Sympathetic Neural Control at Rest and During the Cold Pressor Test in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: We tested the hypothesis that patients with heart failure with preserved ejection fraction (HFpEF) would have greater muscle sympathetic nerve activity (MSNA) at rest and sympathetic reactivity during a cold pressor test compared with non-heart failure controls. Further, given the importance of the baroreflex modulation of MSNA in the control of blood pressure (BP), we hypothesized that patients with HFpEF would exhibit a reduced sympathetic baroreflex sensitivity. METHODS: Twenty-eight patients with HFpEF and 44 matched controls (mean±SD: 71±8 versus 70±7 years; 9 men/19 women versus 16 men/28 women) were studied. BP, heart rate, and MSNA (microneurography) were measured during 6 to 10 minutes of supine rest and the 2-minute cold pressor test. Spontaneous sympathetic baroreflex sensitivity was assessed during supine rest. RESULTS: Patients with HFpEF had higher resting MSNA burst frequency (39±14 versus 31±12 bursts/min; P=0.020) and lower sympathetic baroreflex sensitivity (-2.83±0.76 versus -3.57±1.19 bursts/100 heartbeats/mm Hg; P=0.019) than controls, but burst incidence was not different between groups (56±19 versus 50±20 bursts/100 heartbeats; P=0.179). During the cold pressor test, increases in MSNA indices did not differ between groups (P=0.135-0.998), but patients had a smaller increase in diastolic BP (Δ4±6 versus Δ14±11 mm Hg; P<0.001) compared with controls. CONCLUSIONS: Despite augmented resting MSNA burst frequency, burst incidence was not significantly different between groups, and sympathetic baroreflex sensitivity was reduced in patients with HFpEF. Furthermore, patients had preserved sympathetic reactivity but attenuated diastolic BP responses during the cold pressor test. These data suggest that, during physiological stress, sympathetic reactivity is intact, but the peripheral pathway for sympathetic vasoconstriction may be impaired in HFpEF.

Sympathetic and hemodynamic responses to exercise in heart failure with preserved ejection fraction.

Excessive sympathetic activity during exercise causes heightened peripheral vasoconstriction, which can reduce oxygen delivery to active muscles, resulting in exercise intolerance. Although both patients suffering from heart failure with preserved and reduced ejection fraction (HFpEF and HFrEF, respectively) exhibit reduced exercise capacity, accumulating evidence suggests that the underlying pathophysiology may be different between these two conditions. Unlike HFrEF, which is characterized by cardiac dysfunction with lower peak oxygen uptake, exercise intolerance in HFpEF appears to be predominantly attributed to peripheral limitations involving inadequate vasoconstriction rather than cardiac limitations. However, the relationship between systemic hemodynamics and the sympathetic neural response during exercise in HFpEF is less clear. This mini review summarizes the current knowledge on the sympathetic (i.e., muscle sympathetic nerve activity, plasma norepinephrine concentration) and hemodynamic (i.e., blood pressure, limb blood flow) responses to dynamic and static exercise in HFpEF compared to HFrEF, as well as non-HF controls. We also discuss the potential of a relationship between sympathetic over-activation and vasoconstriction leading to exercise intolerance in HFpEF. The limited body of literature indicates that higher peripheral vascular resistance, perhaps secondary to excessive sympathetically mediated vasoconstrictor discharge compared to non-HF and HFrEF, drives exercise in HFpEF. Excessive vasoconstriction also may primarily account for over elevations in blood pressure and concomitant limitations in skeletal muscle blood flow during dynamic exercise, resulting in exercise intolerance. Conversely, during static exercise, HFpEF exhibit relatively normal sympathetic neural reactivity compared to non-HF, suggesting that other mechanisms beyond sympathetic vasoconstriction dictate exercise intolerance in HFpEF.

The acute effect of whole-body heat therapy on peripheral and cerebral vascular reactivity in Black and White females.

