Hormonal intrauterine devices and heat exchange during exercise.

Synthetic progestins in oral contraceptives are thought to blunt heat dissipation by reducing skin blood flow and sweating. However, whether progestin-releasing intrauterine devices (IUDs) modulate heat loss during exercise-heat stress is unknown. We used direct calorimetry to measure whole-body total (dry + evaporative) heat loss in young, physically active women (mean (SD); aged 24 (4) years, V ̇ O 2 peak ${\dot V_{{{\mathrm{O}}_{\mathrm{2}}}{\mathrm{peak}}}}$ 39.3 (5.3) ml/kg/min) with (IUD; n = 19) and without (Control; n = 17) IUDs in the follicular and luteal phases of the menstrual cycle during light- and moderate-intensity exercise at fixed rates of heat production (∼175 and ∼275 W/m2 ) in 30°C, ∼21% relative humidity. Between-group and -phase differences were evaluated using traditional hypothesis testing and statistical equivalence testing within pre-determined bounds (±11 W/m2 ; difference required to elicit a ±0.3°C difference in core temperature over 1 h) in each exercise bout. Whole-body total heat loss was statistically equivalent between groups within ±11 W m-2 (IUD-Control [90% CIs]; Light: -2 [-8, 5] W/m2 , P = 0.007; Moderate: 0 [-6, 6] W/m2 , P = 0.002), as were dry and evaporative heat loss (P ≤ 0.023), except for evaporative heat loss during moderate-intensity exercise (equivalence: P = 0.063, difference: P = 0.647). Whole-body total and evaporative heat loss were not different between phases (P ≥ 0.267), but dry heat loss was 3 [95% CIs: 1, 5] W/m2 greater in the luteal phase (P ≤ 0.022). Despite this, all whole-body heat loss outcomes were equivalent between phases (P ≤ 0.003). These findings expand our understanding of the factors that modulate heat exchange in women and provide valuable mechanistic insight of the role of endogenous and exogenous female sex hormones in thermoregulation. KEY POINTS: Progestin released by hormonal intrauterine devices (IUDs) may negatively impact heat dissipation during exercise by blunting skin blood flow and sweating. However, the influence of IUDs on thermoregulation has not previously been assessed. We used direct calorimetry to show that IUD users and non-users display statistically equivalent whole-body dry and evaporative heat loss, body heat storage and oesophageal temperature during moderate- and high-intensity exercise in a warm, dry environment, indicating that IUDs do not appear to compromise exercise thermoregulation. However, within IUD users and non-users, dry heat loss was increased and body heat storage and oesophageal temperature were reduced in the luteal compared to the follicular phase of the menstrual cycle, though these effects were small and unlikely to be practically meaningful. Together, these findings expand our understanding of the factors that modulate heat exchange in women and have important practical implications for the design of future studies of exercise thermoregulation.

Interaction between local blood flow and tolerance to prolonged pain in the elderly.

PURPOSE: We aimed to explore the link between local vasodilation and pain perception in elderly subjects, testing the hypothesis that altered local cutaneous blood flow participates in the decrease in pain tolerance with age. METHOD: Sixty-eight young and 83 older participants performed a pain tolerance test in which they hold their hand in an airtight box in which air temperature was regulated at 65 °C until the pain became unbearable. Participants continuously estimated pain intensity. Skin temperature and local blood flow in the box-exposed hand were continuously monitored. RESULTS: In the young group, 97% of subjects resisted pain until the end of the test, whereas only 53% in the elderly group managed to do so, indicating that pain tolerance is impaired in the elderly. Among all participants, the skin temperature associated with the first pain sensation was below the threshold for nociceptor activation (43 °C). Interestingly, blood flow in the elderly group was correlated with pain judgment, whereas no such correlation was observed in the young. CONCLUSION: Our results suggest that the local vasodilator response induced by local heating may be involved in pain perception and may influence thermal pain tolerance with aging. These results could contribute to a better understanding of vascular deficits and the development of chronic pain in vascular pathologies.

Reactivity of observers' facial skin blood flow depending on others' facial expressions and blushing.

