Central and peripheral haemodynamics at exercise onset: the role of central command.

PURPOSE: The involvement of central command in central hemodynamic regulation during exercise is relatively well-known, although its contribution to peripheral hemodynamics at the onset of low-intensity contractions is debated. This study sought to examine central and peripheral hemodynamics during electrically-evoked muscle contractions (without central command) and voluntary muscle activity (with central command). METHODS: Cyclic quadriceps isometric contractions (1 every second), either electrically-evoked (ES; 200 ms trains composed of 20 square waves) or performed voluntarily (VC), were executed by 10 healthy males (26 ± 3 years). In both trials, matched for force output, peripheral and central hemodynamics were analysed. RESULTS: At exercise onset, both ES and VC exhibited equal peaks of femoral blood flow (1276 ± 849 vs. 1117 ± 632 ml/min, p > 0.05) and vascular conductance (15 ± 11 vs. 13 ± 7 ml/min/mmHg, p > 0.05), respectively. Similar peaks of heart rate (86 ± 16 bpm vs. 85 ± 16 bpm), stroke volume (100 ± 20 vs. 99 ± 27 ml), cardiac output (8.2 ± 2.5 vs. 8.5 ± 2.1 L/min), and mean arterial pressure (113 ± 13 vs. 113 ± 3 mmHg), were recorded (all, p > 0.05). After ~ 50 s, all the variables drifted to lower values. Collectively, the hemodynamics showed equal responses. CONCLUSION: These results suggest a similar pathway for the initial (first 40 s) increase in central and peripheral hemodynamics. The parallel responses may suggest an initial minimal central command involvement during the onset of low-intensity contractions, likely associated with a neural drive activation delay or threshold.

Does sex influence near-infrared spectroscopy-derived indicators of microvascular reactivity and the response to acute dietary capsaicin.

Endothelial dysfunction is associated with cardiovascular disease development, nitric oxide (NO) deficiencies, and may be limb or sex-specific. Prior in vitro work indicated that the transient receptor potential vanilloid channel-1 (TRPV1) is expressed in human arteries and the TRPV1 agonist capsaicin alters vasodilation in an endothelium-dependent manner; however, it is unknown if this translates in vivo or is limb or sex-dependent. Therefore, we sought to determine if there was limb or sex-specificity in the effect of capsaicin on microvascular function using near-infrared spectroscopy (NIRS)-derived tissue oxygen saturation (StO2) reperfusion slope. In a blinded placebo-controlled crossover design, 45 young males (M: n = 25) and females (F: n = 20), the reperfusion slopes of the forearm and quadriceps were assessed, and a urine sample obtained to assay for nitrate/nitrite (NOx) concentrations and antioxidant capacity after acutely ingesting placebo or capsaicin. Under placebo, females had greater reperfusion rates in both the forearm (M: 0.44 ± 0.24 vs. F: 0.98 ± 0.46 %/sec; p = 0.002, d = -1.50) and quadricep (M: 0.86 ± 0.31 vs. F: 1.17 ± 0.43 %/sec; p = 0.010, d = -0.85). Capsaicin decreased microvascular responsiveness in the forearm of females (placebo: 0.98 ± 0.45 vs. capsaicin: 0.84 ± 0.45 %/sec) as compared to males (placebo: 0.45 ± 0.24 vs. capsaicin: 0.38 ± 0.16 %/sec, interaction p < 0.001, η2 = 0.475). There was a sex*treatment interaction for NOx concentrations, where males increased (placebo: 21.13 ± 12.83 vs. capsaicin: 23.82 ± 13.34 µM), while females decreased (placebo: 22.78 ± 14.40 vs. capsaicin: 14.43 ± 10.01 µM; p = 0.037, η2 = 0.042). Using NIRS to assess microvascular function, there is apparent limb and sex-specificity, and, for the first-time, document that acute oral capsaicin alters reperfusion slope in a sexually divergent manner.

Sex differences in estimates of cardiac autonomic function using heart rate variability: effects of dietary capsaicin.

