Dual endothelin receptor antagonism increases resting energy expenditure in people with increased adiposity.

Increased adiposity is associated with dysregulation of the endothelin system, both of which increase the risk of cardiovascular disease (CVD). Preclinical data indicate that endothelin dysregulation also reduces resting energy expenditure (REE). The objective was to test the hypothesis that endothelin receptor antagonism will increase REE in people with obesity compared with healthy weight individuals. Using a double blind, placebo-controlled, crossover design, 32 participants [healthy weight (HW): n = 16, BMI: 21.3 ± 2.8 kg/m2, age: 26 ± 7 yr and overweight/obese (OB): n = 16, BMI: 33.5 ± 9.5 kg/m2, age: 31 ± 6 yr] were randomized to receive either 125 mg of bosentan (ETA/B antagonism) or placebo twice per day for 3 days. Breath-by-breath gas exchange data were collected and REE was assessed by indirect calorimetry. Venous blood samples were analyzed for concentrations of endothelin-1 (ET-1). Treatment with bosentan increased plasma ET-1 in both OB and HW groups. Within the OB group, the changes in absolute REE (PLA: -77.6 ± 127.6 vs. BOS: 72.2 ± 146.6 kcal/day; P = 0.046). The change in REE was not different following either treatment in the HW group. Overall, absolute plasma concentrations of ET-1 following treatment with bosentan were significantly associated with kcal/day of fat (r = 0.488, P = 0.005), percentage of fat utilization (r = 0.415, P = 0.020), and inversely associated with the percentage of carbohydrates (r = -0.419, P = 0.019), and respiratory exchange ratio (r = -0.407, P = 0.023). Taken together, these results suggest that modulation of the endothelin system may represent a novel therapeutic approach to increase both resting metabolism and caloric expenditure, and reduce CVD risk in people with increased adiposity.NEW & NOTEWORTHY Findings from our current translational investigation demonstrate that dual endothelin A/B receptor antagonism increases total REE in overweight/obese individuals. These results suggest that modulation of the endothelin system may represent a novel therapeutic target to increase both resting metabolism and caloric expenditure, enhance weight loss, and reduce CVD risk in seemingly healthy individuals with elevated adiposity.

Adequacy of Daily Fluid Intake Volume Can Be Identified From Urinary Frequency and Perceived Thirst in Healthy Adults.

Objective: Achieving and maintaining an optimal level of hydration has significant implications for both acute and chronic health, yet many hydration assessments are not feasible for the general public. Urinary frequency (UF) is a reliable method to self-assess hydration status in healthy individuals, and thirst can provide additional sensory information on adequacy of daily fluid intake volume (DFI). However, threshold values for these indices to detect optimal hydration have not been determined. In this study, we sought to determine threshold values for 24-hour UF and perceived thirst that could accurately distinguish between optimal and suboptimal hydration states.Methods: Thirty-two healthy adults (age 22 ± 3 years, body mass index 24.9 ± 4.1 kg/m2) collected urine over 24 hours on four separate occasions, where UF was recorded as well as thirst at each void using a numbered perceptual scale. Using urine osmolality as the criterion standard, all samples were either classified as representing an optimal (≤500 mOsm·kg-1) or suboptimal hydration status (>500 mOsm·kg-1).Results: A 24-hour UF ≤6 was able to detect suboptimal hydration with good accuracy (area under the curve [AUC] 0.815) and a 24-hour average perceived thirst rating > 3 ("a little thirsty") could detect it with reasonable accuracy (AUC 0.725). In addition, a UF ≤4 had a considerably higher positive likelihood ratio to detect suboptimal hydration versus a UF ≤6 (9.03 versus 2.18, respectively).Conclusions: These analyses suggest that individuals with a 24-hour UF ≤6 or perceiving themselves to be, on average, "a little thirsty" throughout the day are likely to be suboptimally hydrated and thus underconsuming an adequate DFI.

Oral NaHCO3 Activates a Splenic Anti-Inflammatory Pathway: Evidence That Cholinergic Signals Are Transmitted via Mesothelial Cells.

