The application of heating film to hands reduces the decline in manual dexterity performance associated with cold exposure.

PURPOSE: Exposure to cold temperatures decreases finger temperature (Tfing) and dexterity. Decreased manual function and dexterity can be serious safety risks, especially in tasks that require fine motor movements that must be performed outdoors. The aim of this study was to determine whether hand heating with a minimal power requirement (14.8 W) results in a smaller reduction in Tfing and manual dexterity performance during mild cold exposure compared to a non-heated control condition. METHODS: In a randomized crossover design, twenty-two healthy participants were exposed to a moderately cold environment (5  ºC) for 90 min. One condition had no intervention (CON), while the other had the palmar and dorsal hands heated (HEAT) by using electric heating films. Tfing and cutaneous vascular conductance (CVC) were continuously monitored using laser Doppler flowmetry. Manual dexterity performance and cognitive function were assessed by the Grooved Pegboard Test (GPT) and Stroop Color-Word (SCW) test, respectively, during the baseline period and every 30 min during the cold exposure. RESULTS: After the cold exposure, Tfing was higher in HEAT relative to CON (CON 9.8 vs. HEAT 13.7 ºC, p < 0.0001). GPT placing time, as an index of dexterity performance, was also shorter in HEAT by 14.5% (CON 69.10 ± 13.08 vs. HEAT 59.06 ± 7.99 s, p < 0.0001). There was no difference in CVC between the two conditions during the cold exposure (p > 0.05 for all). Cognitive function was similar between two conditions (p > 0.05 for all). CONCLUSION: The proposed hand heating method offers a practical means of heating fingers to maintain dexterity throughout prolonged cold exposure.

Effect of 4-week intermittent hypoxic exercise training for repeated vertical jump performance in untrained males.

BACKGROUND: To be successful in sports, it is critical to maintain a high level of muscular power throughout a game. Physiological adaptations induced by hypoxic exercise training would provide benefits for fatigue-resisting ability during repeated explosive exercise. The aim of this study was to determine whether a 4-week intermittent hypoxic exercise training program is more effective in improving power endurance during repeated vertical jumps (VJs) when compared with a normoxic counterpart. METHODS: Eighteen young adult males were divided into two training groups: 1) normoxic training group (NT, FiO2: 20.9%, N.=9); and 2) hypoxic training group (HT, FiO2: 13.7%, N.=9). For both NT and HT, participants performed three sessions per week for four weeks. Each session consisted of a 60-min exercise session including strength and power training. A repeated VJ (40 reps/set, 2 sets with 5 min rest given between them) was performed before and after the training (pretraining and post-training). RESULTS: The HT group displayed an improvement in repeated VJ performance in a later phase of set 1 following the training (25-30 rep: pretraining 26.49±6.20 vs. post-training 30.55±5.37cm, P=0.0285; 30-35 rep: pretraining 25.08±5.29 vs. post-training 29.56±5.37cm, P=0.0064; 35-40 rep: pretraining 25.05±5.51 vs. post-training 29.28±5.71cm, P=0.0161). In set 2, repeated VJ performance in the later phase was also enhanced in HT following the training (P<0.05 for all). No changes in repeated VJ performance were seen in NT following the training (P>0.05 for all). Also, the HT group showed a trend towards a decrease in Fatigue Index in set 1 (pretraining 23.51±13.27 vs. Post 11.87±12.51%, P=0.1308) and set 2 (pretraining 29.11±13.66 vs. post-training 17.81±17.97%, P=0.1588) following the training. CONCLUSIONS: Hypoxic exercise training can be an effective training modality to improve fatigue-resisting ability during repeated explosive exercise.

Effects of cutaneous administration of an over-the-counter menthol cream during temperate-water immersion for exercise-induced hyperthermia in men.