Among females in the U.S., Black females suffer the most from cardiovascular disease and stroke. While the reasons for this disparity are multifactorial, vascular dysfunction likely contributes. Chronic whole-body heat therapy (WBHT) improves vascular function, but few studies have examined its acute effect on peripheral or cerebral vascular function, which may help elucidate chronic adaptative mechanisms. Furthermore, no studies have investigated this effect in Black females. We hypothesized that Black females would have lower peripheral and cerebral vascular function relative to White females and that one session of WBHT would mitigate these differences. Eighteen young, healthy Black (n = 9; 21 ± 3 yr; BMI: 24.7 ± 4.5 kg/m2) and White (n = 9; 27 ± 3 yr; BMI: 24.8 ± 4.1 kg/m2) females underwent one 60 min session of WBHT (49 °C water via a tube-lined suit). Pre- and 45 min post-testing measures included post-occlusive forearm reactive hyperemia (peripheral microvascular function, RH), brachial artery flow-mediated dilation (peripheral macrovascular function, FMD), and cerebrovascular reactivity (CVR) to hypercapnia. Prior to WBHT, there were no differences in RH, FMD, or CVR (p > 0.05 for all). WBHT improved peak RH in both groups (main effect of WBHT: 79.6 ± 20.1 cm/s to 95.9 ± 30.0 cm/s; p = 0.004, g = 0.787) but not Δ blood velocity (p > 0.05 for both groups). WBHT improved FMD in both groups (6.2 ± 3.4 % to 8.8 ± 3.7 %; p = 0.016, g = 0.618) but had no effect on CVR in either group (p = 0.077). These data indicate that one session of WBHT acutely improves peripheral micro- and macrovascular but not cerebral vascular function in Black and White females.

Effects of posture changes on dynamic cerebral autoregulation during early pregnancy in women with obesity and/or sleep apnea.

The incidence of syncope during orthostasis increases in early human pregnancy, which may be associated with cerebral blood flow (CBF) dysregulation in the upright posture. In addition, obesity and/or sleep apnea per se may influence CBF regulation due to their detrimental impacts on cerebrovascular function. However, it is unknown whether early pregnant women with obesity and/or sleep apnea could have impaired CBF regulation in the supine position and whether this impairment would be further exacerbated in the upright posture. Dynamic cerebral autoregulation (CA) was evaluated using transfer function analysis in 33 women during early pregnancy (13 with obesity, 8 with sleep apnea, 12 with normal weight) and 15 age-matched nonpregnant women during supine rest. Pregnant women also underwent a graded head-up tilt (30° and 60° for 6 min each). We found that pregnant women with obesity or sleep apnea had a higher transfer function low-frequency gain compared with nonpregnant women in the supine position (P = 0.026 and 0.009, respectively) but not normal-weight pregnant women (P = 0.945). Conversely, the transfer function low-frequency phase in all pregnancy groups decreased during head-up tilt (P = 0.001), but the phase was not different among pregnant groups (P = 0.180). These results suggest that both obesity and sleep apnea may have a detrimental effect on dynamic CA in the supine position during early pregnancy. CBF may be more vulnerable to spontaneous blood pressure fluctuations in early pregnant women during orthostatic stress compared with supine rest due to less efficient dynamic CA, regardless of obesity and/or sleep apnea.

Greater resting muscle sympathetic nerve activity reduces cold pressor autonomic reactivity in older women, but not older men.

Previous work demonstrates augmented muscle sympathetic nerve activity (MSNA) responses to the cold pressor test (CPT) in older women. Given its interindividual variability, however, the influence of baseline MSNA on CPT reactivity in older adults remains unknown. Sixty volunteers (60-83y; 30 women) completed testing where MSNA (microneurography), blood pressure (BP), and heart rate (HR) were recorded during baseline and a 2-min CPT (~4°C). Participant data were terciled by baseline MSNA (n=10/group); comparisons were made between the high baseline men (HM) and women (HW), and low baseline men (LM) and women (LW). By design, HM and HW, vs. LM and LW, had greater baseline MSNA burst frequency (37±5 and 38±3 vs. 9±4 and 15±5 bursts/min) and burst incidence (59±14 and 60±8 vs. 16±10 and 23±7 bursts/100hbs; both P<0.001). However, baseline BP and HR were not different between the groups (all P>0.05). During the CPT, there were no differences in the increase in BP and HR (all P>0.05). Conversely, ΔMSNA burst frequency was lower in HW vs. LW (8±9 vs. 22±12 bursts/min; P=0.012) yet was similar in HM vs. LM (17±12 vs. 19±10 bursts/min, P=0.994). Further, ΔMSNA burst incidence was lower in HW vs. LW (9±13 vs. 28±16 bursts/100hbs; P=0.020), with no differences between HM vs. LM (21±17 vs. 31±17 bursts/100hbs; P=0.455). Our findings suggest that heightened baseline activity in older women attenuates the typical CPT-mediated increase in MSNA without changing cardiovascular reactivity. While the underlying mechanisms remain unknown, altered sympathetic recruitment or neurovascular transduction may contribute to these disparate responses.