We tested the hypothesis that oral NaHCO3 intake stimulates splenic anti-inflammatory pathways. Following oral NaHCO3 loading, macrophage polarization was shifted from predominantly M1 (inflammatory) to M2 (regulatory) phenotypes, and FOXP3+CD4+ T-lymphocytes increased in the spleen, blood, and kidneys of rats. Similar anti-inflammatory changes in macrophage polarization were observed in the blood of human subjects following NaHCO3 ingestion. Surprisingly, we found that gentle manipulation to visualize the spleen at midline during surgical laparotomy (sham splenectomy) was sufficient to abolish the response in rats and resulted in hypertrophy/hyperplasia of the capsular mesothelial cells. Thin collagenous connections lined by mesothelial cells were found to connect to the capsular mesothelium. Mesothelial cells in these connections stained positive for the pan-neuronal marker PGP9.5 and acetylcholine esterase and contained many ultrastructural elements, which visually resembled neuronal structures. Both disruption of the fragile mesothelial connections or transection of the vagal nerves resulted in the loss of capsular mesothelial acetylcholine esterase staining and reduced splenic mass. Our data indicate that oral NaHCO3 activates a splenic anti-inflammatory pathway and provides evidence that the signals that mediate this response are transmitted to the spleen via a novel neuronal-like function of mesothelial cells.

Exercise testing in patients with cystic fibrosis-importance of ventilatory parameters.

BACKGROUND: Ventilatory parameters obtained during exercise predict survival in several chronic diseases; however, long-term changes in exercise ventilatory parameters in patients with cystic fibrosis (CF) have yet to be examined and potential differences between sexes in CF are unknown. PURPOSE: We sought to examine the change in exercise ventilatory parameters over time in patients with CF and determine if the change is different between sexes. METHODS: Exercise capacity (VO2 peak) and exercise ventilatory parameters (VE/VO2 peak, VE/VCO2 peak, and VE/VCO2 slope) were determined from a maximal cardio-pulmonary test on a cycle ergometer on two visits separated by 39 ± 16 months in 20 patients with CF (10 female, 10 male). RESULTS: No differences between sexes were observed at visit 1 (all p > 0.05). Overall, exercise ventilatory parameters significantly (p < 0.05) deteriorated between visits, with no change (p > 0.05) in VO2 peak. Moreover, compared to males, female patients exhibited greater deteriorations in VE/VO2 peak (p = 0.001), VE/VCO2 peak (p = 0.002), and VE/VCO2 slope (p = 0.016) between visits. CONCLUSIONS: These data in patients with CF indicate that exercise ventilatory parameters decline over time despite no change in VO2 peak, and female patients exhibit a more rapid deterioration compared to males.

Sildenafil improves vascular endothelial function in patients with cystic fibrosis.

Cystic fibrosis (CF), characterized by defective CFTR function, is associated with multiple systemic complications, including vascular dysfunction. Sildenafil, a phosphodiesterase type 5 inhibitor, not only enhances nitric oxide (NO) metabolism but has been shown to improve CFTR functionality as well. Thus, sildenafil has been proposed as a therapy to improve vascular health in CF; however, its potential therapeutic role has yet to be determined. We sought to investigate the effect of sildenafil on endothelial function in patients with CF. Patients with CF completed a randomized, double-blind, placebo-controlled, crossover study with an acute dose of sildenafil (50 mg) or placebo followed by a 4-wk open-label extension with sildenafil (20 mg/day). Flow-mediated dilation (FMD) was used to evaluate endothelial function before and after treatments. In addition, phosphorylated endothelial NO synthase (pNOS3) and total NOS3 protein expression was determined from endothelial cells that were exposed to plasma from the patients before and after 4 wk of sildenafil treatment. No changes ( P ≥ 0.110) in endothelial function were observed after the acute dose of sildenafil. However, FMD significantly ( P = 0.029) increased after 4 wk of treatment (∆FMD: 1.5 ± 2.2%). Moreover, pNOS3 protein expression significantly ( P = 0.013) increased after 4 wk of treatment (∆pNOS3: 0.31 ± 0.39 arbitrary units) and was associated ( r = 0.593, P = 0.033) with the change in FMD. These data suggest that 4 wk of sildenafil treatment can improve vascular endothelial function in patients with CF, likely through an increase in NOS3 phosphorylation. NEW & NOTEWORTHY Findings from the present study demonstrate, for the first time, significant improvement of endothelial function in patients with cystic fibrosis treated with sildenafil that is associated with greater phosphorylation of endothelial nitric oxide synthase. These results support the use of sildenafil as a potential novel therapy for this patient population.