PURPOSE: Heart rate variability (HRV) estimates the autonomic nervous system (ANS) influence on the heart and appears sex-specific. Sensory afferents exhibit sex-specificity; although, it is unknown if Capsaicin, an agonist for transient receptor potential vanilloid channel-1 (TRPV1), alters cardiac ANS activity in a sex-dependent manner, which could be important given the predictive nature of HRV on risk of developing hypertension. Thus, we explored if there was sex-specificity in the effect of capsaicin on estimated cardiac ANS activity. METHODS: HRV was measured in 38 young males (M: n = 25) and females (F: n = 13), in a blinded-crossover design, after acute ingestion of placebo or capsaicin. Resting HR, RR-interval, root-mean-square of successive differences (RMSSD), natural log-transformed RMSSD (LnRMSSD), standard deviation of n-n intervals (SDNN), number of pairs of successive n-n intervals differing by > 50 ms (NN50), and percent NN50 (PNN50) were obtained using standard techniques. RESULTS: Significant sex differences were observed in mean HR (M: 59 ± 9.3 vs. F: 65 ± 12 beats/min, p = 0.036, η2 = 0.098), minimum HR (M: 47 ± 8.3 vs. F: 56 ± 12 beats/min, p = 0.014, η2 = 0.124), and NN50 (M: 177 ± 143 vs. F: 29 ± 17, p < 0.001, η2 = 0.249). There was a significant interaction of sex*treatment (p = 0.02, η2 = 0.027) for RMSSD, where males increased (78 ± 55 vs. 91 ± 64 ms), and females decreased (105 ± 83 vs. 76 ± 43 ms), placebo vs. capsaicin. CONCLUSION: This controlled study recapitulates sex differences in HR and HRV, but revealed a sexual dimorphism in the parasympathetic response to capsaicin, perhaps due to differing TRPV1-afferent sensitivity, highlighting a potential mechanism for differential regulation of hemodynamics, and CVD risk, and should be considered in future studies.

Subjective sleep score is associated with central and peripheral blood pressure values in children aged 7-12 years.

Shortened and poor-quality sleep have emerged as non-traditional risk factors for the development of hypertension in adults, and it is likely these relations extend to paediatric populations when evaluating sleep subjectively. Therefore, we aimed to evaluate subjective sleep metrics and their associations with central and peripheral blood pressure (BP) values in children. We hypothesized that poor-quality sleep and short sleep duration would be associated with elevated pressures in healthy children. Subjective sleep habits and sleep duration were evaluated using the Children's Sleep Habits Questionnaire (CSHQ) in 29 children aged 7-12 years (13 male/16 female). A total sleep score was generated by summing subscale scores: a higher score indicates poorer sleep habits. Peripheral BP was measured, and central pressures were estimated using pulse wave analysis. Pearson's r correlations were used to assess relations between total sleep score, sleep duration, and sleep score subscales with BP values. Sleep score was positively associated with central and peripheral systolic pressure (r = 0.43, p = 0.02 and r = 0.41, p = 0.03, respectively), diastolic pressure (r = 0.42, p = 0.02 and r = 0.36, p = 0.05, respectively) and mean arterial pressure (r = 0.40, p = 0.03 and r = 0.36, p = 0.03, respectively). Sleep duration was negatively associated with central and peripheral diastolic pressure (r = -0.40, p = 0.03 and r = -0.41, p = 0.03, respectively). Regarding the CSHQ subscales, daytime sleepiness and parasomnias were consistently positively associated with BP values. These findings support sleep as a primordial prevention target for hypertension and the maintenance of cardiovascular health during childhood. Consideration of a variety of sleep habits using tools such as the CSHQ may provide important insights into early-life cardiovascular risk.

Intermittent fasting two days versus one day per week, matched for total energy intake and expenditure, increases weight loss in overweight/obese men and women.

BACKGROUND: Intermittent fasting (IF), consisting of either a one-day (IF1) or two consecutive days (IF2) per week, is commonly used for optimal body weight loss. Our laboratory has previously shown an IF1 diet combined with 6d/week of protein pacing (P; 4-5 meals/day evenly spaced, ~ 30% protein/day) significantly enhances weight loss, body composition, and cardiometabolic health in obese men and women. Whether an IF1-P or IF2-P, matched for weekly energy intake (EI) and expenditure (EE), is superior for weight loss, body composition, and cardiometabolic health is unknown. METHODS: This randomized control study directly compared an IF1-P (n = 10) versus an IF2-P (n = 10) diet on weight loss and body composition, cardiovascular (blood pressure and lipids), hormone, and hunger responses in 20 overweight men and women during a 4-week weight loss period. Participants received weekly dietary counseling and monitoring of compliance from a registered dietitian. All outcome variables were assessed pre (week 0) and post (week 5). RESULTS: Both groups significantly reduced body weight, waist circumference, percent body fat, fat mass, hunger, blood pressure, lipids, glucose, and increased percent fat-free mass (p < 0.05). However, IF2-P resulted in significantly greater reductions in body weight (-29%) and waist circumference (-38%) compared to IF1-P (p < 0.05), and showed a strong tendency for greater reductions in fat mass, glucose, and hunger levels (p < 0.10) despite similar weekly total EI (IF1-P, 9058 ± 692 vs. IF2-P, 8389 ± 438 kcals/week; p = 0.90), EE (~ 300 kcals/day; p = 0.79), and hormone responses (p > 0.10). CONCLUSIONS: These findings support short-term IF1-P and IF2-P to optimize weight loss and improve body composition, cardiometabolic health, and hunger management, with IF2-P providing enhanced benefits in overweight women and men. TRIAL REGISTRATION: This trial was registered March 03, 2020 at www. CLINICALTRIALS: gov as NCT04327141 .

