were similar between groups. In summary, excessive hypercholesterolemia in pregnancy impairs uterine artery function, with TLR4 activation as a key mechanism. Thus, TLR4 may be a target for therapy development to prevent adverse perinatal outcomes in complicated pregnancies.

Observations of cold-induced vasodilation in persons with spinal cord injuries.

STUDY DESIGN: Acute experimental study. OBJECTIVES: Cold-induced vasodilation is a local mechanism of protection against frostbite in non-injured persons. We assessed whether an increase in skin blood flow (SkBF) during local cooling (LC) was observed in individuals with spinal cord injuries (SCIs) and if the response patterns differed between region levels or sites. SETTING: Laboratory of Wakayama Medical University and the affiliated clinics, Japan. METHODS: A local cooler device (diameter 4 cm) was placed on the chest (sensate) and right thigh (non-sensate) in persons with cervical (SCIC; n = 9) and thoracolumbar SCIs (SCITL; n = 9). After the surface temperature under the device was controlled at 33 °C for 10 min (baseline), LC (-0.045 °C/s) was applied and the skin temperature was maintained at 15 and 8 °C for 15 min of each stage. SkBF (laser Doppler flowmetry) was monitored using a 1-mm needle-type probe inserted into its center. RESULTS: The percent change in SkBF (%ΔSkBF) on the chest remained unchanged until the end of 15 °C stage; thereafter, it increased to a level at least 70% greater than the baseline during the 8 °C stage in both groups. The %ΔSkBF on the thigh in both SCIC and SCITL notably increased from 8 and 6 min respectively, during the 8°C stage, compared to 1 min before the stage; however, it did not exceed the baseline level. CONCLUSIONS: An increase in SkBF during LC was observed both in the sensate and non-sensate areas in SCIs, although the magnitude was larger in the sensate area.

Acute inspiratory resistance training enhances endothelium-dependent dilation and retrograde shear rate in healthy young adults.

Inspiratory resistance training (IRT) yields significant reductions in resting blood pressure and improves vascular endothelial function. Our objective was to quantify the acute effects of IRT on brachial artery flow-mediated dilation (FMD) and shear rates (SRs) in healthy men and women. Twenty young adults (22.9 ± 3.4 years; 10 male, 10 female) completed a single bout of IRT or Rest condition in a randomized crossover design. Brachial artery FMD was performed before, 10 min after, and 40 min after the assigned condition. Brachial artery blood flow velocities were collected during IRT, separated by breathing cycle phase, and converted into SRs. FMD improved 10 min post-IRT (+1.86 ± 0.61%; p = 0.025) but returned to baseline by 40 min post-IRT (p = 0.002). Anterograde SR decreased by 10% and retrograde SR increased 102% during resisted inspiration, relative to baseline SR (p < 0.001). Anterograde SR increased by 7% in men and women (p < 0.001) and retrograde SR decreased by 12% in women but not men (p = 0.022) during unresisted expiration, relative to baseline SR. A single bout of IRT elicits a transient enhancement in FMD in both men and women. Acute IRT-related enhancements in SRs may contribute to sustained improvements in FMD that have been reported previously.

Evidence of premature vascular dysfunction in young adults who regularly use e-cigarettes and the impact of usage length.

BACKGROUND: Electronic (e-) cigarettes are increasingly popular tobacco products on the US market. Traditional tobacco products are known to cause vascular dysfunction, one of the earliest indicators of cardiovascular disease (CVD) development. However, little is known about the effect of regular e-cigarette use on vascular function. The purpose of this study was to investigate the impact of regular e-cigarette use on vascular function and cardiovascular health in young, healthy adults. METHODS: Twenty-one regular users of e-cigarettes (ECU) and twenty-one demographically matched non-users (NU) completed this study. Vascular health was assessed in the cutaneous microcirculation through different reactivity tests to evaluate overall functionality, endothelium-dependent vasodilation (EDD), and endothelium-independent vasodilation (EID). Macrovascular function was assessed using flow-mediated dilation (FMD). RESULTS: Our results suggest that regular users of e-cigarettes present with premature microvascular impairment when compared to non-users. Specifically, they exhibit lower hyperemic (p = 0.003), thermal (p = 0.010), and EDD (p = 0.004) responses. No differences in EID between the groups were identified. We also identified that individuals who use e-cigarettes for longer than 3 years also present with systemic manifestations, as observed by significantly reduced macrovascular (p = 0.002) and microvascular (p ≤ 0.044) function. CONCLUSIONS: Our novel data suggests that young, apparently healthy, regular users of e-cigarettes present with premature vascular dysfunction in the microcirculation when compared to non-users. We have also identified systemic vascular dysfunction affecting both the micro and macrovasculature in those young individuals who used e-cigarettes for longer than 3 years. Taken together, these findings associate regular e-cigarette use with premature vascular dysfunctions and adverse cardiovascular outcomes.