Introduction: Hyperthermia impairs various physiological functions and physical performance. We examined the effects of cutaneous administration with an over-the-counter (OTC) analgesic cream containing 20% methyl salicylate and 6% L-menthol during temperate-water immersion (TWI) for exercise-induced hyperthermia. Methods: In a randomized crossover design, twelve healthy males participated in both of two experiments. Firstly, participants underwent a 15-min TWI at 20°C with (CREAM) or without (CON) cutaneous application of an analgesic cream. Cutaneous vascular conductance (CVC) was measured using laser doppler flowmetry during TWI. In a subsequent experiment, same participants performed a 30-min strenuous interval exercise in a heated (35°C) environment to induce hyperthermia (~39°C), which was followed by 15 min of TWI. Results: Core body temperature, as measured by an ingestible telemetry sensor, and mean arterial pressure (MAP) were measured. CVC and %CVC (% baseline) were higher during TWI in CREAM than in CON (Condition effect: p = 0.0053 and p = 0.0010). An additional experiment revealed that core body heat loss during TWI was greater in CREAM than in CON (Cooling rate: CON 0.070 ± 0.020 vs. CREAM 0.084°C ± 0.026°C/min, p = 0.0039). A more attenuated MAP response was observed during TWI in CREAM than in CON (Condition effect: p = 0.0007). Conclusion: An OTC analgesic cream containing L-menthol and MS augmented cooling effects when cutaneously applied during TWI in exercise-induced hyperthermia. This was, at least in part, due to the counteractive vasodilatory effect of the analgesic cream. The cutaneous application of OTC analgesic cream may therefore provide a safe, accessible, and affordable means of enhancing the cooling effects of TWI.

Application of blood flow restriction in hypoxic environment augments muscle deoxygenation without compromising repeated sprint exercise performance.

NEW FINDINGS: What is the central question of this study? Does applying blood flow restriction during the rest periods of repeated sprint exercise in a hypoxic environment lead to greater local hypoxia within exercising muscles without compromising training workload? What is the main finding and its importance? Repeated sprint exercise with blood flow restriction administered during rest periods under systemic hypoxia led to severe local hypoxia within the exercised muscles without a reduction in power output. The maintained power output might be due to elevated neuromuscular activation. Accordingly, the proposed repeated sprint exercise in the current study may be an effective training modality. ABSTRACT: Repeated sprint exercise (RSE) is a popular training modality for a wide variety of athletic activities. The purpose of this study was to assess the combined effects of systemic hypoxia and blood flow restriction (BFR) on muscle deoxygenation and RSE performance. Twelve healthy young men performed a standard RSE training modality (five sets of 10 s maximal sprint with a 60 s rest) under four different conditions: (1) normoxic control (NC), normoxia (N, 20.9%) + control BFR (C, 0 mmHg); (2) normoxic BFR (NB), normoxia (N, 20.9%) + BFR (B, 140 mmHg); (3) hypoxic control (HC), hypoxia (H, 13.7%) + control BFR (C, 0 mmHg); and (4) hypoxic BFR (HB): hypoxia (H, 13.7%) + BFR (B, 140 mmHg). BFR was only administered during the rest period of the respective RSE trials. In the local exercising muscles, muscle oxygen saturation ( Sm O 2 $\textit{Sm}{O}_{2}$ ) and neuromuscular activity were measured using near-infrared spectroscopy and surface electromyography, respectively. SmO2 was lower in systemic hypoxia conditions relative to normoxia conditions (P < 0.05). A rther decrease in SmO2 was observed in HB relative to HC (Set 1: HC 70.0 ± 17.5 vs. HB 57.4 ± 11.3%, P = 0.001; Set 4: HC 67.5 ± 14.6 vs. HB 57.0 ± 12.0%, P = 0.013; Set 5: HC 61.0 ± 15.3 vs. HB 47.7 ± 11.9%, P < 0.001). No differences in RSE performance were observed between any of the conditions (P > 0.05). Interestingly, an elevated neuromuscular activity was seen in response to the BFR, particularly during conditions of systemic hypoxia (P < 0.05). Thus, RSE with BFR administered during rest periods under systemic hypoxia led to severe local hypoxia without compromising training workload.

Topical Analgesic Containing Methyl Salicylate and L-Menthol Accelerates Heat Loss During Skin Cooling for Exercise-Induced Hyperthermia.

