Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader-Willi Syndrome.

The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.

Effects of high-intensity interval training on fatigue and quality of life in testicular cancer survivors.

BACKGROUND: Testicular cancer survivors (TCS) are at increased risk of cancer-related fatigue (CRF), psychosocial impairment, and poor mental health-related quality of life (HRQoL). Here, we examine the effects of high-intensity interval training (HIIT) on patient-reported outcomes (PROs) in TCS. Secondarily, we explore cardiorespiratory fitness as a mediator of intervention effects and select baseline characteristics as moderators of intervention effects. METHODS: TCS (n = 63) were randomly assigned to 12 weeks of supervised HIIT or usual care (UC). PROs included CRF, depression, anxiety, stress, self-esteem, sleep quality, and HRQoL assessed at baseline, post-intervention, and 3-month follow-up. RESULTS: TCS (median 7 years postdiagnosis) completed 99% of training sessions and achieved 98% of target training intensity. ANCOVA revealed that, compared to UC, HIIT significantly improved post-intervention CRF (p = 0.003), self-esteem (p = 0.029), and multiple HRQoL domains (ps ≤ 0.05). Effects on CRF (p = 0.031) and vitality (p = 0.015) persisted at 3-month follow-up. Cardiorespiratory fitness changes mediated CRF and HRQoL improvements. CRF effects were larger for TCS with an inactive lifestyle, lower fitness, higher testosterone, and clinical fatigue at baseline. CONCLUSIONS: HIIT significantly improves CRF and HRQoL in TCS. Mediation by cardiorespiratory fitness and moderation by clinical characteristics suggests opportunities for targeted exercise interventions to optimise PROs in TCS.

Effects of high-intensity aerobic interval training on cardiovascular disease risk in testicular cancer survivors: A phase 2 randomized controlled trial.

BACKGROUND: Testicular cancer survivors (TCS) have an increased risk of treatment-related cardiovascular disease (CVD), which may limit their overall survival. We evaluated the effects of high-intensity aerobic interval training (HIIT) on traditional and novel CVD risk factors and surrogate markers of mortality in a population-based sample of TCS. METHODS: This phase 2 trial (ClinicalTrials.gov identifier NCT02459132) randomly assigned 63 TCS to usual care (UC) or 12 weeks of supervised HIIT (ie, alternating periods of vigorous-intensity and light-intensity aerobic exercise). The primary outcome was peak aerobic fitness (VO2peak ) assessed via a treadmill-based maximal cardiorespiratory exercise test. Secondary endpoints included CVD risk (eg, Framingham Risk Score), arterial health, parasympathetic nervous system function, and blood-based biomarkers. RESULTS: Postintervention VO2peak data were obtained for 61 participants (97%). HIIT participants attended 99% of the exercise sessions and achieved 98% of the target exercise intensity. Analysis of covariance demonstrated that HIIT was superior to UC for improving VO2peak (adjusted between-group mean difference, 3.7 mL O2 /kg/min; 95% confidence interval, 2.4-5.1 [P<.001]) and multiple secondary outcomes including CVD risk (P = .011), arterial thickness (P<.001), arterial stiffness (P<.001), postexercise parasympathetic reactivation (P = .001), inflammation (P = .045), and low-density lipoprotein (P = .014). Overall, HIIT reduced the prevalence of modifiable CVD risk factors by 20% compared with UC. CONCLUSIONS: This randomized trial provides the first evidence that HIIT improves cardiorespiratory fitness, multiple pathways of CVD risk, and surrogate markers of mortality in TCS. These findings have important implications for the management of TCS. Further research concerning the long-term effects of HIIT on CVD morbidity and mortality in TCS is warranted. Cancer 2017;123:4057-65. © 2017 American Cancer Society.

Hindlimb unweighting does not alter vasoconstrictor responsiveness and nitric oxide-mediated inhibition of sympathetic vasoconstriction.