Scopolamine does not impact declarative and motor memory consolidation across a night of sleep or a day of wakefulness.

It has been proposed that normal waking levels of acetylcholine (ACH) are important for initial memory acquisition, and that decreased ACH is critical for memory consolidation. Sleep is thought to benefit memory consolidation in part due to the predominance of low ACH levels observed during non-rapid eye movement sleep. Here we examined whether sleep and ACH suppression with the cholinergic antagonist scopolamine impact declarative and motor memory consolidation across a night of sleep or a day of wakefulness. Eighty-seven participants trained on a declarative and motor memory task in the morning or evening. Following training, participants were administered a scopolamine (0.4 mg) or placebo capsule. Participants were retested on the tasks 12 h later after a day of wake or a night of sleep. Reducing ACH levels with scopolamine provided no consolidation benefit for either task. Additionally, we found that sleep had a pronounced beneficial effect for declarative, but not motor memory consolidation. Lastly, in an exploratory analysis of the relationship between motivation and memory performance, we found that indices of intrinsic motivation were associated with improved memory acquisition and consolidation. Our findings show that reducing ACH levels after memory acquisition has no impact on the consolidation of declarative or motor memories. Additionally, sleep benefitted declarative memory but not motor memory consolidation, which highlights the interesting, though uncommon, finding that performance on some tasks might not benefit from sleep. Interestingly, the future study of intrinsic motivation may be warranted given its relationship to memory acquisition and consolidation. These findings add to our understanding of how sleep and acetylcholine impact memory consolidation, and may provide some insight about the role of ACH in memory disorders such as Alzheimer's disease.

Spot Sample Urine Specific Gravity Does Not Accurately Represent Small Decreases in Plasma Volume in Resting Healthy Males.

BACKGROUND: Urine specific gravity (USG) is often used to assess hydration status, particularly around athletic competition, but it is unknown whether high USG is indicative of plasma volume (PV) reduction (i.e., hypohydration). We tested the hypothesis that if high USG is reflective of reduced PV, subsequent fluid ingestion would increase PV. PURPOSE: The purpose of this study was to examine 24-hour changes in USG and PV in individuals presenting with high and low spot USG. METHODS: Nineteen healthy males were provided food and water over 24 hours with a total water volume of 35 ml·kg-1 body mass. Absolute PV and blood volume (BV), measured using the CO-rebreathe technique, along with USG were measured before and after a 24-hour intervention period. Based on a preintervention morning spot USG, subjects were post hoc assigned to groups according to USG (≤1.020 or >1.020; low and high USG, respectively). RESULTS: Despite presenting with an elevated spot USG (1.026 ± 0.004), subsequent fluid ingestion over 24 hours did not lead to changes (∆) in PV (-75 ± 234 ml) or BV (-156 ± 370 ml) in the high USG group (p > 0.05). However, a spot USG after the 24-hour intervention in this group decreased (p = 0.018) to a level indicating improved hydration status (1.017 ± 0.007). In the low USG group, there were no changes in PV (-39 ± 274 ml), BV (-82 ± 396 ml), or USG (0.003 ± 0.007) over the 24-hour fluid intervention (all p > 0.05). CONCLUSIONS: Despite a high preintervention USG and subsequent decrease after 24-hour fluid intake, measures of PV and BV were not indicative of this seemingly improved hydration status. This suggests that a highly concentrated spot sample USG and subsequent changes are not accurately representative of PV or BV.

Postsynaptic cutaneous vasodilation and sweating: influence of adiposity and hydration status.