Hyperthermia impairs physical performance and, when prolonged, results in heat stroke or other illnesses. While extensive research has investigated the effectiveness of various cooling strategies, including cold water immersion and ice-suit, there has been little work focused on overcoming the cutaneous vasoconstriction response to external cold stimulation, which can reduce the effectiveness of these treatments. Over-the-counter (OTC) topical analgesics have been utilized for the treatment of muscle pain for decades; however, to date no research has examined the possibility of taking advantage of their vasodilatory functions in the context of skin cooling. We tested whether an OTC analgesic cream containing 20% methyl salicylate and 6% L-menthol, known cutaneous vasodilators, applied to the skin during skin cooling accelerates heat loss in exercise-induced hyperthermia. Firstly, we found that cutaneous application of OTC topical analgesic cream can attenuate cold-induced vasoconstriction and enhance heat loss during local skin cooling. We also revealed that core body heat loss, as measured by an ingestible telemetry sensor, could be accelerated by cutaneous application of analgesic cream during ice-suit cooling in exercise-induced hyperthermia. A blunted blood pressure response was observed during cooling with the analgesic cream application. Given the safety profile and affordability of topical cutaneous analgesics containing vasodilatory agents, our results suggest that they can be an effective and practical tool for enhancing the cooling effects of skin cooling for hyperthermia.

The Relationship between Different Amounts of Physical Exercise, Internal Inhibition, and Drug Craving in Individuals with Substance-Use Disorders.

PURPOSE: To explore the relationship between different amounts of physical exercise and drug craving in individuals with substance-use disorders (SUD), and to reveal the mediating role of internal inhibition between physical activity and drug craving. METHOD: This study adopted the Physical Activity Rating Scale, Internal Inhibition Scale, and Drug Craving Scale to assess 438 cases of SUD in a compulsory isolation detoxification center in southwest China. RESULTS: (1) The amount of physical exercise individuals with SUD engaged in was positively correlated with internal inhibition and negatively correlated with drug craving, while the amount of physical exercise was negatively correlated with drug craving. (2) The amount of physical exercise was able to negatively predict drug craving in addicts, the amount of physical exercise and internal inhibition were able to jointly predict drug craving, and internal inhibition played a mediating role between the amount of physical exercise and drug craving (the mediating effect was 0.22). (3) There was a dose-effect relationship regarding different amounts of physical exercises and drug craving. Internal inhibition did not mediate between a low amount of physical exercise and drug craving, it played a partial mediating role between a moderate amount of physical exercise and drug craving (the mediating effect was -0.19), and it played a partial mediating role between a high amount of physical exercise and drug craving (the mediating effect was -0.15). CONCLUSIONS: Physical activity has a positive effect on reducing drug craving in individuals with SUD. Moreover, in the process of sports rehabilitation for SUD, medium or high amounts of physical activity were required in order to effectively reduce and alleviate drug cravings.

Acute Local Cooling to the Lower Body during Recovery Does Not Improve Repeated Vertical Jump Performance.

BACKGROUND: Local cooling, or cryotherapy, has received attention due to its effects on athlete recovery before or after strenuous exercise. This study seeks to verify the effectiveness of 3 min applications of acute local cooling to the lower extremities between sets of a repeated vertical jump exercise. METHODS: Using a randomized crossover design, twelve subjects performed a total of 3 sets of 30 consecutive maximal vertical jumps and were allowed a recovery period of 5 min after each set. In the recovery period, subjects rested with or without a cooling suit worn on their lower legs. Changes in heart rate, blood lactate, and rate of perceived exertion were assessed. RESULTS: Vertical jump performance steadily decreased during 30 consecutive vertical jumps in all 3 sets; however, no differences in jump performance were observed among the groups. Heart rate, blood lactate, and rate of perceived exertion tended to be lower in the cooling recovery group relative to the control group. CONCLUSION: The current study provides evidence that acute local cooling recovery after a vertical jump exercise may not add any performance benefits but may provide a psychological benefit. The effectiveness of acute local cooling in other functional performances should be addressed in further research.

Effects of Elastic Band Exercise on Functional Fitness and Blood Pressure Response in the Healthy Elderly.

Purpose: This study investigated the effects of 12 weeks of moderate intensity elastic band exercise (EBE) on functional fitness and blood pressure parameters in the elderly. Methods: 27 healthy older adults were randomly assigned to an exercise group (n = 15, age: 75.1 ± 1.4 years) and a control group (n = 12, age: 72.3 ± 1.4 years). Participants performed EBE for 60 min, three times a week, over the course of three months. The EBE consisted of incremental resistance and aerobic exercises designed to improve whole body fitness. Functional fitness and resting cardiovascular parameters were assessed before and after the exercise training program. Results: Grip strength, sit and reach, and one-leg stance improved significantly in the exercise group, while no significant improvements were found in chair stand and timed up and go (p < 0.05). Cardiovascular parameters including systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse pressure significantly decreased in the exercise group relative to the control group (p < 0.05). Conclusions: Findings of the present study suggest that safe, inexpensive, and easily accessible EBE program with circuit training components play a significant role in improving upper and lower body fitness, as well as cardiovascular fitness, in the elderly.

