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Introduction: Hyperthermia impairs various physiological functions and physical performance. We examined the effects of cutaneous administration with an overthe-counter (OTC) analgesic cream containing 20% methyl salicylate and 6% Lmenthol 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 inCON (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. [ABSTRACT FROM AUTHOR]

Control of cutaneous circulation is critically important to maintain thermoregulation, especially in individuals with cervical spinal cord injury (CSCI) who have no or less central thermoregulatory drive. However, the peripheral vasoconstrictor mechanism and capability have not been fully investigated after CSCI. Post- and presynaptic sensitivities of the cutaneous vasoconstrictor system were investigated in 8 CSCI and 7 sedentary able-bodied (AB) men using an intradermal microdialysis technique. Eight doses of norepinephrine (NE, 10-8 to 10-1 M) and five doses of tyramine (TY, 10-8, 10-5 to 10-2 M) were administered into the anterior right and left thigh, respectively. Endogenous catecholamines, noradrenaline, and dopamine, collected at the TY site, were determined by high-performance liquid chromatography with electrochemical detection. Regardless of vasoconstrictor agents, cutaneous vascular conductance decreased dose-dependently and responsiveness was similar between the groups (NE: Group P = 0.255, Dose P = 0.014; TY: Group P = 0.468, Dose P < 0.001), whereas the highest dose of each drug induced cutaneous vasodilation. Administration of TY promoted the release of noradrenaline and dopamine in both groups. Notably, the amount of noradrenaline released was similar between the groups (P = 0.819), although the concentration of dopamine was significantly greater in individuals with CSCI than in AB individuals (P = 0.004). These results suggest that both vasoconstrictor responsiveness and neural functions are maintained after CSCI, and dopamine in the skin is likely to induce cutaneous vasodilation. [ABSTRACT FROM AUTHOR]

Abstract Background Because carbon dioxide (CO2)-enriched water causes cutaneous vasodilation, immersion in CO2-enriched water facilitates heat transfer from the body to the water or from the water to the body. Consequently, immersion in CO2-enriched water raises or reduces body temperature faster than immersion in fresh water. However, it takes time to dissolve CO2 in tap water and because the dissolved CO2 concentration decreases over time, the actual CO2 concentration is likely lower than the stated target concentration. However, it is unclear whether water containing a lower CO2 concentration would also cool the body faster than fresh water after body temperature had been increased. Methods Ten healthy males (mean age = 20 ± 1 years) participated in the study. Participants were first immersed for 15 min in a tap water bath at 40 °C to raise body temperature. They then moved to a tap water or CO2-enriched water bath at 30 °C to reduce body temperature. The CO2 concentration was set at 500 ppm. The present study measured cooling time and cooling rate (slope of the regression line relating auditory canal temperature (T ac) to cooling time) to assess the cooling effect of CO2-enriched water immersion. Results Immersion in 40 °C tap water caused T ac to rise 0.64 ± 0.25 °C in the tap water session and 0.62 ± 0.27 °C in the CO2-enriched water session (P > 0.05). During the 30 °C water immersion, T ac declined to the baseline within 13 ± 6 min in tap water and 10 ± 6 min in CO2-enriched water (P > 0.05). Cooling rates were 0.08 ± 0.06 °C/min in tap water and 0.08 ± 0.04 °C/min in CO2-enriched water (P > 0.05). Conclusions CO2-enriched water containing 500 ppm CO2 did not cool faster than tap water immersion. This suggests that when the water temperature is 30 °C, a CO2 concentration of 500 ppm is insufficient to obtain the advantageous cooling effect during water immersion after body temperature has been increased.

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 exerciseinduced 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. [ABSTRACT FROM AUTHOR]

Summary: When racehorses fail to thermoregulate effectively, whether due to intrinsic or extrinsic factors, a condition called exertional heat illness (EHI) may occur, which can be life‐threatening and represents a significant welfare issue. Horses usually become affected in the recovery phase soon after racing, so that a knowledge of the 'normal' thermoregulatory processes which operate at this time and their variations is essential to enable early detection of EHI. Racing in hot or warm and humid weather conditions represents the upper extreme of thermoregulatory variations, and observations on how horses normally recover at the racetrack may provide a clearer perspective on the physiology of that process for all sports horses. This review focuses on the post‐exercise thermoregulatory capacity of the Thoroughbred racehorse, with a view to understanding the physiological mechanisms that should efficiently dissipate excess heat. The clinical manifestations of exertional heat illness are due to inadequate or harmful physiological responses, and if recognised and treated early can be effectively curtailed. [ABSTRACT FROM AUTHOR]