The Efficacy of Heart Rate Variability in Tracking Travel and Training Stress in Youth Female Rowers: A Preliminary Study.

Egan-Shuttler, JD, Edmonds, R, and Ives, SJ. The efficacy of heart rate variability in tracking travel and training stress in youth female rowers: A preliminary study. J Strength Cond Res 34(11): 3293-3300, 2020-Heart rate variability (HRV) is a reliable indicator of cardiac parasympathetic activity and has been used in athletic populations to measure training adaptations. To date, there is limited research showing whether HRV is practical in youth female athletes and rowers during short periods of overload training. The purpose of this study was to evaluate the practicality of HRV in documenting training responses during a period of overload training in youth female rowers. Time-domain (SD of N-N intervals, SDNN; root mean square of successive differences, RMSSD) and nonlinear (SD1) indices of HRV were recorded during baseline training, daily during the 6-day training camp, and 1 week after the camp in 5 athletes from an elite, high-school, rowing team. Training duration and rate of perceived exertion were recorded to document training load. Training load during the camp was 76% above the athlete's normal workload (2,258 ± 459 vs. 1,280 ± 356 arbitrary units (a.u.)). Using progressive statistics, cardiac vagal activity (RMSSD and SD1) was very likely reduced during each day of the camp when compared with baseline training, although returned to baseline within a week of the training camp. Interestingly, SDNN was reduced throughout the training camp and remained reduced up to a week after the training camp (78% likely; effect size = -0.32). These insights add value to HRV's use in youth sport and provides coaches with an easy, cost-effective means to monitor the physiological response to training, allowing fine-tuning of training, potentially enhancing performance.

α-Adrenergic receptor regulation of skeletal muscle blood flow during exercise in heart failure patients with reduced ejection fraction.

Patients suffering from heart failure with reduced ejection fraction (HFrEF) experience impaired limb blood flow during exercise, which may be due to a disease-related increase in α-adrenergic receptor vasoconstriction. Thus, in eight patients with HFrEF (63 ± 4 yr) and eight well-matched controls (63 ± 2 yr), we examined changes in leg blood flow (Doppler ultrasound) during intra-arterial infusion of phenylephrine (PE; an α1-adrenergic receptor agonist) and phentolamine (Phen; a nonspecific α-adrenergic receptor antagonist) at rest and during dynamic single-leg knee-extensor exercise (0, 5, and 10 W). At rest, the PE-induced reduction in blood flow was significantly attenuated in patients with HFrEF (-15 ± 7%) compared with controls (-36 ± 5%). During exercise, the controls exhibited a blunted reduction in blood flow induced by PE (-12 ± 4, -10 ± 4, and -9 ± 2% at 0, 5, and 10 W, respectively) compared with rest, while the PE-induced change in blood flow was unchanged compared with rest in the HFrEF group (-8 ± 5, -10 ± 3, and -14 ± 3%, respectively). Phen administration increased leg blood flow to a greater extent in the HFrEF group at rest (+178 ± 34% vs. +114 ± 28%, HFrEF vs. control) and during exercise (36 ± 6, 37 ± 7, and 39 ± 6% vs. 13 ± 3, 14 ± 1, and 8 ± 3% at 0, 5, and 10 W, respectively, in HFrEF vs. control). Together, these findings imply that a HFrEF-related increase in α-adrenergic vasoconstriction restrains exercising skeletal muscle blood flow, potentially contributing to diminished exercise capacity in this population.

TRPV1 channels in human skeletal muscle feed arteries: implications for vascular function.