Effects of acute cooling on cycling anaerobic exercise performance and neuromuscular activity: a randomized crossover study.

BACKGROUND: While cryotherapy is known for its favorable long-term recovery effects on muscle-damaging eccentric and plyometric exercises, studies showed that cryotherapy when used as an acute recovery mode (same day) had a negligible or negative effect on high-intensity and explosive exercises. However, there is lack of evidence regarding the mechanisms underlying the detrimental effect of acute cooling on the anaerobic performance. We hypothesized that acute cooling for the lower body would reduce anaerobic power output during a subsequent Wingate anaerobic tests (WAnT), which is at least in part due to decreased neuromuscular firing rate as indexed by mean frequency. METHODS: We performed a randomized crossover design experiment. Eleven young healthy males completed two consecutive 30-sec Wingate anaerobic tests (WAnT 1 and 2). Subjects rested for 10 min between the WAnT 1 and the WAnT 2. Neuromuscular activity on the rectus femoris of both legs was recorded using wireless electromyography (EMG) during WAnT. RESULTS: Anaerobic power during the first 5 sec of WAnT 2 was decreased in the cooling suit recovery group relative to WAnT 1. Mean frequency (MNF) in WAnT 2 was also lower in a cooled leg during WAnT 2 during the first 10 sec when compared with WAnT 1. CONCLUSIONS: Acute cooling application blunts the initial phase of anaerobic power output during a subsequent WAnT, which could be explained by a concomitant reduction in neuromuscular firing rate. Given that cryotherapy is widely utilized in a variety of sports, athletes and trainers should pay close attention to the appropriate application of cryotherapy.

Liver sympathetic denervation reverses obesity-induced hepatic steatosis.

KEY POINTS: Non-alcoholic fatty liver disease, characterized in part by elevated liver triglycerides (i.e. hepatic steatosis), is a growing health problem. In this study, we found that hepatic steatosis is associated with robust hepatic sympathetic overactivity. Removal of hepatic sympathetic nerves reduced obesity-induced hepatic steatosis. Liver sympathetic innervation modulated hepatic lipid acquisition pathways during obesity. ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) affects 1 in 3 Americans and is a significant risk factor for type II diabetes mellitus, insulin resistance and hepatic carcinoma. Characterized in part by excessive hepatic triglyceride accumulation (i.e. hepatic steatosis), the incidence of NAFLD is increasing - in line with the growing obesity epidemic. The role of the autonomic nervous system in NAFLD remains unclear. Here, we show that chronic hepatic sympathetic overactivity mediates hepatic steatosis. Direct multiunit recordings of hepatic sympathetic nerve activity were obtained in high fat diet and normal chow fed male C57BL/6J mice. To reduce hepatic sympathetic nerve activity we utilized two approaches including pharmacological ablation of the sympathetic nerves and phenol-based hepatic sympathetic nerve denervation. Diet-induced NAFLD was associated with a nearly doubled firing rate of the hepatic sympathetic nerves, which was largely due to an increase in efferent nerve traffic. Furthermore, established high fat diet-induced hepatic steatosis was effectively reduced with pharmacological or phenol-based removal of the hepatic sympathetic nerves, independent of changes in body weight, caloric intake or adiposity. Ablation of liver sympathetic nerves was also associated with improvements in liver triglyceride accumulation pathways including free fatty acid uptake and de novo lipogenesis. These findings highlight an unrecognized pathogenic link between liver sympathetic outflow and hepatic steatosis and suggest that manipulation of the liver sympathetic nerves may represent a novel therapeutic strategy for NAFLD.

Attenuated cutaneous microvascular function in healthy young African Americans: Role of intradermal l-arginine supplementation.