Differential regulation of sympathetic neural burst frequency and amplitude throughout normal pregnancy: a longitudinal study.

Sympathetic activation is a hallmark of pregnancy. However, longitudinal assessments of muscle sympathetic nerve activity (MSNA) in pregnancy are scarce and have primarily focused on burst occurrence (frequency) at rest, despite burst strength (amplitude) representing distinct characteristics of sympathetic outflow. Thus, we assessed MSNA burst amplitude distributions in healthy women to determine the impact of normal pregnancy on neural discharge patterns in response to orthostatic stress. Twenty-six women were studied longitudinally during pre-, early- (4-8 wk of gestation), and late (32-36 wk) pregnancy, as well as postpartum (6-10 wk after delivery). MSNA, blood pressure (BP), and heart rate (HR) were measured in the supine posture and during graded head-up tilt (30° and 60° HUT). Mean and median MSNA burst amplitudes were used to characterize burst amplitude distribution. In late pregnancy, women demonstrated smaller increases in HR (P < 0.001) during 60° HUT and larger increases in systolic BP (P = 0.043) throughout orthostasis, compared with prepregnancy. The increase in MSNA burst frequency during late- relative to prepregnancy (Late: Δ14[10] vs. Pre: Δ21[9] bursts/min; P = 0.001) was smaller during 60° HUT, whereas increases in burst incidence were smaller in late- relative to prepregnancy throughout orthostasis (P = 0.009). Nonetheless, median burst amplitude was smaller throughout orthostasis in late compared with prepregnancy (P = 0.038). Thus, while supine MSNA burst frequency was greater in late pregnancy, increases in burst frequency and strength during orthostasis were attenuated. These smaller, orthostatically induced MSNA increases may reflect natural adaptions of pregnancy serving to prevent sympathetic hyper-reactivity that is common in pathological states.

Exercise Leg Blood Flow Is Preserved in Long-term Breast Cancer Survivors Previously Treated With Anthracycline Chemotherapy.

PURPOSE: The objective of this investigation was to compare the acute hemodynamic responses during single-leg knee extension (SLKE) exercise between female breast cancer (BC) survivors previously treated with anthracycline chemotherapy and age- and sex-matched control (CON) subjects. METHODS: Fourteen BC survivors (age: 61 ± 7 yr; time post-anthracycline therapy: 12 ± 6 yr) and nine CON subjects (age: 59 ± 7 yr) performed SLKE exercise at 25%, 50%, and 75% of peak power output during which heart rate, blood pressure (BP), leg blood flow (Doppler ultrasonography), and vascular conductance (leg blood flow/mean BP) were measured. Quadriceps mass was estimated from thigh volume and skinfold measures. RESULTS: Breast cancer survivors had lower quadriceps mass compared with CON subjects (1803 ± 607 vs 2601 ± 1102 g, P = .04). No difference was found between groups for maximal SLKE power output (28 ± 11 vs 34 ± 17 W, P = .35), heart rate (109 ± 14 vs 103 ± 13 bpm, P = .36), or mean arterial BP (122 ± 18 vs 119 ± 26 mm Hg, P = .33). Rest and submaximal exercise mean arterial BP, leg blood flow (indexed to quadriceps muscle mass), and leg vascular conductance were not significantly different between BC survivors and CON subjects. CONCLUSION: Leg blood flow during submaximal SLKE exercise is preserved in long-term BC survivors previously treated with anthracycline chemotherapy.

The impact of a plant-based diet on indices of cardiovascular health in African Americans: a cross-sectional study.