KEY POINTS: Physical inactivity increases the risk of cardiovascular disease and may alter sympathetic nervous system control of vascular resistance. Hindlimb unweighting (HU), a rodent model of physical inactivity, has been shown to diminish sympathetic vasoconstrictor responsiveness and reduce NO synthase expression in isolated skeletal muscle blood vessels. Our understanding of the effects of HU on sympathetic vascular regulation in vivo is very limited. The present findings demonstrate that HU did not alter sympathetic vasoconstrictor responsiveness and NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. This study suggests that short-term physical inactivity does not alter in vivo sympathetic vascular control in the skeletal muscle vascular bed at rest and during contraction. ABSTRACT: We tested the hypothesis that physical inactivity would increase sympathetic vasoconstrictor responsiveness and diminish NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. Sprague-Dawley rats (n = 33) were randomly assigned to sedentary time control (S) or hindlimb unweighted (HU) groups for 21 days. Following the intervention, rats were anaesthetized and instrumented for measurement of arterial blood pressure and femoral artery blood flow and stimulation of the lumbar sympathetic chain. The percentage change of femoral vascular conductance (%FVC) in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after NO synthase blockade with l-NAME (5 mg kg i.v.). Sympathetic vasoconstrictor responsiveness was not different (P > 0.05) in S and HU rats at rest (S, 2 Hz, -26 ± 8% and 5 Hz, -46 ± 12%; and HU, 2 Hz, -29 ± 9% and 5 Hz, -51 ± 10%) and during contraction (S, 2 Hz, -10 ± 7% and 5 Hz, -23 ± 11%; and HU, 2 Hz, -9 ± 5% and 5 Hz, -22 ± 7%). Nitric oxide synthase blockade caused a similar increase (P > 0.05) in sympathetic vasoconstrictor responsiveness in HU and S rats at rest (S, 2 Hz, -41 ± 7% and 5 Hz, -58 ± 8%; and HU, 2 Hz, -43 ± 6% and 5 Hz, -63 ± 8%) and during muscle contraction (S, 2 Hz, -15 ± 6% and 5 Hz, -31 ± 11%; and HU, 2 Hz, -12 ± 5% and 5 Hz, -29 ± 8%). Skeletal muscle NO synthase expression and ACh-mediated vasodilatation were also not different between HU and S rats. These data suggest that HU does not alter sympathetic vasoconstrictor responsiveness and NO-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle.

Vascular effects of aerobic exercise training in rat adult offspring exposed to hypoxia-induced intrauterine growth restriction.

KEY POINTS: Prenatal hypoxia, one of the most common consequences of complicated pregnancies, leads to intrauterine growth restriction (IUGR) and impairs later-life endothelium-dependent vascular function. Early interventions are needed to ultimately reduce later-life risk for cardiovascular disease. Aerobic exercise training has been shown to prevent cardiovascular diseases. Whether exercise can be used as an intervention to reverse the vascular phenotype of this susceptible population is unknown. Aerobic exercise training enhanced endothelium-derived hyperpolarization-mediated vasodilatation in gastrocnemius muscle arteries in male IUGR offspring, and did not improve nitric oxide-mediated vasodilatation in IUGR offspring. Understanding the mechanisms by which exercise impacts the cardiovascular system in a susceptible population and the consideration of sexual dimorphism is essential to define whether exercise could be used as a preventive strategy in this population. ABSTRACT: Hypoxia in utero is a critical insult causing intrauterine growth restriction (IUGR). Adult offspring born with hypoxia-induced IUGR have impaired endothelium-dependent vascular function. We tested whether aerobic exercise improves IUGR-induced endothelial dysfunction. Pregnant Sprague-Dawley rats were exposed to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational day 15 to 21. Male and female offspring from normoxic and hypoxic (IUGR) pregnancies were randomized at 10 weeks of age to either an exercise-trained or sedentary group. Exercise-trained rats ran on a treadmill for 30 min at 20 m min(-1) , 5 deg gradient, 5 days week(-1) , for 6 weeks. Concentration-response curves to phenylephrine and methylcholine were performed in second order mesenteric and gastrocnemius muscle arteries, in the presence or absence of l-NAME (100 µm), MnTBAP (peroxynitrite scavenger; 10 µm), apamin (0.1 µm) and TRAM-34 (an intermediate-conductance calcium-activated potassium channel blocker; 10 µm), or indomethacin (5 µm). In adult male IUGR offspring, prenatal hypoxia had no effect on total vasodilator responses in either vascular bed. Aerobic exercise training in IUGR males, however, improved endothelium-derived hyperpolarization (EDH)-mediated vasodilatation in gastrocnemius muscle arteries. Female IUGR offspring had reduced NO-mediated vasodilatation in both vascular beds, along with decreased total vasodilator responses and increased prostaglandin-mediated vasoconstriction in gastrocnemius muscle arteries. In contrast to males, aerobic exercise training in IUGR female offspring had no effect on either vascular bed. Exercise may not prove to be a beneficial therapy for specific vascular pathways affected by prenatal hypoxia, particularly in female offspring.