It has been established that endothelial function in conduit vessels is reduced in young African Americans (AA) relative to Caucasian Americans (CA). However, less is known regarding endothelial function in microvasculature of young AA. We hypothesized that microvascular function in response to local heating of skin is attenuated in young AA relative to age-matched CA due largely to the lack of NO bioavailability, which is in turn improved by intradermal l-arginine supplementation and/or inhibition of arginase. Nine AA and nine CA adults participated in this study. Participants were instrumented with four microdialysis membranes in the cutaneous vasculature of one forearm and were randomly assigned to receive 1) lactated Ringer's solution as a control site; 2) 20 mM NG-nitro-l-arginine (l-NAME) to inhibit NO synthase activity; 3) 10 mM l-arginine to local supplement l-arginine; or 4) a combination of 5.0 mM (S)-(2­boronoethyl)-l-cysteine-HCL (BEC) and 5.0 mM Nω-hydroxy-nor-l-arginine (nor-NOHA) at a rate of 2.0 µl/min to locally inhibit arginase activity. Cutaneous vascular conductance (CVC) was calculated as red blood cell flux divided by mean arterial pressure. All CVC data were presented as a percentage of maximal CVC (%CVCmax) that was determined by maximal cutaneous vasodilation induced by 44 °C heating plus sodium nitroprusside administration. The response during the 42 °C local heating plateau was blunted in the AA at the control site (CA: 84 ±â€¯12 vs. AA: 62 ±â€¯6 vs. %CVCmax; P < 0.001). This response was improved in AA at the l-arginine site (Control: 62 ±â€¯6 vs. l-arginine: 70 ±â€¯18%CVCmax; P < 0.05) but not in the arginase inhibited site (Control: 62 ±â€¯6 vs. Arginase inhibited: 62 ±â€¯13%CVCmax; P = 0.91). In addition, the AA group had an attenuated NO contribution to the plateau phase during 42 °C local heating relative to the CA group (CA: 56 ±â€¯14 vs. AA: 44 ±â€¯6 Δ %CVCmax; P < 0.001). These findings suggest that 1) cutaneous microvascular function in response to local heating is blunted in young AA when compared to age-matched young CA; 2) this attenuated response is partly related to decrease in NO bioavailability in young AA; and 3) a local infusion of l-arginine, but not arginase inhibition, improves cutaneous microvascular responses to local heating in young AA relative to CA.

Tempol augments the blunted cutaneous microvascular thermal reactivity in healthy young African Americans.

NEW FINDINGS: What is the central question of this study? The purpose was to determine whether there is a difference between African Americans and Caucasians in cutaneous microvascular function and whether this difference is attributable to elevated oxidative stress. What is the main finding and its importance? The main finding is that African Americans have an attenuated cutaneous vasodilatation during local heating relative to Caucasians that is restored with local infusion of the superoxide dismutase mimetic, tempol. This suggests that superoxide mediates microvascular dysfunction and might contribute to the greater prevalence of cardiovascular disease in this population. ABSTRACT: African Americans (AA) have elevated risk for cardiovascular disease relative to other populations. We hypothesized that the cutaneous hyperaemic response to local heating is reduced in young AA relative to Caucasian Americans (CA) and that this is attributable to elevated oxidative stress. As such, ascorbic acid (a global antioxidant) and tempol (a superoxide dismutase mimetic) would improve this response in AA. Microdialysis fibres received lactated Ringer solution (control), 10 mm ascorbic acid or 10 µm 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempol) at a rate of 2.0 µl min-1 . Cutaneous vascular conductance (CVC) was calculated as the red blood cell flux divided by mean arterial pressure. Data were presented as a percentage of maximal CVC (%CVCmax ) induced by 44°C heating plus sodium nitroprusside. Twenty-four (12 AA, 12 CA) young (23 ± 4 years old) subjects participated. During 39°C heating, the %CVCmax was lower in AA at the control (CA, 65 ± 20% versus AA, 47 ± 15%; P < 0.05) and ascorbic acid sites (CA, 73 ± 14% versus AA: 49 ± 17%; P < 0.01). At the tempol site, there were no differences between groups. This was followed by infusion of 10 mm l-NAME at all sites to assess the contribution of nitric oxide to vasodilatation during local heating. The contribution of nitric oxide was lower in AA relative to CA at 39°C; however, this was restored with tempol. These data suggest that: (i) cutaneous vasodilatation in response to local heating is blunted in AA relative to CA; and (ii) elevated superoxide generation attenuates nitric oxide-mediated cutaneous vasodilatation in AA.

Blunted cerebral vascular responsiveness to hypercapnia in obese individuals.