African-American (AA) individuals are disproportionately affected by cardiovascular diseases. Plant-based diets (PBD) may be cardioprotective in part through their high antioxidant capacity and low inflammatory load. We tested the hypothesis that AA individuals adhering to a 100% PBD would have better vascular health than AA individuals following a typical American diet (TAD). Eighteen AA individuals participated; 9 (24 ± 4 years; 6 females) were following a PBD for 2.4 ± 0.8 years and 9 (21 ± 2 years; 5 females) were following a TAD. Blood lipids and C-reactive protein (CRP) were assessed. Peripheral and central blood pressure (BP) were measured, and vascular function tests included cerebrovascular reactivity to hypercapnia, brachial artery flow-mediated dilation and reactive hyperemia, and local heating-induced cutaneous hyperemia. Total (TC) and low-density lipoprotein (LDL-C) serum cholesterol was lower (TC: 142 ± 30 vs. 174 ± 36 mg/dL; LDL-C: 76 ± 17 vs. 106 ± 33 mg/dL; p < 0.05 and d > 0.80 for both) and serum CRP tended to be lower (0.38 ± 0.18 mg/L vs. 0.96 ± 0.89 mg/L; p = 0.05, d = 0.91) in the PBD cohort. Brachial (b) and central (c) mean arterial BP (MAP) were lower in the PBD cohort (bMAP: 86 ± 5 vs. 91 ± 7 mm Hg; cMAP: 81 ± 5 vs. 87 ± 7 mm Hg; p < 0.05 and d > 0.80 for both). All indices of vascular function were similar between groups (p > 0.05 for all). A PBD was associated with more optimal blood lipid concentrations and decreased peripheral and central BP in AA individuals, but this association was not present in the various indices of vascular function. Registered at ClinicalTrials.gov: NCT05344287.

Young, non-Hispanic Black men and women exhibit divergent peripheral and cerebral vascular reactivity.

NEW FINDINGS: What is the central question of the study? Do peripheral and cerebral vascular function differ between young non-Hispanic Black men and women? What is the main finding and its importance? The non-Hispanic Black women in this study presented greater peripheral conduit artery and cerebrovascular reactivity, yet similar peripheral microvascular function relative to the non-Hispanic Black men. These preliminary findings suggest that young Black women and men possess divergent vascular function, possibly contributing to the unique non-Hispanic Black sex differences in cardiovascular and cerebrovascular diseases. ABSTRACT: In the USA, cardiovascular and cerebrovascular diseases remain more prominent in the non-Hispanic Black (BL) population relative to other racial/ethnic groups. Typically, sex differences emerge in the manifestation of these diseases, though these differences may not fully materialize in the BL population. While numerous mechanisms are implicated, differences in vascular function likely contribute. Research has demonstrated blunted vasodilatation in several vascular regions in BL versus non-Hispanic White individuals, though much of this work did not assess sex differences. Therefore, this study aimed to ascertain if indices of vascular function are different between young BL women (BW) and men (BM). Eleven BW and 15 BM (22 (4) vs. 23 (3) years) participated in this study. Each participant underwent testing for brachial artery flow-mediated dilatation (FMD), post-occlusive reactive hyperaemia and cerebral vasomotor reactivity during rebreathing-induced hypercapnia. BW exhibited greater adjusted FMD than BM (P < 0.05 for all), but similar or lower reactive hyperaemia when assessed as blood velocity (P > 0.39 for all) or blood flow reactivity (P < 0.05 for all), respectively. Across a range of hypercapnia, BW had greater middle cerebral artery blood velocity and cerebrovascular conductance index than BM (P < 0.001 for both). These preliminary data suggest that young BW have greater vascular function relative to young BM, though this was inconsistent across different indices. These findings provide insight into the divergent epidemiological findings between BM and BW. Further research is needed to elucidate possible mechanisms and relate these physiological responses to epidemiological observations.

Global Research Expedition on Altitude-related Chronic Health 2018 Iron Infusion at High Altitude Reduces Hypoxic Pulmonary Vasoconstriction Equally in Both Lowlanders and Healthy Andean Highlanders.