Statin administration improves vascular function in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by impaired vascular endothelial function that may be improved by hydroxy-methylglutaryl-CoA (HMG-CoA) reductase enzyme inhibition. Thus, using a parallel, double-blind, placebo-controlled design, this study evaluated the efficacy of 30-day atorvastatin administration (10 mg daily) on peripheral vascular function and biomarkers of inflammation and oxidative stress in 16 patients with HFpEF [Statin: n = 8, 74 ± 6 yr, ejection fraction (EF) 52-73%; Placebo: n = 8, 67 ± 9 yr, EF 56-72%]. Flow-mediated dilation (FMD) and sustained-stimulus FMD (SS-FMD) during handgrip (HG) exercise, reactive hyperemia (RH), and blood flow during HG exercise were evaluated to assess conduit vessel function, microvascular function, and exercising muscle blood flow, respectively. FMD improved following statin administration (pre, 3.33 ± 2.13%; post, 5.23 ± 1.35%; P < 0.01), but was unchanged in the placebo group. Likewise, SS-FMD, quantified using the slope of changes in brachial artery diameter in response to increases in shear rate, improved following statin administration (pre: 5.31e-5 ± 3.85e-5 mm/s-1; post: 8.54e-5 ± 4.98e-5 mm/s-1; P = 0.03), with no change in the placebo group. Reactive hyperemia and exercise hyperemia responses were unchanged in both statin and placebo groups. Statin administration decreased markers of lipid peroxidation (malondialdehyde, MDA) (pre, 0.652 ± 0.095; post, 0.501 ± 0.094; P = 0.04), whereas other inflammatory and oxidative stress biomarkers were unchanged. Together, these data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular function or exercising limb blood flow, in patients with HFpEF, which may be due in part to reductions in oxidative stress.NEW & NOTEWORTHY This is the first study to investigate the impact of statin administration on vascular function and exercise hyperemia in patients with heart failure with preserved ejection fraction (HFpEF). In support of our hypothesis, both conventional flow-mediated dilation (FMD) testing and brachial artery vasodilation in response to sustained elevations in shear rate during handgrip exercise increased significantly in patients with HFpEF following statin administration, beneficial effects that were accompanied by a decrease in biomarkers of oxidative damage. However, contrary to our hypothesis, reactive hyperemia and exercise hyperemia were unchanged in patients with HFpEF following statin therapy. These data provide new evidence for the efficacy of low-dose statin administration to improve brachial artery endothelium-dependent vasodilation, but not microvascular reactivity or exercising muscle blood flow in patients with HFpEF, which may be due in part to reductions in oxidative stress.

Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling.

Neurovascular coupling (NVC) is important for brain function and its dysfunction underlies many neuropathologies. Although cell-type specificity has been implicated in NVC, how active neural information is conveyed to the targeted arterioles in the brain remains poorly understood. Here, using two-photon focal optogenetics in the mouse cerebral cortex, we demonstrate that single glutamatergic axons dilate their innervating arterioles via synaptic-like transmission between neural-arteriolar smooth muscle cell junctions (NsMJs). The presynaptic parental-daughter bouton makes dual innervations on postsynaptic dendrites and on arteriolar smooth muscle cells (aSMCs), which express many types of neuromediator receptors, including a low level of glutamate NMDA receptor subunit 1 (Grin1). Disruption of NsMJ transmission by aSMC-specific knockout of GluN1 diminished optogenetic and whisker stimulation-caused functional hyperemia. Notably, the absence of GluN1 subunit in aSMCs reduced brain atrophy following cerebral ischemia by preventing Ca2+ overload in aSMCs during arteriolar constriction caused by the ischemia-induced spreading depolarization. Our findings reveal that NsMJ transmission drives NVC and open up a new avenue for studying stroke.