Exercise training augments neuronal nitric oxide synthase-mediated inhibition of sympathetic vasoconstriction in contracting skeletal muscle of rats.

We tested the hypothesis that exercise training would increase neuronal nitric oxide synthase (nNOS)-mediated inhibition of sympathetic vasoconstriction in resting and contracting skeletal muscle. Sprague-Dawley rats (n = 18) were randomized to sedentary or exercise-trained (40 m min(-1), 5° grade; 5 days week(-1) for 4 weeks) groups. Following completion of sedentary behaviour or exercise training, rats were anaesthetized and instrumented with a brachial artery catheter, femoral artery flow probe and stimulating electrodes on the lumbar sympathetic chain. The percentage change of femoral vascular conductance (%FVC) in response to sympathetic chain stimulations delivered at 2 and 5 Hz was determined at rest and during triceps surae muscle contraction before (control) and after selective nNOS blockade with S-methyl-l-thiocitrulline (SMTC, 0.6 mg kg(-1), i.v.) and subsequent non-selective NOS blockade with l-NAME (5 mg kg(-1), i.v.; SMTC + l-NAME). At rest, sympathetic vasoconstrictor responsiveness was greater (P < 0.05) in exercise-trained compared to sedentary rats in control, SMTC and SMTC + l-NAME conditions. During contraction, the constrictor response was not different (P > 0.05) between exercise trained (2 Hz: -11 ± 4%FVC; 5 Hz: -21 ± 5%FVC) and sedentary rats (2 Hz: -7 ± 6%FVC; 5 Hz: -18 ± 10%FVC) in control conditions. SMTC augmented (P < 0.05) sympathetic vasoconstriction in sedentary and exercise-trained rats; however, sympathetic vasoconstrictor responsiveness was greater (P < 0.05) in exercise-trained (2 Hz: -27 ± 5%FVC; 5 Hz: -39 ± 5%FVC) compared to sedentary (2 Hz: -17 ± 6%FVC; 5 Hz: -27 ± 8%FVC) rats during selective nNOS inhibition. SMTC + l-NAME further augmented (P < 0.05) sympathetic vasoconstrictor responsiveness by a similar magnitude (P > 0.05) in exercise-trained and sedentary rats. These data demonstrate that exercise training augmented nNOS-mediated inhibition of sympathetic vasoconstriction in contracting muscle.

Short-term exercise training enhances functional sympatholysis through a nitric oxide-dependent mechanism.

We tested the hypothesis that short-term mild- (M) and heavy-intensity (H) exercise training would enhance sympatholysis through a nitric oxide (NO)-dependent mechanism. Sprague-Dawley rats (n = 36) were randomly assigned to sedentary (S) or to M (20 m min(-1) 5% gradient) or H exercise training groups (40 m min(-1) 5% gradient). Rats assigned to M and H groups trained on 5 days week(-1) for 4 weeks, with the volume of training being matched between groups. Rats were anaesthetized and instrumented for stimulation of the lumbar sympathetic chain and the measurement of arterial blood pressure and femoral artery blood flow. The triceps surae muscle group was stimulated to contract rhythmically at 30 and 60% of maximal contractile force (MCF). The percentage change of femoral vascular conductance (%FVC) in response to sympathetic stimulation delivered at 2 and 5 Hz was determined at rest and during contraction at 30 and 60% MCF. The vascular response to sympathetic stimulation was reduced as a function of MCF in all rats (P < 0.05). At 30% MCF, the magnitude of sympatholysis (%FVC rest - contraction; %FVC) was greater in H compared with M and S groups (%FVC at 2 Hz, S, 9 ± 5; M, 11 ± 8; and H, 18 ± 7; and %FVC at 5 Hz, S, 6 ± 6; M, 12 ± 9; and H, 18 ± 7; P < 0.05) and was greater in H and M compared with S at 60% MCF (%FVC at 2 Hz, S, 15 ± 5; M, 25 ± 3; and H, 36 ± 6; and %FVC at 5 Hz, S, 22 ± 6; M, 33 ± 9; and H, 39 ± 9; P < 0.05). Blockade of NO synthase did not alter the magnitude of sympatholysis in S during contraction at 30 or 60% MCF. In contrast, NO synthase inhibition diminished sympatholysis in H at 30% MCF and in M and H at 60% MCF (P < 0.05). The present findings indicate that short-term exercise training augments sympatholysis in a training-intensity-dependent manner and through an NO-dependent mechanism.