Background: Because carbon dioxide (CO2)-enriched water causes cutaneous vasodilation, immersion in CO2-enriched water facilitates heat transfer from the body to the water or from the water to the body. Consequently, immersion in CO2-enriched water raises or reduces body temperature faster than immersion in fresh water. However, it takes time to dissolve CO2 in tap water and because the dissolved CO2 concentration decreases over time, the actual CO2 concentration is likely lower than the stated target concentration. However, it is unclear whether water containing a lower CO2 concentration would also cool the body faster than fresh water after body temperature had been increased. Methods: Ten healthy males (mean age = 20 ± 1 years) participated in the study. Participants were first immersed for 15 min in a tap water bath at 40 °C to raise body temperature. They then moved to a tap water or CO2-enriched water bath at 30 °C to reduce body temperature. The CO2 concentration was set at 500 ppm. The present study measured cooling time and cooling rate (slope of the regression line relating auditory canal temperature (Tac) to cooling time) to assess the cooling effect of CO2-enriched water immersion. Results: Immersion in 40 °C tap water caused Tac to rise 0.64 ± 0.25 °C in the tap water session and 0.62 ± 0.27 °C in the CO2-enriched water session (P > 0.05). During the 30 °C water immersion, Tac declined to the baseline within 13 ± 6 min in tap water and 10 ± 6 min in CO2-enriched water (P > 0.05). Cooling rates were 0.08 ± 0.06 °C/min in tap water and 0.08 ± 0.04 °C/min in CO2-enriched water (P > 0.05). Conclusions: CO2-enriched water containing 500 ppm CO2 did not cool faster than tap water immersion. This suggests that when the water temperature is 30 °C, a CO2 concentration of 500 ppm is insufficient to obtain the advantageous cooling effect during water immersion after body temperature has been increased. [ABSTRACT FROM AUTHOR]

Niacin is effective in treating dyslipidemias but causes cutaneous vasodilation or flushing, a side effect that limits its clinical use. Blocking prostaglandins in humans reduces but does not consistently eliminate flushing, indicating additional mechanisms may contribute to flushing. The transient receptor potential vanilloid 1 (TRPV1) channel, when activated, causes cutaneous vasodilation and undergoes tachyphylaxis similar to that seen with niacin. Using a murine model, early phase niacin-induced flushing was examined and TRPV1 channel involvement demonstrated using pharmacologic blockade, desensitization, and genetic knockouts (TRPV1 KO). The TRPV1 antagonist AMG9810 reduced the magnitude of the initial and secondary peaks and the rapidity of the vasodilatory response (slope). TRPV1 desensitization by chronic capsaicin reduced the initial peak and slope. TRPV1 KO mice had a lower initial peak, secondary peak, and slope compared with wild-type mice. Chronic niacin reduced the initial peak, secondary peak, and slope in wild-type mice but had no effect in knockout mice. Furthermore, chronic niacin diminished the response to capsaicin in wild-type mice. Overall, these data demonstrate an important role for TRPV1 channels in niacin-induced flushing, both in the acute response and with chronic administration. That niacin-induced flushing is a complex cascade of events, which should inform pharmacological intervention against this side effect.

Purpose: To examine the cooling effect of lower body immersion with CO2-rich water after passive heating. Methods: Ten male subjects immersed in 40°C of tap water for 15 min to increase body temperature. After that, they immersed their lower body in 25 °C of tap water or CO2-rich water to decrease body temperature. Results: During cooling, there was no significant difference in sublingual temperature between tap water session and CO2-rich water session. The cooling times were 11 ± 4 min in tap water session and 10 ± 3 min in CO2-rich water session (P > 0.05). The cooling rates were -0.13 ± 0.07 °C/min in tap water session and -0.16 ± 0.07 °C/min in CO2-rich water session (P > 0.05). On the other hand, mean skin temperature, thigh skin temperature, and thigh skin blood flow were significantly higher in CO2-rich water session than in tap water session during cooling (P < 0.05). There were no significant differences in thermal comfort and thermal sensation between tap water session and CO2-rich water session. Discussion: Lower body immersion in CO2-rich water increased skin blood flow, resulting in higher skin temperature. However, that could not lead to higher cooling effect. These results suggest that it is important to augment body surface area to be cooled to keep cooling effect of CO2-rich water immersion. [ABSTRACT FROM AUTHOR]