INTRODUCTION: Obesity and hypohydration independently affect postsynaptic endothelial function, but it is unknown if hypohydration affects lean and obese individuals differently. PURPOSE: To examine the effect of hypohydration on postsynaptic cutaneous vasodilation and sweating in men with high and low adiposity (HI- and LO-BF, respectively). METHODS: Ten males with LO-BF and ten with HI-BF were instrumented for forearm microdialysis when euhydrated and hypohydrated. Changes in cutaneous vascular conductance (CVC) with intradermal infusion of sodium nitroprusside (SNP) and methacholine chloride (MCh) were assessed. Local sweat rate (LSR) was simultaneously assessed at the MCh site. At the end of the last dose, maximal CVC was elicited by delivering a maximal dose of SNP for 30 min to both sites with simultaneous local heating at the SNP site. The concentration of drug needed to elicit 50% of the maximal response (EC50) was compared between groups and hydration conditions. RESULTS: When euhydrated, EC50 of MCh-induced CVC was not different between LO- vs. HI-BF [- 3.04 ± 0.12 vs. - 2.98 ± 0.19 log (MCh) M, P = 0.841]. EC50 of SNP-induced CVC was higher in euhydrated HI- vs. LO-BF (- 1.74 ± 0.17 vs. - 2.13 ± 0.06 log (SNP) M, P = 0.034). Within each group, hydration status did not change MCh- or SNP-induced CVC (P > 0.05). LSR was not different between groups or hydration condition (P > 0.05). CONCLUSIONS: These data suggest reduced sensitivity of endothelium-independent vasodilation in individuals with high adiposity when euhydrated. However, hypohydration does not affect cutaneous vasodilation or local sweat rate differently between individuals with low or high adiposity.

Beneficial effects of a daytime nap on verbal memory in adolescents.

This study aimed to examine the sleep-dependent memory consolidation of verbal declarative memory in Chinese adolescents in a naturalistic experimental setting. Thirty-nine healthy boarding school students (ages 15-18, 70% female) were randomized to either a one-hour afternoon nap or wake group between the baseline and the retest sessions of three verbal declarative memory tasks: a Prose Stories Recall task, a Word Pair Associates task, and Rey Auditory Verbal Learning Test. Results showed that the nap group performed better than the no-nap group on both the Prose Stories Recall task and the Word Pair Associates task, but not on list learning. Our findings suggest that napping is beneficial to verbal declarative memory in adolescents, providing ecologically-valid empirical support for the sleep-dependent memory consolidation hypothesis using a napping paradigm in participants' naturalistic habitat. Our results demonstrate the potential importance of napping as a practical mnemonic intervention/compensatory strategy for student populations.

Effect of a Cooling Kit on Physiology and Performance Following Exercise in the Heat.

CONTEXT: Exercising in the heat leads to an increase in body temperature that can increase the risk of heat illness or cause detriments in exercise performance. OBJECTIVE: To examine a phase change heat emergency kit (HEK) on thermoregulatory and perceptual responses and subsequent exercise performance following exercise in the heat. DESIGN: Two randomized crossover trials that consisted of 30 minutes of exercise, 15 minutes of treatment (T1), performance testing (5-10-5 pro-agility test and 1500-m run), and another 15 minutes of treatment (T2) identical to T1. SETTING: Outdoors in the heat (wet-bulb globe temperature: 31.5°C [1.8°C] and relative humidity: 59.0% [5.6%]). PARTICIPANTS: Twenty-six (13 men and 13 women) individuals (aged 20-27 y). INTERVENTIONS: Treatment was performed with HEK and without HEK (control, CON) modality. MAIN OUTCOME MEASURES: Gastrointestinal temperature, mean skin temperature, thirst sensation, and muscle pain. RESULTS: Maximum gastrointestinal temperature following exercise and performance was not different between trials (P > .05). Cooling rate was faster during T1 CON (0.053°C/min [0.049°C/min]) compared with HEK (0.043°C/min [0.032°C/min]; P = .01). Mean skin temperature was lower in HEK during T1 (P < .001) and T2 (P = .05). T2 thirst was lower in CON (P = .02). Muscle pain was lower in HEK in T2 (P = .03). Performance was not altered (P > .05). CONCLUSIONS: HEK improved perception but did not enhance cooling or performance following exercise in the heat. HEK is therefore not recommended to facilitate recovery, treat hyperthermia, or improve performance.

Effect of hypohydration on postsynaptic cutaneous vasodilation and sweating in healthy men.