Facial skin blood flow (SkBF) has attracted attention as an autonomic indicator because it influences facial colour, which informs others of emotional states, and facial temperature related to social anxiety. Previous studies have examined the facial SkBF in people experiencing emotions; however, facial SkBF changes in the observers of emotions are poorly understood. Our study clarified facial SkBF changes related to observing others' emotions by comparing the changes with other physiological indices. Thirty healthy participants (24 females; mean age: 22.17) observed six types of facial expressions (neutral, angry, and embarrassed expressions with and without facial blushing) and rated the emotional intensity of the other person. We measured their facial SkBF, finger SkBF, and cardiac RR interval as they made their observations. Facial SkBF generally decreased in relation to observing emotional faces (angry and embarrassed faces) and significantly decreased for angry expressions with blushing. None of the participants noticed blushing of facial stimuli. For the RR interval and finger SkBF, there was no variation depending on the observed facial expressions, although there was a general increase related to observation. These results indicated that facial SkBF is sensitive and reactive to emotional faces-especially angry faces with blushing- compared with other autonomic indices. The facial SkBF changes were not related to either RR interval changes or the intensity rating, suggesting that facial SkBF changes may be caused by vasoconstriction and have potential functions for our emotions. The decrease in facial SkBF may have a role in calming observers by preventing them from adopting the same emotional state as a person with intense anger. These findings clarify daily facial SkBF fluctuations and their relationship with our emotional processing in interpersonal situations.

Short-term cocoa bioflavanol supplementation does not improve cold-induced vasodilation in young healthy adults.

PURPOSE: Cold-induced vasodilation (CIVD) is an oscillatory rise in blood flow to glabrous skin that occurs in cold-exposed extremities. Dietary flavanols increase bioavailable nitric oxide, a proposed mediator of CIVD through active vasodilation and/or withdrawal of sympathetic vascular smooth muscle tone. However, no studies have examined the effects of flavanol intake on extremity skin perfusion during cold exposure. We tested the hypothesis that acute and 8-day flavanol supplementation would augment CIVD during single-digit cold water immersion (CWI). METHODS: Eleven healthy adults (24 ± 6 years; 10 M/1F) ingested cocoa flavanols (900 mg/day) or caffeine- and theobromine-matched placebo for 8 days in a double-blind, randomized, crossover design. On Days 1 and 8, CIVD was assessed 2 h post-treatment. Subjects immersed their 3rd finger in warm water (42 °C) for 15 min before CWI (4 °C) for 30 min, during which nail bed and finger pad skin temperature were measured. RESULTS: Flavanol ingestion had no effect on CIVD frequency (Day 1, Flavanol: 3 ± 2 vs. Placebo: 3 ± 2; Day 8, Flavanol: 3 ± 2 vs. Placebo: 3 ± 1) or amplitude (Day 1, Flavanol: 4.3 ± 1.7 vs. Placebo: 4.9 ± 2.6 °C; Day 8, Flavanol: 3.9 ± 1.9 vs. Placebo: 3.9 ± 2.0 °C) in the finger pad following acute or 8-day supplementation (P > 0.05). Furthermore, average, nadir, and apex finger pad temperatures during CWI were not different between treatments on Days 1 or 8 of supplementation (P > 0.05). Similarly, no differences in CIVD parameters were observed in the nail bed following supplementation (P > 0.05). CONCLUSION: These data suggest that cocoa flavanol ingestion does not alter finger CIVD. Clinical Trial Registration Clinicaltrials.gov Identifier: NCT04359082. April 24, 2020.

Transfusion increased skin blood flow when initially low in volume-resuscitated patients without acute bleeding.

Background: Alterations in skin blood flow is a marker of inadequate tissue perfusion in critically ill patients after initial resuscitation. The effects of red blood cell transfusions (RBCT) on skin perfusion are not described in this setting. We evaluated the effects of red blood cell transfusions on skin tissue perfusion in critically ill patients without acute bleeding after initial resuscitation. Methods: A prospective observational study included 175 non-bleeding adult patients after fluid resuscitation requiring red blood cell transfusions. Using laser Doppler, we measured finger skin blood flow (SBF) at skin basal temperature (SBFBT), together with mean arterial pressure (MAP), heart rate (HR), hemoglobin (Hb), central venous pressure (CVP), lactate, and central or mixed venous oxygen saturation before and 1 h after RBCT. SBF responders were those with a 20% increase in SBFBT after RBCT. Results: Overall, SBFBT did not significantly change after RBCT [from 79.8 (4.3-479.4) to 83.4 (4.9-561.6); p = 0.67]. A relative increase equal to or more than 20% in SBFBT after RBCT (SBF responders) was observed in 77/175 of RBCT (44%). SBF responders had significantly lower SBFBT [41.3 (4.3-279.3) vs. 136.3 (6.5-479.4) perfusion units; p < 0.01], mixed or central venous oxygen saturation (62.5 ± 9.2 vs. 67.3% ± 12.0%; p < 0.01) and CVP (8.3 ± 5.1 vs. 10.3 ± 5.6 mmHg; p = 0.03) at baseline than non-responders. SBFBT increased in responders [from 41.3 (4.3-279.3) to 93.1 (9.8-561.6) perfusion units; p < 0.01], and decreased in the non-responders [from 136.3 (6.5-479.4) to 80.0 (4.9-540.8) perfusion units; p < 0.01] after RBCT. Pre-transfusion SBFBT was independently associated with a 20% increase in SBFBT after RBCT. Baseline SBFBT had an area under receiver operator characteristic of 0.73 (95% CI, 0.68-0.83) to predict SBFBT increase; A SBFBT of 73.0 perfusion units (PU) had a sensitivity of 71.4% and a specificity of 70.4% to predict SBFBT increase after RBCT. No significant differences in SBFBT were observed after RBCT in different subgroup analyses. Conclusion: The skin blood flow is globally unaltered by red blood cell transfusions in non-bleeding critically ill patients after initial resuscitation. However, a lower SBFBT at baseline was associated with a relative increase in skin tissue perfusion after RBCT.