NEW FINDINGS: What is the central question of this study? We sought to determine whether human skeletal muscle feed arteries (SFMAs) express TRPV1 channels and what role they play in modulating vascular function. What is the main finding and its importance? Human SMFAs do express functional TRPV1 channels that modulate vascular function, specifically opposing α-adrenergic receptor-mediated vasocontraction and potentiating vasorelaxation, in an endothelium-dependent manner, as evidenced by the α1 -receptor-mediated responses. Thus, the vasodilatory role of TRPV1 channels, and their ligand capsaicin, could be a potential therapeutic target for improving vascular function. Additionally, given the 'sympatholytic' effect of TRPV1 activation and known endogenous activators (anandamide, reactive oxygen species, H+ , etc.), TRPV1 channels might contribute to functional sympatholysis during exercise. To examine the role of the transient receptor potential vanilloid type 1 (TRPV1 ) ion channel in the vascular function of human skeletal muscle feed arteries (SMFAs) and whether activation of this heat-sensitive receptor could be involved in modulating vascular function, SMFAs from 16 humans (63 ± 5 years old, range 41-89 years) were studied using wire myography with capsaicin (TRPV1 agonist) and without (control). Specifically, phenylephrine (α1 -adrenergic receptor agonist), dexmedetomidine (α2 -adrenergic receptor agonist), ACh and sodium nitroprusside concentration-response curves were established to assess the role of TRPV1 channels in α-receptor-mediated vasocontraction as well as endothelium-dependent and -independent vasorelaxation, respectively. Compared with control conditions, capsaicin significantly attenuated maximal vasocontraction in response to phenylephrine [control, 52 ± 8% length-tensionmax (LTmax ) and capsaicin, 21 ± 5%LTmax ] and dexmedetomidine (control, 29 ± 12%LTmax and capsaicin, 2 ± 3%LTmax ), while robustly enhancing maximal vasorelaxation with ACh (control, 78 ± 8% vasorelaxation and capsaicin, 108 ± 13% vasorelaxation) and less clearly enhancing the sodium nitroprusside response. Denudation of the endothelium greatly attenuated the maximal ACh-induced vasorelaxation equally in the control and capsaicin conditions (∼17% vasorelaxation) and abolished the attenuating effect of capsaicin on the maximal phenylephrine response (denuded + capsaicin, 61 ± 20%LTmax ). Immunohistochemistry identified a relatively high density of TRPV1 channels in the endothelium compared with the smooth muscle of the SMFAs, but because of the far greater volume of smooth muscle, total TRPV1 protein content was not significantly attenuated by denudation. Thus, SMFAs ubiquitously express functional TRPV1 channels, which alter vascular function, in terms of α1 -receptors, in a predominantly endothelium-dependent manner, conceivably contributing to the functional sympatholysis and unveiling a therapeutic target.

Impact of age on the vasodilatory function of human skeletal muscle feed arteries.

Although advancing age is often associated with attenuated skeletal muscle blood flow and skeletal muscle feed arteries (SMFAs) have been recognized to play a regulatory role in the vasculature, little is known about the impact of age on the vasodilatory capacity of human SMFAs. Therefore, endothelium-dependent and -independent vasodilation were assessed in SMFAs (diameter: 544 ± 63 µm) obtained from 24 (equally represented) young (33 ± 2 yr) and old (71 ± 2 yr) subjects in response to three stimuli: 1) flow-induced shear stress, 2) ACh, and 3) sodium nitropusside (SNP). Both assessments of endothelium-dependent vasodilation, flow (young subjects: 68 ± 1% and old subjects: 32 ± 7%) and ACh (young subjects: 92 ± 3% and old subjects: 73 ± 4%), were significantly blunted (P < 0.05) in SMFAs of old compared with young subjects, with no such age-related differences in endothelium-independent vasodilation (SNP). In response to an increase in flow-induced shear stress, vasodilation kinetics (time constant to reach 63% of the amplitude of the response: 55 ± 1 s in young subjects and 92 ± 7 s in old subjects) and endothelial nitric oxide synthase (eNOS) activation (phospho-eNOS(s1177)/total eNOS: 1.0 ± 0.1 in young subjects and 0.2 ± 0.1 in old subjects) were also significantly attenuated in old compared with young subjects (P < 0.05). Furthermore, the vessel superoxide concentration was greater in old subjects (old subjects: 3.9 ± 1.0 area under curve/mg and young subjects: 1.7 ± 0.1 area under the curve/mg, P < 0.05). These findings reveal that the endothelium-dependent vasodilatory capacity, including vasodilation kinetics but not smooth muscle function, of human SMFAs is blunted with age and may be due to free radicals. Given the potential regulatory role of SMFAs in skeletal muscle blood flow, these findings may explain, at least in part, the often observed attenuated perfusion of skeletal muscle with advancing age that may contribute to exercise intolerance in the elderly.

Ascorbic acid improves brachial artery vasodilation during progressive handgrip exercise in the elderly through a nitric oxide-mediated mechanism.

The proposed mechanistic link between the age-related attenuation in vascular function and free radicals is an attractive hypothesis; however, direct evidence of free radical attenuation and a concomitant improvement in vascular function in the elderly is lacking. Therefore, this study sought to test the hypothesis that ascorbic acid (AA), administered intra-arterially during progressive handgrip exercise, improves brachial artery (BA) vasodilation in a nitric oxide (NO)-dependent manner, by mitigating free radical production. BA vasodilation (Doppler ultrasound) and free radical outflow [electron paramagnetic resonance (EPR) spectroscopy] were measured in seven healthy older adults (69 ± 2 yr) during handgrip exercise at 3, 6, 9, and 12 kg (∼13-52% of maximal voluntary contraction) during the control condition and nitric oxide synthase (NOS) inhibition via N(G)-monomethyl-L-arginine (L-NMMA), AA, and coinfusion of l-NMMA + AA. Baseline BA diameter was not altered by any of the treatments, while L-NMMA and L-NMMA + AA diminished baseline BA blood flow and shear rate. AA improved BA dilation compared with control at 9 kg (control: 6.5 ± 2.2%, AA: 10.9 ± 2.5%, P = 0.01) and 12 kg (control: 9.5 ± 2.7%, AA: 15.9 ± 3.7%, P < 0.01). NOS inhibition blunted BA vasodilation compared with control and when combined with AA eliminated the AA-induced improvement in BA vasodilation. Free radical outflow increased with exercise intensity but, interestingly, was not attenuated by AA. Collectively, these results indicate that AA improves BA vasodilation in the elderly during handgrip exercise through an NO-dependent mechanism; however, this improvement appears not to be the direct consequence of attenuated free radical outflow from the forearm.