Exposure to hot environments augments cutaneous vasodilation and sweating during exercise compared with these responses in cooler environments. The effects of hypobaric hypoxia on these responses are less clear, as are the effects of heat and simulated altitude combined. We evaluated the individual and potential additive effects of environmental heat and hypobaric hypoxia on skin blood flow and sweating responses during exercise. Thirteen volunteers (11 M, 2 F; age 25.3 ± 6.1 yr; height 177 ± 9 cm; weight 81.2 ± 16.8 kg) completed 30 min of steady-state (SS) exercise on a cycle ergometer at 50% VO2peak during four separate conditions: 1) sea level thermoneutral (SLTN; 250 m, 20°C, 30-50% RH), 2) sea level hot (SLH; 250 m, 35°C, 30% RH), 3) simulated altitude thermoneutral (ATN; 3,000 m, 20°C, 30-50% RH), and 4) simulated altitude hot (AH; 3,000 m, 35°C, 30% RH). Skin blood flow and local sweating rate (LSR) were recorded on the ventral forearm. During exercise, SS cutaneous vascular conductance in AH (63 ± 31% peak) and SLH (52 ± 19% peak) were significantly higher than both SLTN (20 ± 9% peak, P<0.001) and ATN (25 ± 12% peak, P<0.05) but were not different from each other (P > 0.05). SS LSR was similarly increased in the hot environments but unaffected by simulated altitude. We propose that multiple antagonistic mechanisms during exposure to 3,000-m simulated altitude result in no net effect on skin blood flow or sweating responses during exercise in thermoneutral or hot environments. [ABSTRACT FROM AUTHOR]

It has previously been shown that high dietary salt impairs vascular function independent of changes in blood pressure. Rodent studies suggest that NADPH-derived reactive oxygen species mediate the deleterious effect of high salt on the vasculature, and here we translate these findings to humans. Twenty-nine healthy adults (34 ± 2 yr) participated in a controlled feeding study. Participants completed 7 days of a low-sodium diet (LS; 20 mmol sodium/day) and 7 days of a high-sodium diet (HS; 300 mmol sodium/day) in random order. All participants were salt resistant, defined as a ≤5-mmHg change in 24-h mean BP determined while on the LS and HS diets. Laser Doppler flowmetry was used to assess cutaneous vasodilation in response to local heating (42°C) during local delivery of Ringer's (n = 29), 20 mM ascorbic acid (AA; n = 29), 10 µM Tempol (n = 22), and 100 µM apocynin (n = 22). Additionally, endothelial cells were obtained in a subset of participants from an antecubital vein and stained for nitrotyrosine (n = 14). Cutaneous vasodilation was attenuated by the HS diet compared with LS [LS 93.0 ± 2.2 vs. HS 86.8 ± 2.0 percentage of maximal cutaneous vascular conductance (%CVCmax); P < 0.05] and was restored by AA during the HS diet (AA 90.7 ± 1.2%CVCmax; P < 0.05 vs. HS). Cutaneous vasodilation was also restored with the local infusion of both apocynin (P < 0.01) and Tempol (P < 0.05) on the HS diet. Nitrotyrosine expression was increased on the HS diet compared with LS (P < 0.05). These findings provide direct evidence of dietary sodium-induced endothelial cell oxidative stress and suggest that NADPH-derived reactive oxygen species contribute to sodium-induced declines in microvascular function. [ABSTRACT FROM AUTHOR]

The skin is an accessible model circulation for studying vascular function and dysfunction across the lifespan. Age-related changes, as well as those associated with disease progression, often appear first in the cutaneous circulation. Furthermore, impaired vascular signaling and attendant endothelial dysfunction, the earliest indicators of cardiovascular pathogenesis, occur in a similar fashion across multiple tissue beds throughout the body, including the skin. Because microvascular dysfunction is a better predictor of long-term outcomes and adverse cardiovascular events than is large vessel disease, an understanding of age-associated changes in the control of the human cutaneous microcirculation is important. This review focuses on 1) the merits of using skin-specific methods and techniques to study vascular function, 2) microvascular changes in aged skin (in particular, the role of the endothelial-derived dilator nitric oxide), and 3) the impact of aging on heat-induced changes in skin vasodilation. While skin blood flow is controlled by multiple, often redundant, mechanisms, our laboratory has used a variety of distinct thermal provocations of this model circulation to isolate specific age-associated changes in vascular function. Skinspecific approaches and techniques, such as intradermal microdialysis coupled with laser-Doppler flowmetry (in vivo) and biochemical analyses of skin biopsy samples (in vitro), have allowed for the targeted pharmacodissection of the mechanistic pathways controlling skin vasoreactivity and study of the impact of aging and disease states. Aged skin has an attenuated ability to vasodilate in response to warm stimuli and to vasoconstrict in response to cold stimuli. [ABSTRACT FROM AUTHOR]