A century of exercise physiology: concepts that ignited the study of human thermoregulation. Part 2: physiological measurements.

In this, the second of four historical reviews on human thermoregulation during exercise, we examine the research techniques developed by our forebears. We emphasise calorimetry and thermometry, and measurements of vasomotor and sudomotor function. Since its first human use (1899), direct calorimetry has provided the foundation for modern respirometric methods for quantifying metabolic rate, and remains the most precise index of whole-body heat exchange and storage. Its alternative, biophysical modelling, relies upon many, often dubious assumptions. Thermometry, used for >300 y to assess deep-body temperatures, provides only an instantaneous snapshot of the thermal status of tissues in contact with any thermometer. Seemingly unbeknownst to some, thermal time delays at some surrogate sites preclude valid measurements during non-steady state conditions. To assess cutaneous blood flow, immersion plethysmography was introduced (1875), followed by strain-gauge plethysmography (1949) and then laser-Doppler velocimetry (1964). Those techniques allow only local flow measurements, which may not reflect whole-body blood flows. Sudomotor function has been estimated from body-mass losses since the 1600s, but using mass losses to assess evaporation rates requires precise measures of non-evaporated sweat, which are rarely obtained. Hygrometric methods provide data for local sweat rates, but not local evaporation rates, and most local sweat rates cannot be extrapolated to reflect whole-body sweating. The objective of these methodological overviews and critiques is to provide a deeper understanding of how modern measurement techniques were developed, their underlying assumptions, and the strengths and weaknesses of the measurements used for humans exercising and working in thermally challenging conditions.

Hesperetin-7-O-glucoside/ß-cyclodextrin Inclusion Complex Induces Acute Vasodilator Effect to Inhibit the Cold Sensation Response during Localized Cold-Stimulate Stress in Healthy Human Subjects: A Randomized, Double-Blind, Crossover, and Placebo-Controlled Study.

Hesperetin, a citrus flavonoid, exerts vasodilation and is expected to improve endothelial function and alleviate cold sensation by activating nervous system thermal transduction pathways. In this randomized, double-blind, crossover, and placebo-controlled study, the purpose was to assess the effect of an orally administered highly bioavailable soluble inclusion complex of hesperetine-7-O-glucoside with ß-cyclodextrin (HEPT7G/ßCD; SunActive® HES/HCD) on cold sensation response during localized cold-stimulated stress in healthy humans. A significant (p ≤ 0.05) dose-dependent increase in skin cutaneous blood flow following relatively small doses of HEPT7G/ßCD inclusion complex ingestion was confirmed, which led to a relatively effective recovery of peripheral skin temperature. The time delay of an increase in blood flow during rewarming varied significantly between low- and high-dose HEPT7G/ßCD inclusion complex consumption (e.g., 150 mg and 300 mg contain 19.5 mg and 39 mg of HEPT7G, respectively). In conclusion, the substantial alteration in peripheral skin blood flow observed during local cooling stress compared to placebo suggested that deconjugated hesperetin metabolites may have a distinct capacity for thermoregulatory control of human skin blood flow to maintain a constant body temperature during cold stress exposure via cutaneous vasodilation and vasoconstriction systems.

Excessive whole-body exposure to 28 GHz quasi-millimeter wave induces thermoregulation accompanied by a change in skin blood flow proportion in rats.