Exercise-induced heat stress disrupts the shear-dilatory relationship.

NEW FINDINGS: What is the central question of this study? Although heat stress is known to increase cardiovascular strain, no study, to date, had explored the potential impact of exercise-induced heat stress on vascular function. What is the main finding and its importance? We found that acute exercise tended to reduce flow-mediated dilatation (FMD), owing in part to reduced reactive hyperaemia/shear stimulus; thus, when FMD is normalized to shear no postexercise deficit exists. Exercise-induced heat stress increased reactive hyperaemia, shear rate, coupled with a sustained FMD postexercise, suggests that exercise-induced heat stress increases the amount of shear stimulus to elicit a similar response, indicating reduced vascular responsiveness, or reserve, which might increase cardiovascular susceptibility. Heat stress increases cardiovascular strain and is of particular concern in occupations, such as firefighting, in which individuals are required to perform strenuous work while wearing personal protective equipment. Sudden cardiac events are associated with strenuous activity and are the leading cause of duty-related death among firefighters, accounting for ∼50% of duty-related fatalities per year. Understanding the acute effects of exercise-induced heat stress (EIHS) on vascular endothelial function may provide insight into the mechanisms precipitating acute coronary events in firefighters. The purpose of this study, therefore, was to determine the effects of EIHS on vascular endothelial function. Using a balanced crossover design, 12 healthy men performed 100 min of moderate-intensity, intermittent exercise with and without EIHS (personal protective equipment or cooling vest, respectively). Measurements of flow-mediated dilatation (FMD), reactive hyperaemia and shear rate area under the curve (SRAUC ) were performed pre- and postexercise. During EIHS, core temperature was significantly higher (38 ± 0.1 versus 37 ± 0.1°C). Postexercise FMD tended to be suppressed in both conditions, but was not different from pre-exercise. Reactive hyperaemia was reduced after no-EIHS but increased after EIHS. Thus, normalizing FMD to the shear stimulus (FMD/SRAUC ) revealed a significant reduction in FMD after EIHS only (pre-exercise 0.15 ± 0.04 and 0.13 ± 0.02 s-1 versus postexercise, 0.13 ± 0.02 and 0.06 ± 0.02 s-1 , no-EIHS and EIHS, respectively). We conclude that moderate heat stress superimposed on moderate-intensity exercise resulted in reduced vascular endothelial function. This heat stress-induced alteration in the shear-dilatory relationship may relate to the increased risk of acute coronary events associated with activities that combine physical exertion and heat stress (i.e. firefighting).

The role of nitric oxide in passive leg movement-induced vasodilatation with age: insight from alterations in femoral perfusion pressure.

The passive leg movement (PLM) model is a novel approach to assess vascular function. Increasing femoral perfusion pressure (FPP) by moving from the supine to the upright-seated posture augments the vasodilatory response to PLM in the young, with no effect in the old, but whether this augmented vasodilatation is nitric oxide (NO) dependent is unknown. Using an intra-arterial infusion of N(G) -monomethyl-L -arginine (L -NMMA) to inhibit nitric oxide synthase (NOS), the posture-induced increases in the PLM responses in the young were nearly ablated, with no effect of NOS inhibition in the old. Therefore, PLM in combination with alterations in posture can be used to determine changes in NO-mediated vasodilatation with age, and thus, may be a clinically useful tool for assessing NO bioavailability across the human lifespan. We sought to better understand the contribution of nitric oxide (NO) to passive leg movement (PLM)-induced vasodilatation with age, with and without a posture-induced increase in femoral perfusion pressure (FPP). PLM was performed in eight young (24 ± 1 years) and eight old (74 ± 3 years) healthy males, with and without NO synthase inhibition via intra-arterial infusion of N(G) -monomethyl-L -arginine (L -NMMA) into the common femoral artery in both the supine and upright-seated posture. Central and peripheral haemodynamic responses were determined second-by-second with finger photoplethysmography and Doppler ultrasound, respectively. PLM-induced increases in heart rate, stroke volume, cardiac output and reductions in mean arterial pressure were similar between age groups and conditions. In the young, L -NMMA attenuated the peak change in leg vascular conductance (ΔLVCpeak ) in both the supine (control: 7.4 ± 0.9; L -NMMA: 5.2 ± 1.1 ml min(-1) mmHg(-1) , P < 0.05) and upright-seated (control: 12.3 ± 2.0; L -NMMA: 6.4 ± 1.0 ml min(-1) mmHg(-1) , P < 0.05) posture, with no significant change in the old (supine control: 4.2 ± 1.3; supine L -NMMA: 3.4 ± 0.8; upright-seated control: 4.5 ± 0.8; upright-seated L -NMMA: 3.4 ± 0.8 ml min(-1) mmHg(-1) , P > 0.05). Increased FPP augmented the ΔLVCpeak in the young control condition only (P < 0.05). In the upright-seated posture, NOS inhibition attenuated the FPP-induced augmentation of rapid vasodilatation in the young (control: 1.25 ± 0.23; L -NMMA: 0.74 ± 0.11 ml min(-1) mmHg(-1) s(-1) ; P < 0.05), but not the old (control: 0.37 ± 0.07; L -NMMA: 0.25 ± 0.07 ml ml min(-1) mmHg(-1) s(-1) ; P > 0.05). These data reveal that greater FPP increases the role of NO in PLM-induced vasodilatation in the young, but not the old, due to reduced NO bioavailability with age. Therefore, PLM involving alterations in posture may be useful to determine changes in NO bioavailability with age.