Many studies have reported that there are changes in sympathetic activity throughout the menstrual cycle as there are oestrogen receptor in the hypothalamus and all other parts of the sympathetic nervous system. The purpose of this study was to see whether there were variations in sympathetic activity, skin vasomotor and sweat gland sudomotor rhythms during the menstrual cycle. Eight young female subjects with a regular menstrual cycle participated in the study. Subjects were tested once during the follicular phase and once during the luteal phase. Skin blood flow and sweat rate were significantly higher in the luteal phase compared with the follicular phase (p < .05), but the frequency and magnitude of sudomotor and vasomotor rhythms were significantly greater in the follicular phase (p < .05). In contrast, spectral data showed less sympathetic activity in the luteal phase. A significant finding here is that the sudomotor rhythm of sweat glands is altered by the menstrual cycle. [ABSTRACT FROM AUTHOR]

We recently showed the varying roles of Ca2+-activated (KCa), ATP-sensitive (KATP), and voltage-gated (KV) K+ channels in regulating cholinergic cutaneous vasodilation and sweating in normothermic conditions. However, it is unclear whether the respective contributions of these K+ channels remain intact during dynamic exercise in the heat. Eleven young (23 ± 4 yr) men completed a 30-min exercise bout at a fixed rate of metabolic heat production (400 W) followed by a 40-min recovery period in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and local sweat rate were assessed at four forearm skin sites perfused via intradermal microdialysis with: 1) lactated Ringer solution (control); 2) 50 mM tetraethylammonium (nonspecific KCa channel blocker); 3) 5 mM glybenclamide (selective KATP channel blocker); or 4) 10 mM 4-aminopyridine (nonspecific KV channel blocker). Responses were compared at baseline and at 10-min intervals during and following exercise. KCa channel inhibition resulted in greater CVC versus control at end exercise (P = 0.04) and 10 and 20 min into recovery (both P < 0.01). KATP channel blockade attenuated CVC compared with control during baseline (P = 0.04), exercise (all P ≤ 0.04), and 10 min into recovery (P = 0.02). No differences in CVC were observed with KV channel inhibition during baseline (P = 0.15), exercise (all P ≥ 0.06), or recovery (all P ≥ 0.14). With the exception of KV channel inhibition augmenting sweating during baseline (P = 0.04), responses were similar to control with all K+ channel blockers during each time period (all P ≥ 0.07). We demonstrated that KCa and KATP channels contribute to the regulation of cutaneous vasodilation during rest and/or exercise and recovery in the heat. [ABSTRACT FROM AUTHOR]

It is unclear whether men with low body fat (LO-BF) have impaired thermoregulation during exercise heat stress compared with those with high body fat (HI-BF) when euhydration (EU) is maintained. Furthermore, in LO-BF individuals, hypohydration (HY) impairs thermoregulatory responses during exercise heat stress, but it is unknown whether this occurs in HI-BF counterparts. The purpose of this study was to test the hypotheses that men with HI-BF have impaired thermoregulatory responses to exercise heat stress and that HY further exacerbates these impairments vs. LO-BF. Men with LO-BF [n = 11, body mass (BM) 73.9 ± 8.5 kg, BF% 13.6 ± 3.8] and HI-BF (n = 9, BM 89.6 ± 6.9 kg, BF% 30.2 ± 4.1), in a randomized crossover design, performed 60 min of upright cycling in a hot environment (40.3 ± 0.4°C, relative humidity 32.5 ± 1.9%) at a metabolic heat production rate of 6 W/kg BM and finished exercise either euhydrated (EU; 0.3 ± 1.2 vs. 0.3 ± 0.9% BM loss) or HY (-2.5 ± 1.1 vs. -1.7 ± 1.5% BM loss). Changes in rectal temperature (ΔTrec), local sweat rate (ΔLSR), and cutaneous vascular conductance (ΔCVC; %max) were measured throughout. When EU, LO-BF and HI-BF had similar CVC and LSR responses (P > 0.05); however, LO-BF had a lower ΔTrec vs. HI-BF (0.92 ± 0.35 vs. 1.31 ± 0.3°C, P > 0.021). Compared with EU, HY increased end-exercise ΔTrec in LO-BF (0.47 ± 0.37°C, P > 0.01) but not in HI-BF (-0.06 ± 0.29°C, P > 0.05). HY, compared with EU, did not affect ΔLSR and ΔCVC in either group (P > 0.05). We conclude that, when euhydrated, men with HI-BF have a greater increase in Trec vs. LO-BF but similar CVC and LSR. HY exacerbates increases in Trec in LO-BF but not HI-BF. [ABSTRACT FROM AUTHOR]