Introduction: Limited information is available on the biological effects of whole-body exposure to quasi-millimeter waves (qMMW). The aim of the present study was to determine the intensity of exposure to increase body temperature and investigate whether thermoregulation, including changes in skin blood flow, is induced in rats under whole-body exposure to qMMW. Methods: The backs of conscious rats were extensively exposed to 28 GHz qMMW at absorbed power densities of 0, 122, and 237 W/m2 for 40 minutes. Temperature changes in three regions (dorsal and tail skin, and rectum) and blood flow in the dorsal and tail skin were measured simultaneously using fiber-optic probes. Results: Intensity-dependent temperature increases were observed in the dorsal skin and the rectum. In addition, skin blood flow was altered in the tail but not in the dorsum, accompanied by an increase in rectal temperature and resulting in an increase in tail skin temperature. Discussion: These findings suggest that whole-body exposure to qMMW drives thermoregulation to transport and dissipate heat generated on the exposed body surface. Despite the large differences in size and physiology between humans and rats, our findings may be helpful for discussing the operational health-effect thresholds in the standardization of international exposure guidelines.

Greater post-exercise hypotension in healthy young untrained men after exercising in a hot compared to a temperate environment.

This research examined the effects of exercising in a hot compared to a temperate environment on post-exercise hemodynamics in untrained men. We hypothesized exercise in a hot compared to a temperate environment would elicit greater post-exercise hypotension, and this would be attributable to higher cutaneous vascular conductance and sweat loss, and lower heart rate variability (HRV) and cardiac baroreflex sensitivity (cBRS). In a randomized counterbalanced order, 12 untrained healthy men completed two trials involving 40-min leg-cycling exercise at either 23 °C (CON) or 35 °C (HOT). Post-exercise participants rested supine for 60 min at 23 °C whilst hemodynamic and thermoregulatory measurements were assessed. Post-exercise hypotension was greater after exercising in a hot than a temperate environment as indicated by a lower mean arterial pressure at 60 min recovery (CON 83 ± 5 mmHg, HOT 78 ± 5 mmHg, Mean difference [95% confidence interval], -5 [-8, -3] mmHg). Throughout recovery, cutaneous vascular conductance was higher, and cBRS and HRV were lower after exercising in a hot than in a temperate environment (P < 0.05). Sweat loss was greater on HOT than on CON (P < 0.001). Post-exercise hypotension after exercising in the hot environment was associated with sweat loss (r = 0.66, P = 0.02), and changes in cutaneous vascular conductance (r = 0.64, P = 0.03), and HRV (Root mean square of the successive difference in R-R interval [RMSSD]) r=0.75, P = 0.01 and and log high frequency [HF] r=0.66, P = 0.02), but not cBRS (all, r ≤ 0.2, P > 0.05). Post-exercise hypotension was greater after exercise in a hot compared to a temperate environment and may be partially explained by greater sweat loss and cutaneous vascular conductance, and lower HRV.

Cardiovascular responses to hot skin at rest and during exercise.

Integrative cardiovascular responses to heat stress during endurance exercise depend on various variables, such as thermal stress and exercise intensity. This review addresses how increases in skin temperature alter and challenge the integrative cardiovascular system during upright submaximal endurance exercise, especially when skin is hot (i.e. >38°C). Current evidence suggests that exercise intensity plays a significant role in cardiovascular responses to hot skin during exercise. At rest and during mild intensity exercise, hot skin increases skin blood flow and abolishes cutaneous venous tone, which causes blood pooling in the skin while having little impact on stroke volume and thus cardiac output is increased with an increase in heart rate. When the heart rate is at relatively low levels, small increases in heart rate, skin blood flow, and cutaneous venous volume do not compromise stroke volume, so cardiac output can increase to fulfill the demands for maintaining blood pressure, heat dissipation, and the exercising muscle. On the contrary, during more intense exercise, hot skin does not abolish exercise-induced cutaneous venoconstriction possibly due to high sympathetic nerve activities; thus, it does not cause blood pooling in the skin. However, hot skin reduces stroke volume, which is associated with a decrease in ventricular filling time caused by an increase in heart rate. When the heart rate is high during moderate or intense exercise, even a slight reduction in ventricular filling time lowers stroke volume. Cardiac output is therefore not elevated when skin is hot during moderate intensity exercise.

Application of Multiscale Sample Entropy in Assessing Effects of Exercise Training on Skin Blood Flow Oscillations in People with Spinal Cord Injury.