BACKGROUND: Increasing iron bioavailability attenuates hypoxic pulmonary vasoconstriction in both lowlanders and Sherpas at high altitude. In contrast, the pulmonary vasculature of Andean individuals with chronic mountain sickness (CMS) is resistant to iron administration. Although pulmonary vascular remodeling and hypertension are characteristic features of CMS, the effect of iron administration in healthy Andean individuals, to our knowledge, has not been investigated. If the interplay between iron status and pulmonary vascular tone in healthy Andean individuals remains intact, this could provide valuable clinical insight into the role of iron regulation at high altitude. RESEARCH QUESTION: Is the pulmonary vasculature in healthy Andean individuals responsive to iron infusion? STUDY DESIGN AND METHODS: In a double-blinded, block-randomized design, 24 healthy high-altitude Andean individuals and 22 partially acclimatized lowlanders at 4,300 m (Cerro de Pasco, Peru) received an IV infusion of either 200 mg of iron (III)-hydroxide sucrose or saline. Markers of iron status were collected at baseline and 4 h after infusion. Echocardiography was performed in participants during room air breathing (partial pressure of inspired oxygen [Pio2] of approximately 96 mm Hg) and during exaggerated hypoxia (Pio2 of approximately 73 mm Hg) at baseline and at 2 and 4 h after the infusion. RESULTS: Iron infusion reduced pulmonary artery systolic pressure (PASP) by approximately 2.5 mm Hg in room air (main effect, P < .001) and by approximately 7 mm Hg during exaggerated hypoxia (main effect, P < .001) in both lowlanders and healthy Andean highlanders. There was no change in PASP after the infusion of saline. Iron metrics were comparable between groups, except for serum ferritin, which was 1.8-fold higher at baseline in the Andean individuals than in the lowlanders (95% CI, 74-121 ng/mL vs 37-70 ng/mL, respectively; P = .003). INTERPRETATION: The pulmonary vasculature of healthy Andean individuals and lowlanders remains sensitive to iron infusion, and this response seems to differ from the pathologic characteristics of CMS.

GLOBAL REACH 2018: intra-arterial vitamin C improves endothelial-dependent vasodilatory function in humans at high altitude.

High altitude-induced hypoxaemia is often associated with peripheral vascular dysfunction. However, the basic mechanism(s) underlying high-altitude vascular impairments remains unclear. This study tested the hypothesis that oxidative stress contributes to the impairments in endothelial function during early acclimatization to high altitude. Ten young healthy lowlanders were tested at sea level (344 m) and following 4-6 days at high altitude (4300 m). Vascular endothelial function was determined using the isolated perfused forearm technique with forearm blood flow (FBF) measured by strain-gauge venous occlusion plethysmography. FBF was quantified in response to acetylcholine (ACh), sodium nitroprusside (SNP) and a co-infusion of ACh with the antioxidant vitamin C (ACh+VitC). The total FBF response to ACh (area under the curve) was ∼30% lower at high altitude than at sea level (P = 0.048). There was no difference in the response to SNP at high altitude (P = 0.860). At sea level, the co-infusion of ACh+VitC had no influence on the FBF dose response (P = 0.268); however, at high altitude ACh+VitC resulted in an average increase in the FBF dose response by ∼20% (P = 0.019). At high altitude, the decreased FBF response to ACh, and the increase in FBF in response to ACh+VitC, were associated with the magnitude of arterial hypoxaemia (R2 = 0.60, P = 0.008 and R2 = 0.63, P = 0.006, respectively). Collectively, these data support the hypothesis that impairments in vascular endothelial function at high altitude are in part attributable to oxidative stress, a consequence of the magnitude of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourns, with important implications for understanding the aetiology of high altitude-related vascular dysfunction. KEY POINTS: Vascular dysfunction has been demonstrated in lowlanders at high altitude (>4000 m). However, the extent of impairment and the delineation of contributing mechanisms have remained unclear. Using the gold-standard isolated perfused forearm model, we determined the extent of vasodilatory dysfunction and oxidative stress as a contributing mechanism in healthy lowlanders before and 4-6 days after rapid ascent to 4300 m. The total forearm blood flow response to acetylcholine at high altitude was decreased by ∼30%. Co-infusion of acetylcholine with the antioxidant vitamin C partially restored the total forearm blood flow by ∼20%. The magnitude of forearm blood flow reduction, as well as the impact of oxidative stress, was positively associated with the individual severity of hypoxaemia. These data extend our basic understanding of vascular (mal)adaptation to high-altitude sojourns, with important implications for understanding the aetiology of high altitude-related changes in endothelial-mediated vasodilatory function.

Contributions of endothelin-1 and l-arginine to blunted cutaneous microvascular function in young, black women.