Passive leg movement-induced vasodilation in women: the impact of age.

Passive leg movement (PLM), an assessment of predominantly nitric oxide-dependent vasodilation, is decreased with age and cannot be augmented by posture-induced increases in femoral perfusion pressure in older men. However, this novel method of assessing vascular function has yet to be used to evaluate alterations in nitric oxide-dependent vasodilation with age in females. PLM was performed in 10 young (20 ± 1 yr) and 10 old (73 ± 2 yr) women in both the supine and upright-seated postures, whereas central and peripheral hemodynamic measurements were acquired second by second using noninvasive techniques (finger photoplethysmography and Doppler ultrasound, respectively). The heart rate response to PLM was attenuated in the old compared with the young in both the supine (young, 10 ± 1; and old, 5 ± 1 beats/min; P < 0.05) and upright-seated posture (young, 10 ± 2; and old, 5 ± 1 beats/min; P < 0.05), leading to a blunted cardiac output response in the old in the upright-seated posture (young, 1.0 ± 0.2; and old, 0.3 ± 0.1 l/min; P < 0.05). The PLM-induced peak change in leg vascular conductance was lower in the old compared with the young in both postures (young supine, 5.7 ± 0.5; old supine, 2.6 ± 0.3; young upright, 9.2 ± 0.7; and old upright, 2.2 ± 0.4 ml·min(-1)·mmHg(-1); P < 0.05) and was significantly augmented by the upright-seated posture in the young only, revealing a vasodilatory reserve capacity in the young (3.5 ± 0.6 ml·min(-1)·mmHg(-1), P < 0.05) that was absent in the old (-0.5 ± 0.3 ml·min(-1)·mmHg(-1), P = 0.18). These data support previous literature demonstrating attenuated PLM-induced vasodilation with age and extend these findings to include the female population, thus bolstering the utility of PLM as a novel assessment of vascular function across the life span in humans.

Passive leg movement and nitric oxide-mediated vascular function: the impact of age.

In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106; L-NMMA: 431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98; L-NMMA: 251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: -31 ± 18 ml) than the young (LBF: -129 ± 21 ml; P < 0.01). These findings suggest that the age-associated reduction in PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.

Oral antioxidants improve leg blood flow during exercise in patients with chronic obstructive pulmonary disease.

The consequence of elevated oxidative stress on exercising skeletal muscle blood flow as well as the transport and utilization of O2 in patients with chronic obstructive pulmonary disease (COPD) is not well understood. The present study examined the impact of an oral antioxidant cocktail (AOC) on leg blood flow (LBF) and O2 consumption during dynamic exercise in 16 patients with COPD and 16 healthy subjects. Subjects performed submaximal (3, 6, and 9 W) single-leg knee extensor exercise while LBF (Doppler ultrasound), mean arterial blood pressure, leg vascular conductance, arterial O2 saturation, leg arterial-venous O2 difference, and leg O2 consumption (direct Fick) were evaluated under control conditions and after AOC administration. AOC administration increased LBF (3 W: 1,604 ± 100 vs. 1,798 ± 128 ml/min, 6 W: 1,832 ± 109 vs. 1,992 ± 120 ml/min, and 9W: 2,035 ± 114 vs. 2,187 ± 136 ml/min, P < 0.05, control vs. AOC, respectively), leg vascular conductance, and leg O2 consumption (3 W: 173 ± 12 vs. 210 ± 15 ml O2/min, 6 W: 217 ± 14 vs. 237 ± 15 ml O2/min, and 9 W: 244 ± 16 vs 260 ± 18 ml O2/min, P < 0.05, control vs. AOC, respectively) during exercise in COPD, whereas no effect was observed in healthy subjects. In addition, the AOC afforded a small, but significant, improvement in arterial O2 saturation only in patients with COPD. Thus, these data demonstrate a novel beneficial role of AOC administration on exercising LBF, O2 consumption, and arterial O2 saturation in patients with COPD, implicating oxidative stress as a potential therapeutic target for impaired exercise capacity in this population.