Spinal cord injury (SCI) causes a disruption of autonomic nervous regulation to the cardiovascular system, leading to various cardiovascular and microvascular diseases. Exercise training is an effective intervention for reducing risk for microvascular diseases in healthy people. However, the effectiveness of exercise training on improving microvascular function in people with SCI is largely unknown. The purpose of this study was to compare blood flow oscillations in people with spinal cord injury and different physical activity levels to determine if such a lifestyle might influence skin blood flow. A total of 37 participants were recruited for this study, including 12 athletes with SCI (ASCI), 9 participants with SCI and a sedentary lifestyle (SSCI), and 16 healthy able-bodied controls (AB). Sacral skin blood flow (SBF) in response to local heating at 42 °C for 50 min was measured using laser Doppler flowmetry. The degree of the regularity of blood flow oscillations (BFOs) was quantified using a multiscale entropy approach. The results showed that BFO was significantly more irregular in ASCI and AB compared to SSCI during the maximal vasodilation period. Our results also demonstrate that the difference in the regularity of BFOs between original SBF signal and phase-randomized surrogate time series was larger in ASCI and AB compared to SSCI. Our findings indicate that SCI causes a loss of complexity of BFOs and exercise training may improve complexity in people with SCI. This study demonstrates that multiscale entropy is a sensitive method for detecting differences between different categories of people with SCI and might be able to detect effects of exercise training related to skin blood flow.

Prefrontal NIRS signal is unaffected by forehead Doppler flux during incremental cycling exercise.

Near-infrared spectroscopy (NIRS) is used to measure tissue concentrations of oxyhemoglobin (O2 Hb) and deoxyhemoglobin (HHb). In the context of exercise, NIRS confers a higher signal-to-noise ratio than other neuroimaging techniques. However, part of the signal may be influenced by thermoregulatory hyperemia in the superficial cutaneous capillaries of the forehead. The degree to which NIRS signals during exercise reflect cerebral or extracerebral hemodynamic changes is a continuing source of controversy. However, the influence of skin blood flow may be attenuated depending on the NIRS technique (e.g., frequency domain machines with maximal optode separation distances >3.5 cm). The purpose of this study was to compare the changes in forehead skin blood flow and cerebral hemoglobin concentration during incremental exercise versus direct vasodilation of the forehead skin induced by gradual local heating. Thirty participants (12 females, 18 males; age: 20.8 ± 3.2 years; body mass index: 23.8 ± 3.7 kg·m-2 ) participated in the study. Forehead skin blood flow was quantified laser Doppler flux and absolute concentrations of cerebral O2 Hb and HHb were measured by NIRS. Local heating significantly increased the Doppler flux signal across time and these changes were significantly correlated with skin temperature. During incremental exercise, skin temperature, Doppler flux, O2 Hb and HHb increased however, the only significant change that was consistently correlated with Doppler flux was skin temperature. Therefore, a significant change in forehead skin blood flow may not significantly the NIRS hemoglobin data, depending on the type of NIRS device used.

Within-limb variation in skin pigmentation does not influence cutaneous vasodilation.

Ultraviolet radiation (UVR) exposure acutely reduces nitric oxide (NO)-dependent cutaneous vasodilation. In addition, increased constitutive skin melanin is associated with attenuated NO-dependent cutaneous vasodilation. However, the impact of within-limb variation in skin melanization, associated with seasonal UVR exposure, on NO-dependent cutaneous vasodilation is unknown. We investigated the effect of within-limb variation in skin melanin on NO-dependent cutaneous vasodilation. Intradermal microdialysis fibers were placed in the inner-upper arm, ventral forearm, and dorsal forearm of seven adults (33 ± 14 yr; 4 M/3 F) with constitutively light skin pigmentation. Melanin-index (M-index; an index of skin pigmentation), measured via reflectance spectrophotometry, confirmed differences in sun exposure among sites. A standardized local heating (42°C) protocol induced cutaneous vasodilation. After attaining a stable elevated blood flow plateau, 15 mM NG-nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) was infused to quantify the NO contribution. Laser-Doppler flowmetry (LDF) measured red cell flux and cutaneous vascular conductance (CVC = LDF/mean arterial pressure) and was normalized to maximal (%CVCmax; 28 mM sodium nitroprusside + 43°C local heating). Dorsal forearm M-index was higher [50.5 ± 11.8 au (arbitrary units)] compared with the ventral forearm (37.5 ± 7.4 au; P ≤ 0.03) and upper arm (30.0 ± 4.0 au; P ≤ 0.001) M-index. Cutaneous vasodilation responses to local heating were not different among sites (P ≥ 0.12). Importantly, neither the magnitude of the local heating plateau (dorsal: 85 ± 21%; ventral: 70 ± 21%; upper: 87 ± 15%; P ≥ 0.16) nor the NO-mediated component of that response (dorsal: 59 ± 15%; ventral: 54 ± 13%; upper: 55 ± 11%; P ≥ 0.79) was different among sites. These data suggest that within-limb differences in skin pigmentation secondary to seasonal UVR exposure do not alter NO-dependent cutaneous vasodilation.NEW & NOTEWORTHY Locally derived endothelial nitric oxide (NO) contributes to the full expression of cutaneous vasodilation responses. Acute ultraviolet radiation (UVR) exposure attenuates NO-mediated vasodilation of the cutaneous microvasculature. Our findings suggest that in constitutively lightly pigmented skin, variation in skin melanin due to seasonal exposure to UVR does not alter the NO contribution to cutaneous vasodilation. Seasonal UVR exposure does not impact the NO-mediated cutaneous microvascular function.