Short-term exercise training augments 2-adrenoreceptor-mediated sympathetic vasoconstriction in resting and contracting skeletal muscle.

We hypothesized that exercise training (ET) would alter α2-adrenoreceptor-mediated sympathetic vasoconstriction. Sprague-Dawley rats (n = 30) were randomized to sedentary (S), mild- (M) or heavy-intensity (H) treadmill ET groups (5 days per week for 4 weeks). Following the ET component of the study, rats were anaesthetized, and instrumented for lumbar sympathetic chain stimulation, triceps surae muscle contraction and measurement of femoral vascular conductance (FVC). The percentage change of FVC in response to sympathetic stimulation was determined at rest and during contraction in control, α2 blockade (yohimbine) and combined α2 + nitric oxide (NO) synthase (NOS) blockade (N-nitro-L-arginine methyl ester hydrochloride, L-NAME) conditions. ET augmented (P < 0.05) sympathetic vasoconstrictor responses at rest and during contraction. Yohimbine reduced (P < 0.05) the vasoconstrictor response in ET rats at rest (M: 2 Hz: 8 ± 2%, 5 Hz: 9 ± 4%; H: 2 Hz: 14 ± 5%, 5 Hz: 11 ± 6%) and during contraction (M: 2 Hz: 9 ± 2%, 5 Hz: 9 ± 5%; H: 2 Hz: 8 ± 3%, 5 Hz: 6 ± 6%) but did not change the response in S rats. The addition of L-NAME caused a larger increase (P < 0.05) in the vasoconstrictor response in ET than in S rats at rest (2 Hz: S: 8 ± 2%, M: 15 ± 3%, H: 23 ± 7%; 5 Hz: S: 8 ± 5%, M: 15 ± 3%, H: 17 ± 5%) and during contraction (2 Hz: S: 9 ± 3%, M: 18 ± 3%, H: 22 ± 6%; 5 Hz: S: 9 ± 5%, M: 22 ± 4%, H:26 ± 9%). Sympatholysis was greater (P < 0.05) in ET than in S rats. Blockade of α2-adrenoreceptors and NOS reduced (P < 0.05) sympatholysis in ET rats, but had no effect on sympatholysis in S rats. In conclusion, ET increased α2-mediated vasoconstriction at rest and during contraction.

Short-term exercise training augments sympathetic vasoconstrictor responsiveness and endothelium-dependent vasodilation in resting skeletal muscle.

We tested the hypotheses that 4 wk of exercise training would diminish the magnitude of vasoconstriction in response to sympathetic nerve stimulation and augment endothelium-dependent vasodilation (EDD) in resting skeletal muscle in a training intensity-dependent manner. Sprague-Dawley rats were randomly assigned to sedentary time-control (S), mild- (M; 20 m/min, 5% grade), or heavy-intensity (H; 40 m/min, 5% grade) treadmill exercise groups. Animals trained 5 days/wk for 4 wk with training volume matched between groups. Rats were anesthetized and instrumented for study 24 h after the last training session. Arterial pressure and femoral artery blood flow were measured, and femoral vascular conductance (FVC) was calculated. Lumbar sympathetic chain stimulation was delivered continuously at 2 Hz and in patterns at 20 and 40 Hz. EDD was assessed by the vascular response to intra-arterial bolus injections of ACh. The response (% change FVC) to sympathetic stimulation increased (P < 0.05) in a training intensity-dependent manner at 2 Hz (S: -20.2 ± 9.8%, M: -34.0 ± 6.7%, and H: -44.9 ± 2.0%), 20 Hz (S: -22.0 ± 10.6%, M: -31.2 ± 8.4%, and H: -42.8 ± 5.9%), and 40 Hz (S: H -24.5 ± 8.5%, M: -35.1 ± 8.9%, H: -44.9 ± 6.5%). The magnitude of EDD also increased in a training intensity-dependent manner (P < 0.05). These data demonstrate that short-term exercise training augments the magnitude of vasoconstriction in response to sympathetic stimulation and EDD in resting skeletal muscle in a training intensity-dependent manner.

Does sympathetic vasoconstriction contribute to metabolism: Perfusion matching in exercising skeletal muscle?