Non-Hispanic black (BL) individuals have the greatest prevalence of cardiovascular disease (CVD), relative to other racial/ethnic groups (e.g., non-Hispanic white population; WH), which may be secondary to blunted vascular function. Although women typically present with reduced CVD relative to men of the same racial/ethnic group, the prevalence is similar between BL women and men though the mechanisms differ. This study hypothesized that reduced microvascular function in young, BL women is associated with endothelin-1 (ET-1) overactivity or insufficient l-arginine bioavailability. Nine BL and nine WH women participated (age: 20 ± 2 vs. 22 ± 2 yr). Cutaneous microvascular function was assessed during 39°C local heating, whereas lactated Ringer's (control), BQ-123 (ET-1 receptor type A antagonist), BQ-788 (ET-1 receptor type B antagonist), or l-arginine were infused via intradermal microdialysis to modify cutaneous vascular conductance (CVC). Subsequent infusion of Nω-nitro-l-arginine methyl ester allowed for quantification of the nitric oxide (NO) contribution to vasodilation, whereas combined sodium nitroprusside and 43°C heating allowed for normalization to maximal CVC (%CVCmax). BL women had blunted %CVCmax and NO contribution to dilation during the 39°C plateau (P < 0.027 for both). BQ-123 improved this response through augmented NO-mediated dilation (P < 0.048 for both). BQ-788 and l-arginine did not alter the CVC responses (P > 0.835 for both) or the NO contribution (P > 0.371 for both). Cutaneous microvascular function is reduced in BL women, and ET-1 receptor type A may contribute to this reduced function. Further research is needed to better characterize these mechanisms in young, BL women.NEW & NOTEWORTHY Cardiovascular disease remains a burden in the United States non-Hispanic black (BL) population, although its manifestation through blunted vasodilation in this population is different between men and women. Accordingly, this study determined that reduced microvascular function in young, BL women may be partially controlled by endothelin-1 (ET-1) type A receptors, although neither type B receptors nor insufficient l-arginine bioavailability seems to contribute to this response. Accordingly, further research is needed to better characterize these ET-1 related mechanisms and illuminate other pathways that may contribute to this disparate vascular function in young, BL women.

Cerebrovascular reactivity is blunted in young adults with major depressive disorder: The influence of current depressive symptomology.

BACKGROUND: In middle-aged adults with depression, cerebral vasodilatory reactivity is blunted; however, this has not been examined in treatment-naïve young adults with major depressive disorder (MDD). We tested the hypothesis that cerebrovascular reactivity would be blunted in young adults (18-30 yrs) with MDD compared to healthy non-depressed adults (HA) and would be attenuated to a greater extent in adults with symptomatic MDD (sMDD) compared to adults with MDD in remission (euthymic MDD; eMDD). METHODS: Sixteen adults with MDD [21±3yrs; n = 8 sMDD (6 women); n = 8 eMDD (5 women)] and 14 HA (22±3yrs; 9 women) participated. End-tidal carbon dioxide concentration (PETCO2; capnograph), beat-to-beat mean arterial pressure (MAP; finger photoplethysmography), middle cerebral artery blood velocity (MCAv; transcranial Doppler ultrasound), and internal carotid artery (ICA) diameter and blood velocity (Doppler ultrasound) were continuously measured during baseline and rebreathing-induced hypercapnia. Cerebrovascular reactivity was calculated as the relative increase in vascular conductance during hypercapnia. RESULTS: In adults with MDD, cerebrovascular reactivity in the MCA (∆39±9 HA vs. ∆31±13% MDD, p = 0.04), but not the ICA (∆36±24 HA vs. ∆34±18% MDD, p = 0.84), was blunted compared to HA. In the MCA, cerebrovascular reactivity was reduced in adults with sMDD compared to adults with eMDD (∆36±11 eMDD vs. ∆25±13% sMDD, p = 0.02). LIMITATIONS: The cross-sectional nature approach limits conclusions regarding the temporal nature of this link. CONCLUSION: These data indicate that MCA cerebrovascular reactivity is blunted in young adults with MDD and further modulated by current depressive symptomology, suggesting that the management of depressive symptomology may secondarily improve cerebrovascular health.

Impact of cutaneous blood flow on NIR-DCS measures of skeletal muscle blood flow index.