Role of Protein Kinase C in Metabolic Regulation of Coronary Endothelial Small Conductance Calcium-Activated Potassium Channels.

BACKGROUND: Small conductance calcium-activated potassium (SK) channels are largely responsible for endothelium-dependent coronary arteriolar relaxation. Endothelial SK channels are downregulated by the reduced form of nicotinamide adenine dinucleotide (NADH), which is increased in the setting of diabetes, yet the mechanisms of these changes are unclear. PKC (protein kinase C) is an important mediator of diabetes-induced coronary endothelial dysfunction. Thus, we aimed to determine whether NADH signaling downregulates endothelial SK channel function via PKC. METHODS AND RESULTS: SK channel currents of human coronary artery endothelial cells were measured by whole cell patch clamp method in the presence/absence of NADH, PKC activator phorbol 12-myristate 13-acetate, PKC inhibitors, or endothelial PKCα/PKCß knockdown by using small interfering RNA. Human coronary arteriolar reactivity in response to the selective SK activator NS309 was measured by vessel myography in the presence of NADH and PKCß inhibitor LY333531. NADH (30-300 µmol/L) or PKC activator phorbol 12-myristate 13-acetate (30-300 nmol/L) reduced endothelial SK current density, whereas the selective PKCᵦ inhibitor LY333531 significantly reversed the NADH-induced SK channel inhibition. PKCß small interfering RNA, but not PKCα small interfering RNA, significantly prevented the NADH- and phorbol 12-myristate 13-acetate-induced SK inhibition. Incubation of human coronary artery endothelial cells with NADH significantly increased endothelial PKC activity and PKCß expression and activation. Treating vessels with NADH decreased coronary arteriolar relaxation in response to the selective SK activator NS309, and this inhibitive effect was blocked by coadministration with PKCß inhibitor LY333531. CONCLUSIONS: NADH-induced inhibition of endothelial SK channel function is mediated via PKCß. These findings may provide insight into novel therapeutic strategies to preserve coronary microvascular function in patients with metabolic syndrome and coronary disease.

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

Sauna has been linked to a reduction of cardiovascular disease risk and is a promising nonpharmacological treatment for populations at risk of cardiovascular disease. This study examined the vascular response to an acute bout of sauna heating in young and middle-aged individuals. Ten young (25 ± 4 yr, 6 males and 4 females) and eight middle-aged adults (56 ± 4 yr, 4 males and 4 females) underwent 40 min of sauna exposure at 80°C. Esophageal and intramuscular temperatures, brachial and superficial femoral artery blood flow, artery diameter, and shear rates were recorded at baseline and following heat exposure. Brachial artery flow-mediated dilation (FMD) was measured at baseline and following 90 min of recovery. Esophageal and muscle temperatures increased similarly in the young and middle-aged adults by 1.5 ± 0.53 and 1.95 ± 0.70°C, respectively (P < 0.05). The shear rate increased by 170-200% (P < 0.001), while blood flow increased by 180-390% (P < 0.001) in the superficial femoral and brachial arteries, respectively, and did not differ between age groups (P = 0.190-0.899). Systolic blood pressure was reduced from 135 ± 17 to 122 ± 20 mmHg (P = 0.017) in middle-aged participants. These data indicate that young and middle-aged adults have similar vascular responses to acute sauna heating.NEW & NOTEWORTHY Sauna therapy has been shown to improve cardiovascular health and function in older adults and individuals with cardiovascular disease risk factors. Specifically, improvements in vascular function have been reported and have been attributed to the increased hemodynamic stimuli on the vasculature associated with thermal stress. The present study quantified this hemodynamic response to a sauna protocol associated with improved cardiovascular health across the lifespan. Our data show that middle-aged adults have the same shear rate and blood flow response to sauna as young adults.

Elevated blood flow in people with type 1 and type 2 diabetes.