Influence of topical capsaicin cream on thermoregulation and perception during acute exercise in the heat.

PURPOSE: Determine if topical capsaicin, a transient receptor potential vanilloid heat thermoreceptor activator, alters thermoregulation and perception when applied topically prior to thermal exercise. METHODS: Twelve subjects completed 2 treatments. Subjects walked (1.6 m s-1, 5% grade) for 30 min in the heat (38 °C, 60% relative humidity) with either a capsaicin (0.025% capsaicin) or control cream applied to the upper (shoulder to wrist) and lower (mid-thigh to ankle) limbs covering ∼50% body surface area. Skin blood flow (SkBF), sweat (rate, composition), heart rate, temperature (skin, core), and perceived thermal sensation were measured prior to and during exercise. RESULTS: The relative change in SkBF was not different between treatments at any time point (p = 0.284). There were no differences in sweat rate between the capsaicin (1.23 ± 0.37 L h-1) and control (1.43 ± 0.43 L h-1, p = 0.122). There were no differences in heart rate between the capsaicin (122 ± 38 beats·min-1) and control (125 ± 39 beats·min-1, p = 0.431). There were also no differences in weighted surface (p = 0.976) or body temperatures (p = 0.855) between the capsaicin (36.0 ± 1.7 °C, 37.0 ± 0.8 °C, respectively) and control (36.0 ± 1.6 °C, 36.9 ± 0.8 °C, respectively). The capsaicin treatment was not perceived as hotter than the control treatment until minute 30 of exercise (2.8 ± 0.4, 2.5 ± 0.5, respectively, p = 0.038) CONCLUSIONS: Topical capsaicin application does not alter whole-body thermoregulation during acute exercise in the heat despite perceiving the treatment as hotter late in exercise.

Enhanced Contraction of Arterial Smooth Muscle Cell in Skin Artery Is Sensitive to Hyperpolarization Mediated by BKCa Channel in Chronic Constriction Injury Model Rat.

Previous our study found that improvement of skin blood flow associated with neuropathic pain using vasodilators is useful for alleviation of neuropathic pain. In this study, we aimed to elucidate the mechanism underlying enhanced vasorelaxation induced by vasodilators, which increase cAMP and cyclic guanosine monophosphate (cGMP), in chronic constriction injury model rat. We assessed vasorelaxation effect of vasodilators by measurement of isometric contraction in isolated plantar artery from chronic constriction injury of sciatic nerve model rats. Nifedipine, a voltage-dependent Ca2+ channel inhibitor, NS1619, Ca2+-activated K+ (BKCa) channel opener, and diazoxide, an ATP-sensitive potassium channel opener, -induced vasorelaxation in ipsilateral plantar artery was enhanced compared to the these in contralateral plantar artery. Sodium nitroprusside (SNP), a nitric oxide (NO) donor, and substance P, a NK1 receptor agonist, caused vasorelaxation in both ipsilateral and contralateral artery. The vasorelaxation induced by SNP and substance P in ipsilateral artery is enhanced compared to the these in contralateral artery. Isoprenaline, a ß adrenoceptor agonist, and salbutamol, a ß2 adrenoceptor agonist, caused strong vasorelaxation in ipsilateral artery but not in contralateral artery. Iberiotoxin, a BKCa channel inhibitor, prominently suppressed the enhanced vasorelaxation induced by SNP, substance P, isoprenaline and salbutamol. In summary, the enhanced contraction of arterial smooth muscle cell in skin artery is sensitive to hyperpolarization in chronic constriction injury model rat. Furthermore, ß adrenoceptor agonist would be a good drug to improve the decreased skin blood flow because it has selective vasorelaxation to ipsilateral plantar artery.

Cholinergic nerve contribution to cutaneous active vasodilation during exercise is similar to whole body passive heating.