The process of matching skeletal muscle blood flow to metabolism is complex and multi-factorial. In response to exercise, increases in cardiac output, perfusion pressure and local vasodilation facilitate an intensity-dependent increase in muscle blood flow. Concomitantly, sympathetic nerve activity directed to both exercising and non-active muscles increases as a function of exercise intensity. Several studies have reported the presence of tonic sympathetic vasoconstriction in the vasculature of exercising muscle at the onset of exercise that persists through prolonged exercise bouts, though it is blunted in an exercise-intensity dependent manner (functional sympatholysis). The collective evidence has resulted in the current dogma that vasoactive molecules released from skeletal muscle, the vascular endothelium, and possibly red blood cells produce local vasodilation, while sympathetic vasoconstriction restrains vasodilation to direct blood flow to the most metabolically active muscles/fibers. Vascular smooth muscle is assumed to integrate a host of vasoactive signals resulting in a precise matching of muscle blood flow to metabolism. Unfortunately, a critical review of the available literature reveals that published studies have largely focused on bulk blood flow and existing experimental approaches with limited ability to reveal the matching of perfusion with metabolism, particularly between and within muscles. This paper will review our current understanding of the regulation of sympathetic vasoconstriction in contracting skeletal muscle and highlight areas where further investigation is necessary.

Left ventricular systolic and diastolic function during tilt-table positioning and passive heat stress in humans.

The ventricular response to passive heat stress has predominantly been studied in the supine position. It is presently unclear how acute changes in venous return influence ventricular function during heat stress. To address this question, left ventricular (LV) systolic and diastolic function were studied in 17 healthy men (24.3 ± 4.0 yr; mean ± SD), using two-dimensional transthoracic echocardiography with Doppler ultrasound, during tilt-table positioning (supine, 30° head-up tilt, and 30° head-down tilt), under normothermic and passive heat stress (core temperature 0.8 ± 0.1°C above baseline) conditions. The supine heat stress LV volumetric and functional response was consistent with previous reports. Combining head-up tilt with heat stress reduced end-diastolic (25.2 ± 4.1%) and end-systolic (65.4 ± 10.5%) volume from baseline, whereas heart rate (37.7 ± 2.0%), ejection fraction (9.4 ± 2.4%), and LV elastance (37.7 ± 3.6%) increased, and stroke volume (-28.6 ± 9.4%) and early diastolic inflow (-17.5 ± 6.5%) and annular tissue (-35.6 ± 7.0%) velocities were reduced. Combining head-down tilt with heat stress restored end-diastolic volume, whereas LV elastance (16.8 ± 3.2%), ejection fraction (7.2 ± 2.1%), and systolic annular tissue velocities (22.4 ± 5.0%) remained elevated above baseline, and end-systolic volume was reduced (-15.3 ± 3.9%). Stroke volume and the early and late diastolic inflow and annular tissue velocities were unchanged from baseline. This investigation extends previous work by demonstrating increased LV systolic function with heat stress, under varied levels of venous return, and highlights the preload dependency of early diastolic function during passive heat stress.

Sympathetic vasoconstriction in skeletal muscle: modulatory effects of aging, exercise training, and sex.

The sympathetic nervous system (SNS) is a critically important regulator of the cardiovascular system. The SNS controls cardiac output and its distribution, as well as peripheral vascular resistance and blood pressure at rest and during exercise. Aging is associated with increased blood pressure and decreased skeletal muscle blood flow at rest and in response to exercise. The mechanisms responsible for the blunted skeletal muscle blood flow response to dynamic exercise with aging have not been fully elucidated; however, increased muscle sympathetic nerve activity (MSNA), elevated vascular resistance, and a decline in endothelium-dependent vasodilation are commonly reported in older adults. In contrast to aging, exercise training has been shown to reduce blood pressure and enhance skeletal muscle vascular function. Exercise training has been shown to enhance nitric oxide-dependent vascular function and may improve the vasodilatory capacity of the skeletal muscle vasculature; however, surprisingly little is known about the effect of exercise training on the neural control of circulation. The control of blood pressure and skeletal muscle blood flow also differs between men and women. Blood pressure and MSNA appear to be lower in young women than in men. However, females experience a larger increase in MSNA with aging compared with males. The mechanism(s) underlying the altered SNS control of vascular function in females remains to be determined. Novelty: This review summarizes our current understanding of the effects of aging, exercise training, and sex on sympathetic vasoconstriction at rest and during exercise. Areas where additional research is needed are also identified.

Effects of sex and exercise training on ß-adrenoreceptor-mediated opposition of evoked sympathetic vasoconstriction in resting and contracting muscle of rats.