The thermoregulatory system interacts vitally with the body fluid regulatory system. Thermoregulatory response during heat stress, such as sweating and cutaneous vasodilation, stimulates body fluid regulatory response by elevating plasma osmolality and reducing central blood volume. Isotonic hypovolemia, or baroreceptor unloading, and plasma hyperosmolality, in turn, inhibit thermoregulatory response to heat stress, suggesting that body fluid regulation is given priority over thermoregulation. On the other hand, osmoregulatory vasopressin secretion and thirst are augmented by elevated body core temperature. Heat acclimation enhances thermoregulatory response to heat stress. Adaptation of the body fluid regulatory system, such as increased plasma volume and reduced osmotic inhibition of thermoregulatory response, is possibly involved in the mechanism for the enhancement of thermoregulatory response to heat stress by heat acclimation. In this review, we discuss the interaction between body fluid regulation, especially osmoregulation, and thermoregulation mainly in humans.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang and Hurr.)

Control of cutaneous circulation is critically important to maintain thermoregulation, especially in individuals with cervical spinal cord injury (CSCI) who have no or less central thermoregulatory drive. However, the peripheral vasoconstrictor mechanism and capability have not been fully investigated after CSCI. Post- and presynaptic sensitivities of the cutaneous vasoconstrictor system were investigated in 8 CSCI and 7 sedentary able-bodied (AB) men using an intradermal microdialysis technique. Eight doses of norepinephrine (NE, 10 -8 to 10 -1 M) and five doses of tyramine (TY, 10 -8 , 10 -5 to 10 -2 M) were administered into the anterior right and left thigh, respectively. Endogenous catecholamines, noradrenaline, and dopamine, collected at the TY site, were determined by high-performance liquid chromatography with electrochemical detection. Regardless of vasoconstrictor agents, cutaneous vascular conductance decreased dose-dependently and responsiveness was similar between the groups (NE: Group P = 0.255, Dose P = 0.014; TY: Group P = 0.468, Dose P < 0.001), whereas the highest dose of each drug induced cutaneous vasodilation. Administration of TY promoted the release of noradrenaline and dopamine in both groups. Notably, the amount of noradrenaline released was similar between the groups ( P = 0.819), although the concentration of dopamine was significantly greater in individuals with CSCI than in AB individuals ( P = 0.004). These results suggest that both vasoconstrictor responsiveness and neural functions are maintained after CSCI, and dopamine in the skin is likely to induce cutaneous vasodilation.

During supine passive heating, increases in skin blood flow (SkBF) and cardiac output (Qc) are both blunted in older adults. The aim here was to determine the effect of acutely correcting the peripheral vasodilatory capacity of aged skin on the integrated cardiovascular responses to passive heating. A secondary aim was to examine the SkBF-Qc relation during hyperthermia in the presence (upright posture) and absence (dynamic exercise) of challenges to central venous pressure. We hypothesized that greater increases in SkBF would be accompanied by greater increases in Qc. Eleven healthy older adults (69 ±3 yr) underwent supine passive heating (0.8°C rise in core temperature; water-perfused suit) after ingesting sapropterin (BH4, a nitric oxide synthase cofactor; 10 mg/kg) or placebo (randomized double-blind crossover design). Twelve young (24 ±1 yr) subjects served as a comparison group. SkBF (laser-Doppler flowmetry) and Qc (open-circuit acetylene washin) were measured during supine heating, heating + upright posture, and heating + dynamic exercise. Throughout supine and upright heating, sapropterin fully restored the SkBF response of older adults to that of young adults but Qc remained blunted. During heat + upright posture, SkBF failed to decrease in untreated older subjects. There were no age- or treatment-related differences in SkBF-Qc during dynamic exercise. The principal finding of this study was that the blunted Qc response to passive heat stress is directly related to age as opposed to the blunted peripheral vasodilatory capacity of aged skin. Furthermore, peripheral impairments to SkBF in the aged may contribute to inapposite responses during challenges to central venous pressure during hyperthermia. [ABSTRACT FROM AUTHOR]