Exploring the vascular smooth muscle receptor landscape in vivo: ultrasound Doppler versus near-infrared spectroscopy assessments.

Ultrasound Doppler and near-infrared spectroscopy (NIRS) are routinely used for noninvasive monitoring of peripheral hemodynamics in both clinical and experimental settings. However, the comparative ability of these methodologies to detect changes in microvascular and whole limb hemodynamics during pharmacological manipulation of vascular smooth muscle receptors located at varied locations within the arterial tree is unknown. Thus, in 10 healthy subjects (25 ± 2 yr), changes in resting leg blood flow (ultrasound Doppler; femoral artery) and muscle oxygenation (oxyhemoglobin + oxymyoglobin; vastus lateralis) were simultaneously evaluated in response to intra-arterial infusions of phenylephrine (PE, 0.025-0.8 µg·kg(-1)·min(-1)), BHT-933 (2.5-40 µg·kg(-1)·min(-1)), and angiotensin II (ANG II, 0.5-8 ng·kg(-1)·min(-1)). All drugs elicited significant dose-dependent reductions in leg blood flow and oxyhemoglobin + oxymyoglobin. Significant relationships were found between ultrasound Doppler and NIRS changes across doses of PE (r(2) = 0.37 ± 0.08), BHT-933 (r(2) = 0.74 ± 0.06), and ANG II (r(2) = 0.68 ± 0.13), with the strongest relationships evident with agonists for receptors located preferentially "downstream" in the leg microcirculation (BHT-933 and ANG II). Analyses of drug potency revealed similar EC50 between ultrasound Doppler and NIRS measurements for PE (0.06 ± 0.02 vs. 0.10 ± 0.01), BHT-933 (5.0 ± 0.9 vs. 4.5 ± 1.3), and ANG II (1.4 ± 0.8 vs. 1.3 ± 0.3). These data provide evidence that both ultrasound Doppler and NIRS track pharmacologically induced changes in peripheral hemodynamics and are equally capable of determining drug potency. However, considerable disparity was observed between agonist infusions targeting different levels of the arterial tree, suggesting that receptor landscape is an important consideration for proper interpretation of hemodynamic monitoring with these methodologies.

α1- and α2-adrenergic responsiveness in human skeletal muscle feed arteries: the role of TRPV ion channels in heat-induced sympatholysis.

The purpose of this study was to determine if heat inhibits α2-adrenergic vasocontraction, similarly to α1-adrenergic contraction, in isolated human skeletal muscle feed arteries (SMFA) and elucidate the role of the temperature-sensitive vanilloid-type transient receptor potential (TRPV) ion channels in this response. Isolated SMFA from 37 subjects were studied using wire myography. α1 [Phenylephrine (PE)]- and α2 [dexmedetomidine (DEX)]-contractions were induced at 37 and 39°C with and without TRPV family and TRPV4-specific inhibition [ruthenium red (RR) and RN-1734, respectively]. Endothelial function [acetylcholine (ACh)] and smooth muscle function [sodium nitroprusside (SNP) and potassium chloride (KCl)] were also assessed under these conditions. Heat and TRPV inhibition was further examined in endothelium-denuded arteries. Contraction data are reported as a percentage of maximal contraction elicited by 100 mM KCl (LTmax). DEX elicited a small and variable contractile response, one-fifth the magnitude of PE, which was not as clearly attenuated when heated from 37 to 39°C (12 ± 4 to 6 ± 2% LTmax; P = 0.18) as were PE-induced contractions (59 ± 5 to 24 ± 4% LTmax; P < 0.05). Both forms of TRPV inhibition restored PE-induced contraction at 39°C (P < 0.05) implicating these channels, particularly the TRPV4 channels, in the heat-induced attenuation of α1-adrenergic vasocontraction. TRPV inhibition significantly blunted ACh relaxation while denudation prevented heat-induced sympatholysis without having an additive effect when combined with TRPV inhibition. In conclusion, physiological increases in temperature elicit a sympatholysis-like inhibition of α1-adrenergic vasocontraction in human SMFA that appears to be mediated by endothelial TRPV4 ion channels.

Cardiac, skeletal, and smooth muscle mitochondrial respiration: are all mitochondria created equal?