Hypohydration decreases cutaneous vasodilation and sweating during heat stress, but it is unknown if these decrements are from postsynaptic (i.e., sweat gland/blood vessel) alterations. The purpose of this study was to determine if hypohydration affects postsynaptic cutaneous vasodilation and sweating responses. Twelve healthy men participated in euhydrated (EU) and hypohydrated (HY) trials, with hypohydration induced via fluid restriction and passive heat stress. Changes in cutaneous vascular conductance (CVC; %max) in response to incremental intradermal infusion of the endothelium-independent vasodilator sodium nitroprusside (SNP) and the endothelium-dependent vasodilator methacholine chloride (MCh) were assessed by laser Doppler flowmetry. Local sweat rate (LSR) was simultaneously assessed at the MCh site via ventilated capsule. At the end of the last dose, maximal CVC was elicited by delivering a maximal dose of SNP (5 × 10-2 M) for 30 min to both sites with simultaneous local heating (~44°C) at the SNP site. The concentration of drug needed to elicit 50% of the maximal response (log EC50) was compared between hydration conditions. The percent body mass loss was greater with HY vs. EU (-2.2 ± 0.7 vs. -0.1 ± 0.7%, P < 0.001). Log EC50 of endothelium-dependent CVC was lower with EU (-3.62 ± 0.22) vs. HY (-2.93 ± 0.08; P = 0.044). Hypohydration did not significantly alter endothelium-independent CVC or LSR (both P > 0.05). In conclusion, hypohydration attenuated endothelium-dependent CVC but did not affect endothelium-independent CVC or LSR responses. These data suggest that reductions in skin blood flow accompanying hypohydration can be partially attributed to altered postsynaptic function.

Effect of passive heat stress and exercise in the heat on arterial stiffness.

PURPOSE: Prior evidence indicates that acute heat stress and aerobic exercise independently reduce arterial stiffness. The combined effects of exercise and heat stress on PWV are unknown. The purpose of this study was to determine the effects of heat stress with passive heating and exercise in the heat on arterial stiffness. METHODS: Nine participants (n = 3 females, 47 ± 11 years old; 24.1 ± 2.8 kg/m2) completed four trials. In a control trial, participants rested supine (CON). In a passive heating trial (PH), participants were heated with a water-perfusion suit. In two other trials, participants cycled at ~50% of [Formula: see text] in a hot (~40 °C; HC trial) or cool (~15 °C; CC trial) environment. Arterial stiffness, measured by PWV, was obtained at baseline and after each intervention (immediately, 15, 30, 45, and 60 min post). Central PWV (C PWV) was assessed between the carotid/femoral artery sites. Upper and lower peripheral PWV was assessed using the radial/carotid (U PWV) and dorsalis pedis/femoral (L PWV) artery sites. The mean body temperature (T B) was calculated from the skin and rectal temperatures. RESULTS: No significant changes in T B were observed during the CON and CC trials. As expected, the PH and HC trials elevated T B 2.69 ± 0.23 °C and 1.67 ± 0.27 °C, respectively (p < 0.01). PWV did not change in CON, CC, or HC (p > 0.05). However, in the PH trial, U PWV was reduced immediately (-107 ± 81 cm/s) and 15 min (-93 ± 82 cm/s) post-heating (p < 0.05). CONCLUSIONS: Heat stress via exercise in the heat does not acutely change arterial stiffness. However, passive heating reduces U PWV, indicating that heat stress has an independent effect on PWV.

Effect of Caffeine on Perceived Soreness and Functionality Following an Endurance Cycling Event.