This study investigated the hypothesis that ß-adrenoreceptor-mediated inhibition of sympathetic vasoconstriction would be enhanced in female compared with male rats, and that endurance exercise training would augment ß-adrenoreceptor-mediated inhibition of sympathetic vasoconstriction in male and female rats. Sprague-Dawley rats were randomized into sedentary (male: n = 7; female: n = 8) and exercise-trained (male: n = 9; female: n = 9) groups. Following 4 wk of exercise training or being sedentary, rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain, muscle contraction and measurement of arterial blood pressure and femoral artery blood flow (FBF). Femoral vascular conductance (FVC) was calculated as FBF/mean arterial pressure. The percentage change of FVC in response to sympathetic stimulation delivered at 2 and 5 Hz was measured at rest and during contraction of the triceps surae muscles before and after ß-adrenoreceptor blockade (propranolol: 0.075 mg·kg-1 iv). We found that, at rest, ß-adrenoreceptor blockade decreased (main effect of drug, 2 Hz: P < 0.001; 5 Hz: P < 0.001) sympathetic vasoconstriction. During contraction, sympathetic vasoconstrictor responsiveness was lower (main effect of sex, 2 Hz: P = 0.001; 5 Hz: P = 0.023) in female compared with male rats, and sympatholysis was enhanced (main effect of sex, 2 Hz: P = 0.001; 5 Hz: P < 0.001) in female rats. ß-adrenoreceptor blockade decreased (main effect of drug, 2 Hz: P = 0.049; 5 Hz: P < 0.001) evoked sympathetic vasoconstriction in contracting muscle. The present study demonstrated that ß-adrenoreceptors do not blunt sympathetic vasoconstriction in resting or contracting skeletal muscle of male or female rats. Sympatholysis was enhanced in female rats; however, this was not attributable to ß-adrenoreceptor-mediated blunting of sympathetic vasoconstriction.NEW & NOTEWORTHY ß-adrenoreceptors do not inhibit sympathetic vasoconstriction in resting or contracting muscle of male or female rats, regardless of training status. Sympatholysis was enhanced in female, compared to male rats; however, ß-adrenoreceptors were not responsible for the enhanced sympatholysis. These findings indicate that ß-adrenoreceptors do not contribute to the regulation of sympathetic vasoconstriction in resting and contracting skeletal muscle and suggest that ß-adrenoreceptors do not underlie sex differences in the neural control of the circulation.

Increased left ventricular twist, untwisting rates, and suction maintain global diastolic function during passive heat stress in humans.

Left ventricular (LV) systolic function increases with passive heat stress (HS); however, less is known about diastolic function. Eight healthy subjects (24.0 +/- 2.0 yr of age) underwent whole body passive heating approximately 1 degrees C above baseline (BL). Cardiac magnetic resonance imaging was used to measure biventricular volumes, function, filling velocities, volumetric flow rates, and LV twist and strain at BL and after 45 min of HS. Passive heating reduced left atrial volume (-17.6 +/- 11.7 ml, P < 0.05), right and LV end-diastolic volumes (-22.7 +/- 11.0 and -25.7 +/- 24.9 ml, respectively; P < 0.05), and LV stroke volume (-6.7 +/- 6.8 ml, P < 0.05) from BL. LV ejection fraction (EF), end-systolic elastance, septal and lateral mitral annular systolic velocities, circumferential strain, and peak LV twist increased with HS (P < 0.05). Right ventricular stroke volume, EF, and systolic tissue velocities were unchanged with HS (P > 0.05). Early LV diastolic tissue and blood velocities and strain rates were maintained with HS, whereas untwisting rate increased significantly from 166.4 +/- 46.9 to 268.7 +/- 76.8 degrees /s (P < 0.05). The major novel finding of this study was that, secondary to an increase in peak LV twist and untwisting rate, early diastolic blood and tissue velocities and strain rates are maintained despite a reduction in filling pressure.

Kinetics of VO2 limb blood flow and regional muscle deoxygenation in young adults during moderate intensity, knee-extension exercise.