AIMS: The study aimed to evaluate blood flow (BF) and microvascular function in the forearm of people with type 1 and type 2 diabetes at rest and after ischemia. Microvascular function plays a crucial role in regulating BF in peripheral tissues based on metabolic demand. METHODS: People with diabetes and sex-matched healthy controls were recruited. Brachial artery diameter and blood velocity were continuously measured at rest and after ischemia by an automatic tracking system. BF and vascular conductance were then calculated. RESULTS: Forty-nine people with diabetes and 49 controls were enrolled. BF at rest and after ischemia was significantly higher in people with diabetes than controls: Type 1, 243 ± 116 and 631 ± 233 ml/min; controls, 180 ± 106 and 486 ± 227 ml/min; Type 2, 332 ± 149 and 875 ± 293 ml/min; controls 222 ± 106 and 514 ± 224 ml/min. Vascular conductance was significantly higher in Type 2 than in controls at rest and after ischemia. CONCLUSIONS: People with diabetes exhibited significantly increased BF, with Type 2 also showing heightened vascular conductance. Activating metabolic pathways triggered by hyperglycemia may lead to distinct vascular redistribution, potentially impairing blood flow over time. These findings of the study underscore the importance of understanding overall vascular dynamics in diabetes and its implications for vascular health.

The conducted vascular response as a mediator of hypercapnic cerebrovascular reactivity: A modelling study.

It is well established that the cerebral blood flow (CBF) shows exquisite sensitivity to changes in the arterial blood partial pressure of CO2 ( [Formula: see text] ), which is reflected by an index termed cerebrovascular reactivity. In response to elevations in [Formula: see text] (hypercapnia), the vessels of the cerebral microvasculature dilate, thereby decreasing the vascular resistance and increasing CBF. Due to the challenges of access, scale and complexity encountered when studying the microvasculature, however, the mechanisms behind cerebrovascular reactivity are not fully understood. Experiments have previously established that the cholinergic release of the Acetylcholine (ACh) neurotransmitter in the cortex is a prerequisite for the hypercapnic response. It is also known that ACh functions as an endothelial-dependent agonist, in which the local administration of ACh elicits local hyperpolarization in the vascular wall; this hyperpolarization signal is then propagated upstream the vascular network through the endothelial layer and is coupled to a vasodilatory response in the vascular smooth muscle (VSM) layer in what is known as the conducted vascular response (CVR). Finally, experimental data indicate that the hypercapnic response is more strongly correlated with the CO2 levels in the tissue than in the arterioles. Accordingly, we hypothesize that the CVR, evoked by increases in local tissue CO2 levels and a subsequent local release of ACh, is responsible for the CBF increase observed in response to elevations in [Formula: see text] . By constructing physiologically grounded dynamic models of CBF and control in the cerebral vasculature, ones that integrate the available knowledge and experimental data, we build a new model of the series of signalling events and pathways underpinning the hypercapnic response, and use the model to provide compelling evidence that corroborates the aforementioned hypothesis. If the CVR indeed acts as a mediator of the hypercapnic response, the proposed mechanism would provide an important addition to our understanding of the repertoire of metabolic feedback mechanisms possessed by the brain and would motivate further in-vivo investigation. We also model the interaction of the hypercapnic response with dynamic cerebral autoregulation (dCA), the collection of mechanisms that the brain possesses to maintain near constant CBF despite perturbations in pressure, and show how the dCA mechanisms, which otherwise tend to be overlooked when analysing experimental results of cerebrovascular reactivity, could play a significant role in shaping the CBF response to elevations in [Formula: see text] . Such in-silico models can be used in tandem with in-vivo experiments to expand our understanding of cerebrovascular diseases, which continue to be among the leading causes of morbidity and mortality in humans.

Single-Cell RNA-Seq Reveals Coronary Heterogeneity and Identifies CD133+TRPV4high Endothelial Subpopulation in Regulating Flow-Induced Vascular Tone in Mice.