Sympathetic cholinergic nerve cotransmission is widely accepted as the mechanism of cutaneous active vasodilation (CAVD) during whole body passive heating (passive heating). However, recent research suggests that there may be mechanistic differences in CAVD to heating, depending on the modality of thermal loading. It is unknown whether sympathetic cholinergic cotransmission explains CAVD during exercise. This study sought to confirm the role of cholinergic nerves in CAVD during passive heating and expand these findings to exercise. It was hypothesized that CAVD during both exercise and passive heating would be abolished by cholinergic nerve blockade. Eight young (18-30 yr) recreationally active individuals exercised (1 h seated cycling at 60% V̇o2peak) and were passively heated (∼1 h seated passive heating with mean skin temperature clamped at 39°C by water-perfused suit), in randomized order on separate days. Cholinergic nerves were blocked via Botox ∼2 wk prior to the study. Skin blood flow was assessed using laser Doppler flowmetry and expressed as percent of maximum cutaneous vascular conductance (%CVCmax). At the end of exercise/passive heating, internal temperature had increased by ∼0.7°C. The %CVCmax at the Botox-treated sites (exercise: 19 ± 6 and passive heating: 15 ± 14%CVCmax) was significantly less (P < 0.001) than at the untreated sites (exercise: 35 ± 11 and passive heating: 38 ± 6%CVCmax), but there were no differences between exercise and passive heating (modality, P = 0.909; modality-Botox interaction, P = 0.230). We conclude that CAVD during both exercise and passive heating is mediated by sympathetic cholinergic nerves, a critical thermoregulatory mechanism that appears to be independent of the thermal loading modality.NEW & NOTEWORTHY Our study establishes the primacy of cholinergic nerves to cutaneous active vasodilation during exercise and confirms this model during passive heating using a crossover study design. In addition, the mode of heating, whether passive or exercise induced, did not change the sensitivity of the cholinergic component of the thermoeffector response to increased internal temperature. Thus, cutaneous active vasodilator nerves are responsible for similar skin blood flow responses regardless of how thermal loading is accomplished.

Influence of acute beetroot juice supplementation on cold-induced vasodilation and fingertip rewarming.

PURPOSE: Vasoactive ingredients in beetroot (BR) such as nitrate are known to induce vasodilation in temperate conditions. This study investigated the effect of BR ingestion on cold induced vasodilation (CIVD) and rewarming of finger skin temperature (Tfing) during and after hand immersion in cold water. METHODS: Twenty healthy males (mean ± SD; age 22.2 ± 0.7 years, height 172.6 ± 6.0 cm, body mass 61.3 ± 11.7 kg) repeated a hand cold water immersion test twice with prior BR or water beverage ingestion (randomised order). They rested for 2 h in thermoneutral conditions (27 °C, 40% relative humidity) after consuming the beverage, then immersed their non-dominant hand in 8 °C water for 30 min. They then rewarmed their hand in the ambient air for 20 min. Skin temperature at seven body sites, Tfing, finger skin blood flow (SkBFfing), and blood pressure were measured. RESULTS: During hand immersion parameters of CIVD (Tfing and SkBFfing) were not different between BR and water conditions although skin temperature gradient from proximal to distal body sites was significantly smaller with BR (P < 0.05). During rewarming, SkBFfing and cutaneous vascular conductance were significantly higher with BR than with water (P < 0.05). The rewarming speed in Tfing and SkBFfing was significantly faster with BR at 15- (BR 1.24 ± 0.22 vs water 1.11 ± 0.26 °C/min) and 20-min rewarming (P < 0.05). Additionally, individuals with slower rewarming speed with water demonstrated accelerated rewarming with BR supplementation. CONCLUSION: BR accelerated rewarming in Tfing and SkBFfing after local cold stimulus, whereas, CIVD response during hand cold immersion was not affected by BR ingestion.

Involvement of nitric oxide synthase and reactive oxygen species in TRPA1-mediated cutaneous vasodilation in young and older adults.