Unlike cardiac and skeletal muscle, little is known about vascular smooth muscle mitochondrial respiration. Therefore, the present study examined mitochondrial respiratory rates in smooth muscle of healthy human feed arteries and compared with that of healthy cardiac and skeletal muscles. Cardiac, skeletal, and smooth muscles were harvested from a total of 22 subjects (53 ± 6 yr), and mitochondrial respiration was assessed in permeabilized fibers. Complex I + II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac to skeletal to smooth muscles (54 ± 1, 39 ± 4, and 15 ± 1 pmol·s(-1)·mg(-1), P < 0.05, respectively). Citrate synthase (CS) activity, an index of mitochondrial density, also fell progressively from cardiac to skeletal to smooth muscles (222 ± 13, 115 ± 2, and 48 ± 2 µmol·g(-1)·min(-1), P < 0.05, respectively). Thus, when respiration rates were normalized by CS (respiration per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, complex I state 2 normalized for CS activity, an index of nonphosphorylating respiration per mitochondrial content, increased progressively from cardiac to skeletal to smooth muscles, such that the respiratory control ratio, state 3/state 2 respiration, fell progressively from cardiac to skeletal to smooth muscles (5.3 ± 0.7, 3.2 ± 0.4, and 1.6 ± 0.3 pmol·s(-1)·mg(-1), P < 0.05, respectively). Thus, although oxidative phosphorylation capacity per mitochondrial content in cardiac, skeletal, and smooth muscles suggest all mitochondria are created equal, the contrasting respiratory control ratio and nonphosphorylating respiration highlight the existence of intrinsic functional differences between these muscle mitochondria. This likely influences the efficiency of oxidative phosphorylation and could potentially alter ROS production.

Limb, sex, but not acute dietary capsaicin, modulate the near-infrared spectroscopy-vascular occlusion test estimate of muscle metabolism.

The downward slope during the near-infrared spectroscopy (NIRS)-vascular occlusion test (NIRS-VOT) is purported as a simplified estimate of metabolism. Whether or not the NIRS-VOT exhibits sex- or limb-specificity or may be acutely altered remains to be elucidated. Thus, we investigated if there is limb- or sex specificity in tissue desaturation rates (DeO2) during a NIRS-VOT, and if acute dietary capsaicin may alter this estimate of muscle metabolism. Young healthy men (n = 25, 21 ± 4 years) and women (n = 20, 20 ± 1 years) ingested either placebo or capsaicin, in a counterbalanced, single-blind, crossover design after which a simplified NIRS-VOT was conducted to determine the DeO2 (%/s), as an estimate of oxidative muscle metabolism, in both the forearm (flexors) and thigh (vastus lateralis). There was a significant limb effect with the quadriceps having a greater DeO2 than the forearm (-2.31 ± 1.34 vs. -1.78 ± 1.22%/s, p = 0.007, ηp 2 = 0.19). There was a significant effect of sex on DeO2 (p = 0.005, ηp 2 = 0.203) with men exhibiting a lesser DeO2 than women (-1.73 ± 1.03 vs. -2.36 ± 1.32%/s, respectively). This manifested in significant interactions of limb*capsaicin (p = 0.001, ηp 2 = 0.26) as well as limb*capsaicin*sex on DeO2 (p = 0.013, ηp 2 = 0.16) being observed. Capsaicin does not clearly alter O2-dependent muscle metabolism, but there was apparent limb and sex specificity, interacting with capsaicin in this NIRS-derived assessment.

Exploring the Bob Ross effect: A psychophysiological investigation.

Watching news broadcasts is known to elicit psychological stress. Conversely, the iconic painter Bob Ross (BR) has risen to pop culture status and amassed a following, as many find the messages and sounds of BR to be soothing and relaxing. Though, it has yet to be directly tested if such exposure can confer psychological or physiological benefit. The purpose of this study was to compare the effects of watching BR versus streaming news on markers of cardiovascular health and profile of mood states (POMS). It was hypothesized that watching BR would increase POMS scores and heart rate variability (HRV). It was also hypothesized that watching the news would increase blood pressure (BP), vascular stiffness (VS), and heart rate (HR). METHODS: In a randomized, controlled, crossover design, 18 young (21 ± 1 yrs, 9 female, 9 male) healthy participants (172.6 ± 9.9 cm, 69 ± 18 kg) were assessed for BP, VS, HR, HRV, and POMS before and after watching an episode of BR or the News matched for time (∼27 mins). RESULTS: A significant interaction effect on POMS scores were observed for, anxiety (p = 0.01), anger (p = 0.008), depression (p = 0.003), fatigue (p = 0.001), and confusion (p = 0.01) domains after watching BR. The LF/HF ratio, an HRV marker of sympathovagal balance, was significantly lower after watching BR (p = 0.04). There were no significant time, condition, or interaction effects on systolic BP, mean arterial pressure, and diastolic BP. CONCLUSION: The "Bob Ross Effect" reduces overall mood disturbance, though appears to exert little influence on the cardiovascular system in this acute paradigm.