NEW FINDINGS: What is the central question of this study? Is there a difference in the cerebral vascular response to rebreathing-induced hypercapnia between obese and lean individuals? What is the main finding and its importance? The main finding is that obese individuals have an attenuated increase in cerebral vascular conductance during hypercapnia relative to lean individuals. This finding suggests cerebral vascular dysfunction in this population, which might contribute to the greater prevalence of cerebral vascular and neurocognitive disease in this population. Obesity increases the risk of cardiovascular disease by >45%. Furthermore, obesity is a contributory factor to cognitive impairment and Alzheimer's disease. The mechanisms accounting for this increased disease risk have not been clarified. This study tested the hypothesis that the total range of change (a) in cerebral blood velocity (CBV) and cerebral vascular conductance (CVCI) and the maximal (y0) CBV and CVCI achieved during rebreathing-induced hypercapnia would be attenuated in obese individuals. Sixteen lean and 15 obese individuals participated. The magnitude of rebreathing-induced hypercapnia was similar between groups (lean, ∆15 ± 3 mmHg versus obese, ∆15 ± 2 mmHg; P = 0.82). The total range of change in CBV during rebreathing (a; expressed as a percentage) was similar between groups (lean, 91 ± 24% versus obese, 76 ± 19%, P = 0.07), whereas the total range of change in CVCI during rebreathing (a; expressed as a percentage) was attenuated in the obese individuals (lean, 71 ± 20% versus obese, 51 ± 15%, P < 0.01). Likewise, the maximal increase in CBV during rebreathing (y0; expressed as a percentage) was similar between groups (lean, 189 ± 22% versus obese, 179 ± 20%, P = 0.20), whereas the maximal increase in CVCI during rebreathing (y0; expressed as a percentage) was attenuated in the obese individuals (lean, 172 ± 19% versus obese, 155 ± 17 %, P = 0.01). These data indicate that the cerebral vascular response to rebreathing-induced hypercapnia is attenuated in obese individuals. This impairment might be a factor contributing to the elevated cerebral vascular and neurocognitive disease risk in this population.

Obesity-induced hepatic steatosis is mediated by endoplasmic reticulum stress in the subfornical organ of the brain.

Nonalcoholic fatty liver disease (NAFLD), characterized by an excess accumulation of hepatic triglycerides, is a growing health epidemic. While ER stress in the liver has been implicated in the development of NAFLD, the role of brain ER stress - which is emerging as a key contributor to a number of chronic diseases including obesity - in NAFLD remains unclear. These studies reveal that chemical induction of ER stress in the brain caused hepatomegaly and hepatic steatosis in mice. Conversely, pharmacological reductions in brain ER stress in diet-induced obese mice rescued NAFLD independent of body weight, food intake, and adiposity. Evaluation of brain regions involved revealed robust activation of ER stress biomarkers and ER ultrastructural abnormalities in the circumventricular subfornical organ (SFO), a nucleus situated outside of the blood-brain-barrier, in response to high-fat diet. Targeted reductions in SFO-ER stress in obese mice via SFO-specific supplementation of the ER chaperone 78-kDa glucose-regulated protein ameliorated hepatomegaly and hepatic steatosis without altering body weight, food intake, adiposity, or obesity-induced hypertension. Overall, these findings indicate a novel role for brain ER stress, notably within the SFO, in the pathogenesis of NAFLD.

Deletion of p22phox-dependent oxidative stress in the hypothalamus protects against obesity by modulating ß3-adrenergic mechanisms.

A role for oxidative stress in the brain has been suggested in the pathogenesis of diet-induced obesity (DIO), although the underlying neural regions and mechanisms remain incompletely defined. We tested the hypothesis that NADPH oxidase-dependent oxidative stress in the paraventricular nucleus (PVN), a hypothalamic energy homeostasis center, contributes to the development of DIO. Cre/LoxP technology was coupled with selective PVN adenoviral microinjection to ablate p22phox , the obligatory subunit for NADPH oxidase activity, in mice harboring a conditional p22phox allele. Selective deletion of p22phox in the PVN protected mice from high-fat DIO independent of changes in food intake or locomotor activity. This was accompanied by ß3-adrenoceptor-dependent increases in energy expenditure, elevations in brown adipose tissue thermogenesis, and browning of white adipose tissue. These data reveal a potentially novel role for brain oxidative stress in the development of DIO by modulating ß3-adrenoceptor mechanisms and point to the PVN as an underlying neural site.

A synthetic luciferin improves in vivo bioluminescence imaging of gene expression in cardiovascular brain regions.