OBJECTIVE: To investigate the nitric oxide synthase (NOS) and reactive oxygen species (ROS) contributions of the cutaneous vasodilator response to transient receptor potential ankyrin-1 channel (TRPA1) activation in young and older adults. MATERIALS AND METHODS: In sixteen young (20 ± 2 years, 8 females) and sixteen older adults (61 ± 5 years, 8 females), cutaneous vascular conductance normalized to maximum vasodilation (%CVCmax) was assessed at four dorsal forearm skin sites continuously perfused via microdialysis with: 1) vehicle solution (Control, 2 % dimethyl sulfoxide, 2 % Ringer, 96 % propylene glycol), 2) 10 mM Ascorbate (non-specific ROS inhibitor), 3) 10 mM L-NAME (non-specific NOS inhibitor), or 4) Ascorbate+L-NAME. The TRPA1 agonist cinnamaldehyde was co-administered at all sites [0 % (baseline), 2.9 %, 8.8 %, 26.4 %; ≥ 30 min per dose]. RESULTS: %CVCmax was not different between groups for Control, L-NAME, and Ascorbate (all p > 0.05). However, there were significant main dose effects for each site wherein %CVCmax was greater than baseline from 2.9 % to 26.4 % cinnamaldehyde for Control and Ascorbate, and at 26.4 % cinnamaldehyde for L-NAME and Ascorbate+L-NAME (all p < 0.05). For Ascorbate+L-NAME, there was a significant main group effect, wherein perfusion was 6 %CVCmax [95% CI: 2, 11, p < 0.05] greater in the older compared to the young group across all cinnamaldehyde doses. There was a significant main site effect for area under the curve wherein L-NAME and Ascorbate+L-NAME were lower than Control and Ascorbate across groups (all p < 0.05). CONCLUSION: The NOS-dependent cutaneous vasodilator response to TRPA1 activation is maintained in older adults, with no detectable contribution of ascorbate-sensitive ROS in either age group.

Reliability of laser-Doppler flowmetry derived measurements of forearm and calf cutaneous vasodilation during gradual local heating in young adults.

OBJECTIVES: Evaluate reliability of laser-Doppler flowmetry derived cutaneous vasodilation on the upper and lower limbs during gradual local heating. METHODS: In twenty-eight young adults (21 (SD 3) years, 14 females), absolute cutaneous vascular conductance (CVCabs) and CVC normalized to maximum vasodilation at 44 °C (%CVCmax) were assessed at two adjacent sites on each of the forearm and calf during gradual local skin heating (33-42 °C at 1 °C·5 min-1) for two identical trials (∼1 week apart). Responses were assessed for baseline, the steady-state heating plateau at 42 °C and the span (i.e. plateau-baseline). RESULTS: Between-day reliability was characterized as measurement consistency across trials. Within-day reliability was characterized as within-limb measurement consistency across adjacent skin sites. Between- and within-day absolute reliability (coefficient of variation) generally improved with heating, from poor (>25 %) at baseline to good (<10 %) for %CVCmax and moderate (10-25 %) for CVCabs for plateau and span. However, relative reliability (intraclass correlation coefficient) was generally not acceptable (<0.70) for any condition. Responses were generally consistent for females and males and there were no major forearm and calf differences. CONCLUSIONS: Consistency of CVC estimates improved during gradual local heating with negligible limb and sex differences, which are important considerations for experimental design and interpretation.

Effects of sensory nerve blockade on cutaneous microvascular responses to ischemia-reperfusion injury.

OBJECTIVE: Examine the effects of sensory nerve blockade on cutaneous post-occlusive reactive hyperemia (PORH) and local thermal hyperemia (LTH) following prolonged upper limb ischemia. MATERIALS AND METHODS: In nine males [28 years (standard deviation:6)], volar forearm skin blood flux normalized to maximum vasodilation (%SkBFmax) was assessed at control (CTRL) and sensory nerve blockade (EMLA) treated sites during the PORH response following 20-min of complete arm ischemia and during rapid LTH (33-42 °C, 1 °C·20 s-1, held for ~30-min + 20-min at 44 °C) before and after ischemia-reperfusion (IR) injury. RESULTS: EMLA increased mean [95 % confidence-interval] PORH amplitude by 21%SkBFmax ([9,33]; p = 0.003), delayed time to peak by 111 s ([40,182]; p = 0.007) and increased area under the curve by 19,462%SkBFmax·s ([11,346,27,579]; p < 0.001) compared to CTRL. For LTH, EMLA delayed onset time by 76 s ([46,106]; p < 0.001) Pre-IR and by 46 s ([27,65]; p < 0.001) Post-IR compared to CTRL. Post-IR onset time was delayed for CTRL by 26 s ([8,43]; p = 0.007), but was not different for EMLA (p > 0.050) compared to Pre-IR. EMLA delayed time to initial peak by 24 s ([4,43]; p = 0.022, Main time effect) and it attenuated the initial peak by 27%SkBFmax ([12,43]; p = 0.002) Pre-IR and by 16%SkBFmax ([3,29]; p = 0.020) post-IR compared to CTRL. Post-IR, the initial peak was not different for CTRL (p > 0.050), but it was increased by 16%SkBFmax ([5,26]; p = 0.005) for EMLA compared to Pre-IR. Neither EMLA nor IR altered the steady-state heating plateau (all p > 0.050). CONCLUSION: For the current model of IR injury, sensory nerves appear to have a negligible influence on the LTH response in non-glabrous forearm skin once vasodilation has been initiated.