Caldwell, AR, Tucker, MA, Butts, CL, McDermott, BP, Vingren, JL, Kunces, LJ, Lee, EC, Munoz, CX, Williamson, KH, Armstrong, LE, and Ganio, MS. Effect of caffeine on perceived soreness and functionality following an endurance cycling event. J Strength Cond Res 31(3): 638-643, 2017-Caffeine can reduce muscle pain during exercise; however, the efficacy of caffeine in improving muscle soreness and recovery from a demanding long-duration exercise bout has not been established. The purpose of this study was to investigate the effects of caffeine intake on ratings of perceived muscle soreness (RPMS) and perceived lower extremity functionality (LEF) following the completion of a 164-km endurance cycling event. Before and after cycling RPMS (1-to-6; 6 = severe soreness) and LEF (0-to-80; 80 = full functionality) were assessed by questionnaires. Subjects ingested 3 mg/kg body mass of caffeine or placebo pills in a randomized, double-blind fashion immediately after the ride and for the next 4 mornings (i.e., ∼800 hours) and 3 afternoons (i.e., ∼1200 hours). Before each ingestion, RPMS and LEF were assessed. Afternoon ratings of LEF were greater with caffeine ingestion the first day postride (65.0 ± 6.1 vs. 72.3 ± 6.7; for placebo and caffeine, respectively; p = 0.04), but at no other time points (p > 0.05). The caffeine group tended to have lower overall RPMS in the afternoon versus placebo (i.e., main effect of group; 1.1 ± 0.2 vs. 0.5 ± 0.2; p = 0.09). Afternoon RPMS for the legs was significantly lower in the caffeine group (main effect of caffeine; 1.3 ± 0.2 vs. 0.5 ± 0.3; p = 0.05). In conclusion, ingesting caffeine improved RPMS for the legs, but not LEF in the days following an endurance cycling event. Athletes may benefit from ingesting caffeine in the days following an arduous exercise bout to relieve feelings of soreness and reduced functionality.

No Change in 24-Hour Hydration Status Following a Moderate Increase in Fluid Consumption.

PURPOSE: To investigate changes in 24-hour hydration status when increasing fluid intake. METHODS: Thirty-five healthy males (age 23.8 ± 4.7 years; mass 74.0 ± 9.4 kg) were divided into 4 treatment groups for 2 weeks of testing. Volumes of 24-hour fluid ingestion (including water from food) for weeks 1 and 2 was 35 and 40 ml/kg body mass, respectively. Each treatment group was given the same proportion of beverages in each week of testing: water only (n = 10), water + caloric cola (n = 7), water + noncaloric cola (n = 10), or water + caloric cola + noncaloric cola + orange juice (n = 8). Serum osmolality (Sosm), total body water (TBW) via bioelectrical impedance, 24-hour urine osmolality (Uosm), and volume (Uvol) were analyzed at the end of each 24-hour intervention. RESULTS: Independent of treatment, total beverage consumption increased 22% from week 1 to 2 (1685 ± 320 to 2054 ± 363 ml; p < 0.001). Independent of beverage assignment, the increase in fluid consumption between weeks 1 and 2 did not change TBW (43.4 ± 5.2 vs 43.0 ± 4.8 kg), Sosm (292 ± 5 vs 292 ± 5 mOsm/kg), 24-hour Uosm (600 ± 224 vs 571 ± 212 mOsm/kg), or 24-hour Uvol (1569 ± 607 vs 1580 ± 554 ml; all p > 0.05). CONCLUSIONS: Regardless of fluid volume or beverage type consumed, measures of 24-hour hydration status did not differ, suggesting that standard measures of hydration status are not sensitive enough to detect a 22% increase in beverage consumption.

Effects of mild hypohydration on cooling during cold-water immersion following exertional hyperthermia.

PURPOSE: We investigated the effects of mild hypohydration compared to euhydration on the cooling efficacy of cold-water immersion (CWI). METHODS: Fourteen participants (eight male, six female; age 26 ± 5 years; ht 1.77 ± 0.08 m; wt 72.2 ± 8.8 kg; 20.6 ± 7.4 % body fat) completed one euhydrated (EU) trial followed by one hypohydrated trial (HY; via 24 h fluid restriction) in an environmental chamber (33.6 ± 0.9 °C, 55.8 ± 1.7 % RH). Volitional exercise was performed in a manner that matched end-exercise rectal temperature (T re) through repeating exercise mode and intensity. Participants were then immersed in ice water (2.0 ± 0.8 °C) until T re reached 38.1 °C or for a maximum of 15 min. T re, heart rate (HR), skin blood flux (SBF) and mean skin temperature (T sk) were monitored continuously during cooling. RESULTS: Pre-cooling body mass was decreased in the HY trial (-2.66 ± 1.23 % body mass) and maintained in the EU trial (-0.66 ± 0.44 %) compared to baseline mass (P < 0.001). Cooling rates were faster when EU (0.14 ± 0.05 °C/min) compared to HY (0.11 ± 0.05 °C/min, P = 0.046). HR, SBF, and T sk were not different between EU and HY trials (P > 0.05), however, all variables significantly decreased with immersion independent of hydration status (P < 0.001). CONCLUSION: The primary finding was that hypohydration modestly attenuates the rate of cooling in exertionally hyperthermic individuals. Regardless of hydration status, the cooling efficacy of CWI was preserved and should continue to be utilized in the treatment of exertional hyperthermia.