The kinetics of pulmonary O(2) uptake (VO(2p)), limb blood flow (LBF) and deoxygenation (DeltaHHb) of the vastus lateralis (VL) and vastus medialis (VM) muscles during the transition to moderate-intensity knee-extension exercise (MOD) was examined. Seven males (27 +/- 5 years; mean +/- SD) performed repeated step transitions (n = 4) from passive exercise to MOD. Breath by breath VO(2p) femoral artery LBF, and VL and VM muscle DeltaHHb were measured, respectively, by mass spectrometer and volume turbine, Doppler ultrasound and near-infrared spectroscopy. Phase 2 VO(2p), LBF, and HHb data were fit with a mono-exponential model. The time constant (tau) of the VO(2p) and LBF response were not different (tauVO(2p), 24 +/- 6 s; tauLBF, 23 +/- 8 s). The DeltaHHb response did not differ between VL and VM in amplitude (VL 6.97 +/- 4.22 a.u.; VM 7.24 +/- 3.99 a.u.), time delay (DeltaHHb(TD): VL 17 +/- 2 s; VM 15 +/- 1 s), time constant (tauDeltaHHb: VL 11 +/- 6 s; VM 13 +/- 4 s), or effective time constant [tau'DeltaHHb (= DeltaHHb(TD) + tauDeltaHHb): VL 28 +/- 7 s; VM 28 +/- 4 s]. Adjustments in DeltaHHb in VL and VM depict a similar balance of regional O(2) delivery and utilization within the quadriceps muscle group. The tau'DeltaHHb and tauVO(2p) were similar, however, the DeltaHHb displayed an "overshoot" relative to the steady-state levels reflecting a slower alteration of microvascular blood flow (O(2) delivery) relative to O(2) utilization, necessitating a greater reliance on O(2) extraction.

Differences in exercise limb blood flow and muscle deoxygenation with age: contributions to O2 uptake kinetics.

The adjustments of pulmonary oxygen uptake V O2p limb blood flow (LBF) and muscle deoxygenation (ΔHHb) were examined during transitions to moderate-intensity, knee-extension exercise in seven older (OA; 71 ± 7 year) and seven young (YA; 26 ± 3 year) men. YA and OA performed repeated step transitions from an active baseline (3 W; 100 g) to a similar relative intensity of ~80% estimated lactate threshold (θ(L)), and YA also performed the same absolute work rate as the OA (24 W, 800 g). Breath-by-breath V O2p femoral artery LBF (Doppler ultrasound) and muscle HHb (near-infrared spectroscopy) were measured. Phase 2V O2p LBF, and ΔHHb data were fit with a mono-exponential model. τ V O2p was greater in OA (58 ± 21 s) than YA(80%) (31 ± 9 s) and YA(24W) (29 ± 11 s). The increase in LBF per increase in V O2p was not different between groups (5.3-5.8 L min(-1)/L min(-1)); however, the τLBF was greater in OA (44 ± 19 s) than YA(24W) (18 ± 7 s). The overall adjustment in ΔHHb (τ'ΔHHb) was not different between OA and YA, but was faster than τ V O2p in OA. This faster τ'ΔHHb than τ V O2p resulted in an "overshoot" of the normalized ΔHHb/Δ V O2p response relative to the steady state level that was significantly greater in OA compared with YA suggesting that the adjustment of microvascular blood flow is slowed in OA thereby requiring a greater reliance on O(2) extraction during the transition to exercise.

Effect of acute dietary nitrate supplementation on sympathetic vasoconstriction at rest and during exercise.

Dietary nitrate ( NO3- ) supplementation has been shown to reduce resting blood pressure. However, the mechanism responsible for the reduction in blood pressure has not been identified. Dietary NO3- supplementation may increase nitric oxide (NO) bioavailability, and NO has been shown to inhibit sympathetic vasoconstriction in resting and contracting skeletal muscle. Therefore, the purpose of this study was to investigate the hypothesis that acute dietary NO3- supplementation would attenuate sympathetic vasoconstrictor responsiveness at rest and during exercise. In a double-blind randomized crossover design, 12 men (23 ± 5 yr) performed a cold-pressor test (CPT) at rest and during moderate- and heavy-intensity alternate-leg knee-extension exercise after consumption of NO3- rich beetroot juice (~12.9 mmol NO3- ) or a NO3- -depleted placebo (~0.13 mmol NO3- ). Venous blood was sampled before and 2.5 h after the consumption of beetroot juice for the measurement of total plasma nitrite/ NO3- [NOx]. Beat-by-beat blood pressure was measured by Finometer. Leg blood flow was measured at the femoral artery via Doppler ultrasound, and leg vascular conductance (LVC) was calculated. Sympathetic vasoconstrictor responsiveness was calculated as the percentage decrease in LVC in response to the CPT. Total plasma [NOx] was greater (P < 0.001) in the NO3- (285 ± 120 µM) compared with the placebo (65 ± 30 µM) condition. However, mean arterial blood pressure and plasma catecholamines were not different (P > 0.05) between NO3- and placebo conditions at rest or during moderate- and heavy-intensity exercise. Sympathetic vasoconstrictor responsiveness (Δ% LVC) was not different (P > 0.05) between NO3- and placebo conditions at rest ( NO3- : -33 ± 10%; placebo: -35 ± 11%) or during moderate ( NO3- : -18 ± 8%; placebo: -20 ± 10%)- and heavy ( NO3- : -12 ± 8%; placebo: -11 ± 9%)-intensity exercise. These data demonstrate that acute dietary NO3- supplementation does not alter sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males. NEW & NOTEWORTHY Dietary nitrate may increase nitric oxide bioavailability, and nitric oxide has been shown to attenuate sympathetic vasoconstriction in resting and contracting skeletal muscle and enhance functional sympatholysis. However, the effect of dietary nitrate on sympathetic vasoconstrictor responsiveness is unknown. Acute dietary nitrate supplementation did not alter blood pressure or sympathetic vasoconstrictor responsiveness at rest or during exercise in young healthy males.