Bioluminescence imaging is an effective tool for in vivo investigation of molecular processes. We have demonstrated the applicability of bioluminescence imaging to spatiotemporally monitor gene expression in cardioregulatory brain nuclei during the development of cardiovascular disease, via incorporation of firefly luciferase into living animals, combined with exogenous d-luciferin substrate administration. Nevertheless, d-luciferin uptake into the brain tissue is low, which decreases the sensitivity of bioluminescence detection, particularly when considering small changes in gene expression in tiny central areas. Here, we tested the hypothesis that a synthetic luciferin, cyclic alkylaminoluciferin (CycLuc1), would be superior to d-luciferin for in vivo bioluminescence imaging in cardiovascular brain regions. Male C57B1/6 mice underwent targeted delivery of an adenovirus encoding the luciferase gene downstream of the CMV promoter to the subfornical organ (SFO) or paraventricular nucleus of hypothalamus (PVN), two crucial cardioregulatory neural regions. While bioluminescent signals could be obtained following d-luciferin injection (150 mg/kg), CycLuc1 administration resulted in a three- to fourfold greater bioluminescent emission from the SFO and PVN, at 10- to 20-fold lower substrate concentrations (7.5-15 mg/kg). This CycLuc1-mediated enhancement in bioluminescent emission was evident early following substrate administration (i.e., 6-10 min) and persisted for up to 1 h. When the exposure time was reduced from 60 s to 1,500 ms, minimal signal in the PVN was detectable with d-luciferin, whereas bioluminescent images could be reliably captured with CycLuc1. These findings demonstrate that bioluminescent imaging with the synthetic luciferin CycLuc1 provides an improved physiological genomics tool to investigate molecular events in discrete cardioregulatory brain nuclei.

Neural Control of Non-vasomotor Organs in Hypertension.

Hypertension affects over 25 % of the population with the incidence continuing to rise, due in part to the growing obesity epidemic. Chronic elevations in sympathetic nerve activity (SNA) are a hallmark of the disease and contribute to elevations in blood pressure through influences on the vasculature, kidney, and heart (i.e., neurogenic hypertension). In this regard, a number of central nervous system mechanisms and neural pathways have emerged as crucial in chronically elevating SNA. However, it is important to consider that "sympathetic signatures" are present, with differential increases in SNA to regional organs that are dependent upon the disease progression. Here, we discuss recent findings on the central nervous system mechanisms and autonomic regulatory networks involved in neurogenic hypertension, in both non-obesity- and obesity-associated hypertension, with an emphasis on angiotensin-II, salt, oxidative and endoplasmic reticulum stress, inflammation, and the adipokine leptin.

Impaired endothelium independent vasodilation in the cutaneous microvasculature of young obese adults.

Microvascular dysfunction contributes to the development of cardiovascular and metabolic disease. This study tested the hypothesis that young obese (BMI>30 kg m(-2)), otherwise healthy, adults (N=15) have impaired microvascular function relative to age and sex matched, lean (BMI<25 kg m(-2)) individuals (N=14). Participants were instrumented with two microdialysis probes in the cutaneous vasculature of one forearm; one for a wide dose range of infusions of the endothelium-dependent vasodilator methacholine (MCh) and the other for the endothelium-independent vasodilator sodium nitroprusside (SNP). Local temperature at each site was clamped at 33 °C and cutaneous blood flow was indexed by laser Doppler flowmetry (LDF). LDF was recorded while 7 doses of each drug (MCh: 10(-6)-1M; SNP: 5 × 10(-8)-5 × 10(-2)M) were infused at a rate of 2 µl/min for 8 min per dose. Both sites finished with heating to 43 °C and 5 × 10(-2)M SNP to achieve site specific maximal vasodilation. Mean arterial blood pressure (MAP) was assessed in the last minute of each dose and was used for subsequent calculation of cutaneous vascular conductance (CVC; LDF/MAP) and responses were normalized to each individual site's maximal response (%CVCmax). Group four-parameter dose response curves were compared with an extra sum of squares F-test. SNP EC50 was greater in obese relative to lean (-2.931 ± 0.10 vs -3.746 ± 0.18 Log[SNP]M, P<0.001); however, there was no difference in MCh EC50 between groups (-3.796 ± 0.23 vs -3.852 ± 0.25 Log[MCh]M, P=0.81). Additionally, baseline and maximal CVC in both sites were similar between groups (all P>0.05). These results suggest attenuated endothelium-independent response to nitric oxide while endothelium-dependent vasodilation function is maintained.