Forearm cutaneous vascular and sudomotor responses to whole body passive heat stress in young smokers.

The purpose of this study was to compare smokers and nonsmokers' sudomotor and cutaneous vascular responses to whole body passive heat stress. Nine regularly smoking (SMK: 29 ± 9 yr; 10 ± 6 cigarettes/day) and 13 nonsmoking (N-SMK: 27 ± 8 yr) males were passively heated until core temperature (TC) increased 1.5°C from baseline. Forearm local sweat rate (LSR) via ventilated capsule, sweat gland activation (SGA), sweat gland output (SGO), and cutaneous vasomotor activity via laser-Doppler flowmetry (CVC) were measured as mean body temperature increased (ΔTb) during passive heating using a water-perfused suit. Compared with N-SMK, SMK had a smaller ΔTb at the onset of sweating (0.52 ± 0.19 vs. 0.35 ± 0.14°C, respectively; P = 0.03) and cutaneous vasodilation (0.61 ± 0.21 vs. 0.31 ± 0.12°C, respectively; P < 0.01). Increases in LSR and CVC per °C ΔTb (i.e., sensitivity) were similar in N-SMK and SMK (LSR: 0.63 ± 0.21 vs. 0.60 ± 0.40 Δmg/cm(2)/min/°C ΔTb, respectively, P = 0.81; CVC: 82.5 ± 46.2 vs. 58.9 ± 23.3 Δ%max/°C ΔTb, respectively; P = 0.19). However, the plateau in LSR during whole body heating was higher in N-SMK vs. SMK (1.00 ± 0.13 vs. 0.79 ± 0.26 mg·cm(-2)·min(-1); P = 0.03), which was likely a result of higher SGO (8.94 ± 3.99 vs. 5.94 ± 3.49 µg·gland(-1)·min(-1), respectively; P = 0.08) and not number of SGA (104 ± 7 vs. 121 ± 9 glands/cm(2), respectively; P = 0.58). During whole body passive heat stress, smokers had an earlier onset for forearm sweating and cutaneous vasodilation, but a lower local sweat rate that was likely due to lower sweat output per gland. These data provide insight into local (i.e., forearm) thermoregulatory responses of young smokers during uncompensatory whole body passive heat stress.

REM sleep enhancement of probabilistic classification learning is sensitive to subsequent interference.

During wakefulness the brain creates meaningful relationships between disparate stimuli in ways that escape conscious awareness. Processes active during sleep can strengthen these relationships, leading to more adaptive use of those stimuli when encountered during subsequent wake. Performance on the Weather Prediction Task (WPT), a well-studied measure of implicit probabilistic learning, has been shown to improve significantly following a night of sleep, with stronger initial learning predicting more nocturnal REM sleep. We investigated this relationship further, studying the effect on WPT performance of a daytime nap containing REM sleep. We also added an interference condition after the nap/wake period as an additional probe of memory strength. Our results show that a nap significantly boosts WPT performance, and that this improvement is correlated with the amount of REM sleep obtained during the nap. When interference training is introduced following the nap, however, this REM-sleep benefit vanishes. In contrast, following an equal period of wake, performance is both unchanged from training and unaffected by interference training. Thus, while the true probabilistic relationships between WPT stimuli are strengthened by sleep, these changes are selectively susceptible to the destructive effects of retroactive interference, at least in the short term.

Hydration Status over 24-H Is Not Affected by Ingested Beverage Composition.