Near-infrared diffuse correlation spectroscopy (NIR-DCS) is an optical technique for estimating relative changes in skeletal muscle perfusion during exercise but may be affected by changes in cutaneous blood flow, as photons emitted by the laser must first pass through the skin. Accordingly, the purpose of this investigation was to examine how increased cutaneous blood flow affects NIR-DCS blood flow index (BFI) at rest and during exercise using a passive whole body heating protocol that increases cutaneous, but not skeletal muscle, perfusion in the uncovered limb. BFI and cutaneous perfusion (laser-Doppler flowmetry) were assessed in 15 healthy young subjects before (e.g., rest) and during 5 min of moderate-intensity handgrip exercise in normothermic conditions and after cutaneous blood flow was elevated via whole body heating. Hyperthermia significantly increased both cutaneous perfusion (∼7.3-fold; P ≤ 0.001) and NIR-DCS BFI (∼4.5-fold; P ≤ 0.001). Although relative BFI (i.e., fold-change above baseline) exhibited a typical exponential increase in muscle perfusion during normothermic exercise (2.81 ± 0.95), there was almost no change in BFI during hyperthermic exercise (1.43 ± 0.44). A subset of eight subjects were subsequently treated with intradermal injection of botulinum toxin-A (Botox) to block heating-induced elevations in cutaneous blood flow, which 1) nearly abolished the hyperthermia-induced increase in BFI and 2) restored BFI kinetics during hyperthermic exercise to values that were not different from normothermic exercise (P = 0.091). Collectively, our results demonstrate that cutaneous blood flow can have a substantial, detrimental impact on NIR-DCS estimates of skeletal muscle perfusion and highlight the need for technical and/or pharmacological advancements to overcome this issue moving forward.NEW & NOTEWORTHY We used passive whole body heat stress, in combination with local intradermal botulinum toxin type A treatment, to experimentally manipulate cutaneous blood flow and investigate its impact on NIR-DCS measures of skeletal muscle BFI at rest and during exercise. Collectively, the results show that cutaneous blood flow, which was augmented in response to passive whole body heat stress, markedly affects NIR-DCS-derived BFI, such that the BFI signal becomes dominated by changes in cutaneous red blood cell flux.

Global Reach 2018: Nitric oxide-mediated cutaneous vasodilation is reduced in chronic, but not acute, hypoxia independently of enzymatic superoxide formation.

We tested the hypotheses that 1) cutaneous microvascular function is impaired by acute normobaric and chronic hypobaric hypoxia and 2) that the superoxide free radical (via NADPH oxidase or xanthine oxidase) contributes to this impairment via nitric oxide (NO) scavenging. Local heating-induced cutaneous hyperemia (39 °C) was measured in the forearm of 11 male lowlanders at sea level (SL) and following 14-18 days at high altitude (HA; 4340 m in Cerro de Pasco, Peru), and compared to 11 highlanders residing permanently at this elevation. Cutaneous vascular conductance (CVC; laser-Doppler flux/mean arterial pressure) was not different during 39 °C [control site: 73 (19) vs. 71 (18)%max; P = 0.68] between normoxia and acute normobaric hypoxia (FIO2 = 0.125; equivalent to HA), respectively. At HA, CVC was reduced during 39 °C in lowlanders compared to SL [control site: 54 (14) vs. 73 (19)%max; P < 0.01] and was lower in Andean highlanders compared to lowlanders at HA [control site: 50 (24) vs. 54 (14)%max; P = 0.02]. The NO contribution to vasodilation during 39 °C (i.e., effect of NO synthase inhibition) was reduced in lowlanders at HA compared to SL [control site: 41 (11) vs 49 (10)%max; P = 0.04] and in Andean highlanders compared to lowlanders at HA [control site: 32 (21) vs. 41 (11)%max; P = 0.01]. Intradermal administration (cutaneous microdialysis) of the superoxide mimetic Tempol, inhibition of xanthine oxidase (via allopurinol), or NADPH oxidase (via apocynin) had no influence on cutaneous endothelium-dependent dilation during any of the conditions (all main effects of drug P > 0.05). These results suggest that time at HA impairs NO-mediated cutaneous vasodilation independent of enzymatic superoxide formation.

Blunted hyperemic response to mental stress in young, non-Hispanic black men is not impacted by acute dietary nitrate supplementation.