Acute flavanol consumption improves the cerebral vasodilatory capacity in college-aged African Americans.

NEW FINDINGS: What is the central question of this study? The purpose was to determine whether acute flavanol consumption improves cerebral vasodilatory capacity during rebreathing-induced hypercapnia in African Americans. What is the main finding and its importance? The reduced cerebral vasodilatory response to hypercapnia in young healthy African Americans was improved acutely following consumption of a flavanol-rich beverage. This may have important clinical implications regarding racial differences in cerebrovascular disease risk and possible interventional approaches to offset this risk. African Americans (AAs) have increased risk for cardiovascular and cerebrovascular disease. African Americans have attenuated cerebral vasodilator capacity during hypercapnia relative to Caucasian Americans (CAs). This study tested the hypothesis, using a placebo-controlled crossover design, that acute flavanol consumption improves the range of change in cerebral vascular conductance [CVCI, (a)] and the maximal CVCI (y0) achieved during rebreathing-induced increases in end-tidal carbon dioxide tension. Fourteen college-aged AAs and 14 CAs participated. Both a and y0 were lower in AAs prior to flavanols (for a, AAs, 46 ± 16 versus CAs, 74 ± 18% CVCI, P < 0.001; and for y0, AAs, 151 ± 18 versus CAs, 176 ± 20% CVCI, P = 0.002); however, these variables were increased after flavanols such that there were no differences between groups (for a, AAs, 64 ± 19 versus CAs, 72 ± 22% CVCI, P = 0.35; and for y0, AAs, 166 ± 22 versus CAs, 176 ± 22% CVCI, P = 0.26). Both a and y0 were also lower in AAs prior to placebo (for a, AAs, 52 ± 19 versus CAs, 76 ± 15% CVCI, P = 0.002; and for y0, AAs, 156 ± 20 versus CAs, 177 ± 21% CVCI, P = 0.015), and these differences remained following placebo (for a, AAs, 52 ± 17 versus CAs, 80 ± 20% CVCI, P < 0.001; and for y0, AAs, 152 ± 18 versus CAs, 181 ± 25% CVCI, P = 0.003). These data suggest that acute flavanol consumption improves cerebral vasodilatory capacity during hypercapnia in AAs.

Attenuated cerebral vasodilatory capacity in response to hypercapnia in college-aged African Americans.

NEW FINDINGS: What is the central question of this study? The main purpose of this investigation is to determine whether there is a difference in cerebral vasodilatory capacity in response to rebreathing-induced hypercapnia between African Americans and Caucasian Americans. What is the main finding and its importance? College-aged African Americans have reduced cerebral vasodilatory capacity during hypercapnia when compared with Caucasian counterparts, a finding that suggests cerebral vascular dysfunction in this population. These findings may contribute to the understanding of the greater prevalence of cerebral vascular disease in this population. African Americans (AAs) have increased risk for cardiovascular, cerebral vascular and metabolic disease, including hypertension, stroke, coronary artery disease, metabolic syndrome and type II diabetes, relative to Caucasian Americans (CAs). While it is accepted that endothelial function is impaired in AAs, less is known regarding their cerebral vasodilatory capacity in response to hypercapnia. We hypothesized that AAs have a reduction in the total range of change in cerebral blood flow velocity (CBFV) measured in the middle cerebral artery and an index of cerebral vascular conductance (CVCI) in response to changes in the partial pressure of end-tidal carbon dioxide (P(ET,CO2)) during rebreathing-induced hypercapnia when compared with CAs. Twenty-one healthy, college-aged AA (10 male) and 21 age- and sex-matched CA (10 male) subjects participated in this study. A four-parameter logistic regression was used for curve fitting the responses of CBFV and CVCI relative to changes in P(ET,CO2). The total ranges of change in CBFV (101 ± 18 versus 69 ± 23%; P < 0.001) and CVCI (83 ± 21 versus 58 ± 21%; P < 0.001) as well as the maximal increase in CBFV (205 ± 24 versus 169 ± 24%; P < 0.001) and CVCI (188 ± 30 versus 154 ± 19%; P < 0.001) were reduced during hypercapnia in AAs relative to CAs despite a similar increase in P(ET,CO2) (change, 15 ± 3 versus 15 ± 3 mmHg; P = 0.65). In conclusion, these data indicate that AAs have attenuated cerebral vascular capacity to respond to hypercapnia when compared with CAs.