OBJECTIVE: To investigate the 24-h hydration status of healthy, free-living, adult males when given various combinations of different beverage types. METHODS: Thirty-four healthy adult males participated in a randomized, repeated-measures design in which they consumed: water only (treatment A), water+cola (treatment B), water+diet cola (treatment C), or water+cola+diet cola+orange juice (treatment D) over a sedentary 24-h period across four weeks of testing. Volumes of fluid were split evenly between beverages within each treatment, and when accounting for food moisture content and metabolic water production, total fluid intake from all sources was equal to 35 ± 1 ml/kg body mass. Urine was collected over the 24-h intervention period and analyzed for osmolality (Uosm), volume (Uvol) and specific gravity (USG). Serum osmolality (Sosm) and total body water (TBW) via bioelectrical impedance were measured after the 24-h intervention. RESULTS: 24-h hydration status was not different between treatments A, B, C, and D when assessed via Uosm (590 ± 179; 616 ± 242; 559 ± 196; 633 ± 222 mOsm/kg, respectively) and Uvol (1549 ± 594; 1443 ± 576; 1690 ± 668; 1440 ± 566 ml) (all p > 0.05). A -difference in 24-h USG was observed between treatments A vs. D (1.016 ± 0.005 vs. 1.018 ± 0.007; p = 0.049). There were no differences between treatments at the end of the 24-h with regard to Sosm (291 ± 4; 293 ± 5; 292 ± 5; 293 ± 5 mOsm/kg, respectively) and TBW (43.9 ± 5.9; 43.8 ± 6.0; 43.7 ± 6.1; 43.8 ± 6.0 kg) (all p > 0.05). CONCLUSIONS: Regardless of the beverage combination consumed, there were no differences in providing adequate hydration over a 24-h period in free-living, healthy adult males. This confirms that beverages of varying composition are equally effective in hydrating the body.

The effect of caffeine on maximal oxygen uptake and vertical jump performance in male basketball players.

This study investigated whether performance enhancement from caffeine described by other researchers transfers to male basketball players. The effects of caffeine ingestion were studied in a maximal-effort test on a treadmill that was followed by a vertical-jump test. Five elite-level male basketball players completed a graded treadmill test that measured maximal oxygen uptake, blood lactate profiles, respiratory exchange ratio, and rating of perceived exertion at each 3-minute stage. After a 15-minute warm-down, the subjects performed 10 vertical rebound jumps. Each subject completed the test twice--once with a 3 mg·kg(-1) of body weight dose of caffeine and once with a placebo, with the dosage administered 60 minutes before commencement of exercise. The test was thus administered according to a double-blind protocol. No substantial trends were found between caffeine and control trials, regardless of trial order. The study showed that the specified dosage had negligible effects on the players' power and endurance performance and had no efficacy as an ergogenic aid for male basketball players.

Endothelin receptor blockade blunts the pressor response to acute stress in men and women with obesity.

Obesity is associated with dysregulation of the endothelin system. In individuals with obesity, an exaggerated pressor response to acute stress is accompanied by increased circulating endothelin-1 (ET-1). The impact of combined endothelin A/B receptor (ETA/B) antagonism on the stress-induced pressor response in overweight/obese (OB) individuals is unknown. The objective of this study is to test the hypothesis that treatment with an ETA/B antagonist (bosentan) would reduce the stress-induced pressor response and arterial stiffness in overweight/obese compared with normal weight (NW) individuals. Forty participants [normal weight (NW): n = 20, body mass index (BMI): 21.7 ± 2.4 kg/m2 and overweight/obese (OB): n = 20, BMI: 33.8 ± 8.2 kg/m2] were randomized to placebo or 125 mg of bosentan twice a day (250 mg total) for 3 days. Hemodynamics were assessed before, during, and after a cold pressor test (CPT). Endothelin-1 was assessed at baseline and immediately after CPT. Following a washout period, the same protocol was repeated with the opposite treatment. The change from baseline in mean arterial pressure (MAP) during CPT following bosentan was significantly lower (P = 0.039) in the OB group than in the NW group (OB: 28 ± 12 vs. NW: 34 ± 15 mmHg). These results suggest that ETA/B antagonism favorably blunts the pressor response to acute stress in overweight/obese individuals.NEW & NOTEWORTHY Findings from our current translational investigation demonstrate that dual endothelin A/B receptor antagonism blunts the pressor response to acute stress in overweight/obese individuals. These results suggest that modulation of the endothelin system may represent a novel therapeutic target to reduce cardiovascular disease (CVD) risk by blunting the stress response in overweight/obese individuals.