BACKGROUND: Single-cell RNA-Seq analysis can determine the heterogeneity of cells between different tissues at a single-cell level. Coronary artery endothelial cells (ECs) are important to coronary blood flow. However, little is known about the heterogeneity of coronary artery ECs, and cellular identity responses to flow. Identifying endothelial subpopulations will contribute to the precise localization of vascular endothelial subpopulations, thus enabling the precision of vascular injury treatment. METHODS: Here, we performed a single-cell RNA sequencing of 31 962 cells and functional assays of 3 branches of the coronary arteries (right coronary artery/circumflex left coronary artery/anterior descending left coronary artery) in wild-type mice. RESULTS: We found a compendium of 7 distinct cell types in mouse coronary arteries, mainly ECs, granulocytes, cardiac myocytes, smooth muscle cells, lymphocytes, myeloid cells, and fibroblast cells, and showed spatial heterogeneity between arterial branches. Furthermore, we revealed a subpopulation of coronary artery ECs, CD133+TRPV4high ECs. TRPV4 (transient receptor potential vanilloid 4) in CD133+TRPV4high ECs is important for regulating vasodilation and coronary blood flow. CONCLUSIONS: Our study elucidates the nature and range of coronary arterial cell diversity and highlights the importance of coronary CD133+TRPV4high ECs in regulating coronary vascular tone.

Sitting leg vasculopathy: potential adaptations beyond the endothelium.

Increased sitting time, the most common form of sedentary behavior, is an independent risk factor for all-cause and cardiovascular disease mortality; however, the mechanisms linking sitting to cardiovascular risk remain largely elusive. Studies over the last decade have led to the concept that excessive time spent in the sitting position and the ensuing reduction in leg blood flow-induced shear stress cause endothelial dysfunction. This conclusion has been mainly supported by studies using flow-mediated dilation in the lower extremities as the measured outcome. In this review, we summarize evidence from classic studies and more recent ones that collectively support the notion that prolonged sitting-induced leg vascular dysfunction is likely also attributable to changes occurring in vascular smooth muscle cells (VSMCs). Indeed, we provide evidence that prolonged constriction of resistance arteries can lead to modifications in the structural characteristics of the vascular wall, including polymerization of actin filaments in VSMCs and inward remodeling, and that these changes manifest in a time frame that is consistent with the vascular changes observed with prolonged sitting. We expect this review will stimulate future studies with a focus on VSMC cytoskeletal remodeling as a potential target to prevent the detrimental vascular ramifications of too much sitting.

Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction.

Systemic inhibition of the mammalian target of rapamycin (mTOR) delays aging and many age-related conditions including arterial and metabolic dysfunction. However, the mechanisms and tissues involved in these beneficial effects remain largely unknown. Here, we demonstrate that activation of S6K, a downstream target of mTOR, is increased in arteries with advancing age, and that this occurs preferentially in the endothelium compared with the vascular smooth muscle. Induced endothelial cell-specific deletion of mTOR reduced protein expression by 60-70%. Although this did not significantly alter arterial and metabolic function in young mice, endothelial mTOR reduction reversed arterial stiffening and improved endothelium-dependent dilation (EDD) in old mice, indicating an improvement in age-related arterial dysfunction. Improvement in arterial function in old mice was concomitant with reductions in arterial cellular senescence, inflammation, and oxidative stress. The reduction in endothelial mTOR also improved glucose tolerance in old mice, and this was associated with attenuated hepatic gluconeogenesis and improved lipid tolerance, but was independent of alterations in peripheral insulin sensitivity, pancreatic beta cell function, or fasted plasma lipids in old mice. Lastly, we found that endothelial mTOR reduction suppressed gene expression of senescence and inflammatory markers in endothelial-rich (i.e., lung) and metabolically active organs (i.e., liver and adipose tissue), which may have contributed to the improvement in metabolic function in old mice. This is the first evidence demonstrating that reducing endothelial mTOR in old age improves arterial and metabolic function. These findings have implications for future drug development.

Cold-induced vasodilation during sequential immersions of the hand.

A common practice for those operating in cold environments includes repetitive glove doffing and donning to perform specific tasks, which creates a repetitive cycle of hand cooling and rewarming. This study aimed to determine the influence of intraday repeated hand cooling on cold-induced vasodilation (CIVD), sympathetic activation, and finger/hand temperature recovery. Eight males and two females (mean ± SD age: 28 ± 5 year; height: 181 ± 9 cm; weight: 79.9 ± 10.4 kg) performed two 30-min hand immersions in cold (4.3 ± 0.92 °C) water in an indoor environment (18 °C). Both immersions (Imm1; Imm2) were performed on the same day and both allowed for a 10-min recovery. CIVD components were calculated for each finger (index, middle, ring) during each immersion. CIVD onset time (index, p = 0.546; middle, p = 0.727; ring, p = 0.873), minimum finger temperature (index, p = 0.634; middle, p = 0.493; ring, p = 0.575), and mean finger temperature (index, p = 0.986; middle, p = 0.953; ring, p = 0.637) were all similar between immersions. Recovery rates generally demonstrated similar responses as well. Findings suggest that two sequential CIVD tests analyzing the effect of prior cold exposure of the hand does not impair the CIVD response or recovery. Such findings appear promising for those venturing into cold environments where hands are likely to be repeatedly exposed to cold temperatures.