ß-Adrenoreceptors do not oppose sympathetic vasoconstriction in resting and contracting skeletal muscle of male rats.

Sympathetic nervous system (SNS) vasoconstriction is primarily achieved through the binding of norepinephrine (NE) to α-adrenoreceptors. However, NE may also bind to ß-adrenoreceptors and cause vasodilation that may oppose/blunt SNS-mediated vasoconstriction. Therefore, this study investigated the hypothesis that ß-adrenoreceptor-mediated vasodilation opposes evoked vasoconstriction in resting and contracting skeletal muscle. Male (n = 9) Sprague-Dawley rats were anesthetized and surgically instrumented for stimulation of the lumbar sympathetic chain and measurement of arterial blood pressure and femoral artery blood flow. The percentage change of femoral vascular conductance in response to sympathetic chain stimulation delivered at 2 and 5 Hz was determined at rest and during triceps surae skeletal muscle contraction before (control) and after ß-adrenoreceptor blockade (propranolol; 0.075 mg·kg-1, intravenously). ß-Adrenoreceptor blockade did not alter (P > 0.05) baseline hemodynamics or the hyperemic response to exercise. At the 2 Hz stimulation frequency, sympathetic vasoconstriction was similar (P > 0.05) in control and ß-blockade conditions in resting (control, -34% ± 6%; ß-blockade, -33% ± 8%) and contracting (control, -16% ± 6%; ß-blockade, -14% ± 7%) muscle. At the 5 Hz stimulation frequency, sympathetic vasoconstrictor responsiveness was reduced (main effect of drug, P < 0.05) following ß-blockade (rest: control, -52% ± 7%; ß-blockade, -51% ± 9%; contraction: control, -32% ± 11%; ß-blockade, -29% ± 13%). Novelty These data indicate that ß-adrenoreceptor blockade did not augment sympathetic vasoconstriction at rest or during exercise. The study demonstrates that ß-adrenoreceptors do not oppose evoked sympathetic vasoconstriction in resting or contracting skeletal muscle or contribute to functional sympatholysis.

Fat distribution and end-expiratory lung volume in lean and obese men and women.

BACKGROUND: Although obesity significantly reduces end-expiratory lung volume (EELV), the relationship between EELV and detailed measures of fat distribution has not been studied in obese men and women. To investigate, EELV and chest wall fat distribution (ie, rib cage, anterior subcutaneous abdominal fat, posterior subcutaneous fat, and visceral fat) were measured in lean men and women (ie, < 25% body fat) and obese men and women (ie, > 30% body fat). METHODS: All subjects underwent pulmonary function testing, hydrostatic weighing, and MRI scans. Data were analyzed for the men and women separately by independent t test, and the relationships between variables were determined by regression analysis. RESULTS: All body composition measurements were significantly different among the lean and obese men and women (p < 0.001). However, with only a few exceptions, fat distribution was similar among the lean and obese men and women (p > 0.05). The mean EELV was significantly lower in the obese men (39 +/- 6% vs 46 +/- 4% total lung capacity [TLC], respectively; p < 0.0005) and women (40 +/- 4% vs 53 +/- 4% TLC, respectively; p < 0.0001) compared with lean control subjects. Many estimates of body fat were significantly correlated with EELV for both men and women. CONCLUSIONS: In both men and women, the decrease in EELV with obesity appears to be related to the cumulative effect of increased chest wall fat rather than to any specific regional chest wall fat distribution. Also, with only a few exceptions, relative fat distribution is markedly similar between lean and obese subjects.