Non-Hispanic black individuals suffer from an elevated prevalence of hypertension and cardiovascular disease (CVD) relative to other populations. This elevated disease risk is, in large part, related to impaired vascular function, secondary to reduced nitric oxide (NO) bioavailability. Emerging evidence suggests that dietary nitrate supplementation improves several cardiovascular parameters, including vascular function, in part by increased NO bioavailability. However, whether these findings extend to a population of black individuals is unknown. This study tested the hypothesis that forearm blood flow responses in young, non-Hispanic, black (BL) men during a mental stress challenge would be blunted relative to young, non-Hispanic, white (WH) men. We further hypothesized that acute dietary nitrate supplementation would improve this response in BL men. This study comprised two parts (phase 1 and phase 2). Phase 1 investigated the difference in blood flow responses between young, BL, and WH men. In contrast, phase 2 investigated the effect of acute nitrate supplementation on the responses in a subset of the BL men from phase 1. Eleven (nine for phase 2) BL and eight WH men (23 ± 3 vs. 24 ± 4 yr, respectively) participated in this double-blind, placebo-controlled, randomized, crossover study. During each visit, hemodynamic responses during 3 min of mental stress were assessed in the brachial artery using duplex Doppler ultrasound. Phase 1 was completed in one visit, whereas phase 2 was completed over two visits separated by ∼1 wk. During phase 2, data were collected before and 2-h postconsumption of a beverage either high in nitrate content or nitrate depleted. In phase 1, peak forearm blood flow (FBF; P < 0.001), total FBF (P < 0.01), and forearm vascular conductance (FVC; P < 0.001) were blunted in the BL. During phase 2, prebeverage responses were similar to phase 1 and were unaffected following beverage consumption (P > 0.05 vs. prebeverage for all variables). These data indicate that young, BL men have blunted microvascular vasodilatory responses to acute mental stress, which may not be altered following acute nitrate supplementation.NEW & NOTEWORTHY This study tested the hypothesis that non-Hispanic black (BL) men have a blunted forearm hyperemic response to mental stress, which would be augmented following acute nitrate supplementation. The increase in forearm blood flow during mental stress was attenuated in BL men and was not impacted by nitrate supplementation. This supports findings of altered vascular function in this population. This is especially important as BL experience a higher prevalence of stress, which contributes to CVD risk.

Differences in joint power distribution in high and low lactate threshold cyclists.

PURPOSE: The biomechanical differences between cyclists with a high compared with a low blood lactate threshold (HLT; 80% VO2max vs LLT, 70% VO2max) have yet to be completely described. We hypothesize that HLT cyclists reduce the stress placed on the knee extensor muscles by increasing the relative contribution from the hip joint during high-intensity cycling. METHOD: Sixteen well-trained endurance athletes, with equally high VO2max while cycling and running completed submaximal tests during incremental exercise to identify lactate threshold ([Formula: see text]) while running and cycling. Subjects were separated into two groups based on % VO2max at LT during cycling (high; HLT: 80.2 ± 2.1% VO2max; n = 8) and (LLT: 70.3 ± 2.9% VO2max; n = 8; p < 0.01). Absolute and relative joint specific powers were calculated from kinematic and pedal forces using inverse dynamics while cycling at intensities ranging from 60-90% VO2max for between group comparisons. RESULT: There was no difference between HLT and LLT in [Formula: see text] (p > 0.05) while running. While cycling in LLT, knee joint absolute power increased with work rate (p < 0.05); however, in HLT no changes in knee joint absolute power occurred with increased work rate (p > 0.05). The HLT generated significantly greater relative hip power compared with the LLT group at 90% VO2max (p < 0.05). CONCLUSION: These data suggest that HLT cyclists exhibit a greater relative hip contribution to power output during cycling at 90% VO2max. These observations support the theory that lactate production during cycling can be reduced by spreading the work rate between various muscle groups.

Influence of sex on heightened vasoconstrictor mechanisms in the non-Hispanic black population.

Cardiovascular disease (CVD) affects individuals of all races and ethnicities; however, its prevalence is highest in non-Hispanic black individuals (BL) relative to other populations. While previous research has provided valuable insight into elevated CVD risk in the BL population, this work has been almost exclusively conducted in men. This is alarming given that BL women suffer from CVD at an equivalent rate to BL men and each has a greater prevalence when compared to all other ethnicities, regardless of sex. The importance of investigating sex differences in mechanisms of cardiovascular function is highlighted by the National Institute of Health requiring sex to be considered as a biological variable in research studies to better our "understanding of key sex influences on health processes and outcomes." The mechanism(s) responsible for the elevated CVD risk in BL women remains unclear and is likely multifactorial. Limited studies in BL women suggest that, while impaired vasodilator capacity is involved, heightened vasoconstrictor tone and/or responsiveness may also contribute. Within this mini-review, we will discuss potential mechanisms of elevated rates of hypertension and other CVDs in BL individuals with a particular focus on young, otherwise healthy, college-aged women. To stimulate academic thought and future research, we will also discuss potential mechanisms for impaired vascular function in BL women, as well as possible divergent mechanisms between BL men and women based on either preliminary data or plausible speculation extending from findings in the existing literature. Last, we will conclude with potential future research directions aimed at better understanding the elevated risk for hypertension and CVD in BL women.