Interaction between local blood flow and tolerance to prolonged pain in the elderly.

PURPOSE: We aimed to explore the link between local vasodilation and pain perception in elderly subjects, testing the hypothesis that altered local cutaneous blood flow participates in the decrease in pain tolerance with age. METHOD: Sixty-eight young and 83 older participants performed a pain tolerance test in which they hold their hand in an airtight box in which air temperature was regulated at 65 °C until the pain became unbearable. Participants continuously estimated pain intensity. Skin temperature and local blood flow in the box-exposed hand were continuously monitored. RESULTS: In the young group, 97% of subjects resisted pain until the end of the test, whereas only 53% in the elderly group managed to do so, indicating that pain tolerance is impaired in the elderly. Among all participants, the skin temperature associated with the first pain sensation was below the threshold for nociceptor activation (43 °C). Interestingly, blood flow in the elderly group was correlated with pain judgment, whereas no such correlation was observed in the young. CONCLUSION: Our results suggest that the local vasodilator response induced by local heating may be involved in pain perception and may influence thermal pain tolerance with aging. These results could contribute to a better understanding of vascular deficits and the development of chronic pain in vascular pathologies.

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.

Obesity does not alter vascular function and handgrip exercise hemodynamics in middle-aged patients with hypertension.

Lifestyle modification including exercise training is often the first line of defense in the treatment of obesity and hypertension (HTN), however, little is known regarding how these potentially compounding disease states impact vasodilatory and hemodynamic responses at baseline and exercise. Therefore, this study sought to compare the impact of obesity on vascular function and hemodynamics at baseline and during handgrip (HG) exercise among individuals with HTN. Non-obese (13M/7F, 56 ± 16 yr, 25 ± 4 kg/m2) and obese (17M/4F, 50 ± 7 yr, 35 ± 4 kg/m2) middle-aged individuals with HTN forwent antihypertensive medication use for ≥2 wk before assessment of vascular function by brachial artery flow-mediated dilation (FMD) and exercise hemodynamics during progressive HG exercise at 15-30-45% maximal voluntary contraction (MVC). FMD was not different between Non-Obese (4.1 ± 1.7%) and Obese (5.2 ± 1.9%, P = 0.11). Systolic blood pressure (SBP) was elevated by ∼15% during the supine baseline and during HG exercise in the obese group. The blood flow response to HG exercise at 30% and 45% MVC was ∼20% greater (P < 0.05) in the obese group but not different after normalizing for the higher, albeit, nonsignificant differences in workloads (MVC: obese: 24 ± 5 kg, non-obese: 21 ± 5 kg, P = 0.11). Vascular conductance and the brachial artery shear-induced vasodilatory response during HG were not different between groups (P > 0.05). Taken together, despite elevated SBP during HG exercise, obesity does not lead to additional impairments in vascular function and peripheral exercising hemodynamics in patients with HTN. Obesity may not be a contraindication when prescribing exercise for the treatment of HTN among middle-aged adults, however, the elevated SBP should be appropriately monitored.NEW & NOTEWORTHY This study examined vascular function and handgrip exercise hemodynamics in obese and nonobese individuals with hypertension. Obesity, when combined with hypertension, was neither associated with additional vascular function impairments at baseline nor peripheral hemodynamics and vasodilation during exercise compared with nonobese hypertension. Interestingly, systolic blood pressure and pulse pressure were greater in the obese group during supine baseline and exercise. These findings should not be ignored and may be particularly important for rehabilitation strategies.

Nitric oxide-mediated vasodilation in human bone.

OBJECTIVE: Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone. METHODS: In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg. RESULTS: LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 µM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 µM) at 10 min (p = .01). CONCLUSIONS: In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.