Purpose: We examined whether plasma hyperosmolality induced by oral monosaccharide intake attenuated thermoregulatory responses and whether the responses were different between fructose and glucose. Methods: Ten healthy young subjects performed three trials in a sitting position in an artificial climate chamber (ambient temperature, 28°C; relative humidity, 40%). After resting for 10 min, the subjects drank 300 mL of water alone (control), or 300 mL of water supplemented with 75 g fructose or 75 g glucose. Twenty minutes later, they were heated passively by immersing the lower legs in water at 42°C for 60 min. Plasma osmolality (Posm), sodium ([Na+]p) and insulin concentrations ([Ins]p), and percent change in plasma volume (%△PV) were measured, and esophageal temperature (Tes) thresholds for cutaneous vasodilation (THcvc) and sweating (THSR) at the forearm were determined. Results: Posm was significantly increased by fructose and glucose intake compared with water alone, although %△PV and [Na+]p were not significantly different among the three trials. [Ins]p was significantly higher after glucose intake than after fructose or water alone. THCVC and THSR were significantly higher after fructose intake than after glucose intake, which showed similar values to water intake. Conclusions: These results suggest that the Tes threshold for thermoregulation is elevated after fructose intake, indicating the attenuation of thermoregulatory responses, whereas it is not attenuated after glucose intake. These results provide a novel insight to better determine the carbohydrate component of oral rehydration fluids for preventing dehydration and/or heat disorders. [ABSTRACT FROM AUTHOR]

Oxidative stress promotes vascular dysfunction in chronic kidney disease (CKD). We utilized the cutaneous circulation to test the hypothesis that reactive oxygen species derived from NADPH oxidase and xanthine oxidase impair nitric oxide (NO)-dependent cutaneous vasodilation in CKD. Twenty subjects, 10 stage 3 and 4 patients with CKD (61 ± 4 yr; 5 men/5 women; eGFR: 39 ± 4 ml·min-1·1.73 m-2) and 10 healthy controls (55 ± 2 yr; 4 men/6 women; eGFR: >60 ml.min-1·1.73 m-2) were instrumented with 4 intradermal microdialysis fibers for the delivery of 1) Ringer solution (Control), 2) 10 μM tempol (scavenge superoxide), 3) 100 μM apocynin (NAD(P)H oxidase inhibition), and 4) 10 μM allopurinol (xanthine oxidase inhibition). Skin blood flow was measured via laser-Doppler flowmetry during standardized local heating (42°C). Ng-nitro-L-arginine methyl ester (L-NAME; 10 mM) was infused to quantify the NO-dependent portion of the response. Cutaneous vascular conductance (CVC) was calculated as a percentage of the maximum CVC achieved during sodium nitroprusside infusion at 43°C. Cutaneous vasodilation was attenuated in patients with CKD (77 ± 3 vs. 88 ± 3%, P = 0.01), but augmented with tempol and apocynin (tempol: 88 ± 2 (P = 0.03), apocynin: 91 ± 2% (P = 0.001). The NO-dependent portion of the response was reduced in patients with CKD (41 ± 4 vs. 58 ± 2%, P = 0.04), but improved with tempol and apocynin (tempol: 58 ± 3 (P = 0.03), apocynin: 58 ± 4% (P = 0.03). Inhibition of xanthine oxidase did not alter cutaneous vasodilation in either group (P > 0.05). These data suggest that NAD(P)H oxidase is a source of reactive oxygen species and contributes to microvascular dysfunction in patients with CKD. [ABSTRACT FROM AUTHOR]

Clinical reports have suggested that patients with heart diseases may be particularly vulnerable to heat injury. This review examines the effects of heat stress on cardiovascular and autonomic functions in patients with chronic heart failure (CHF). Laboratory investigations have shown that cutaneous vasodilator responses to heating are impaired in patients, whereas activation of skin sympathetic nerve activation is not attenuated in CHF as compared to controls. Attenuated cutaneous vasodilation may increase the risk of a heat related illness when CHF subjects are exposed to hyperthermic conditions. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Zhang, Wang and Hurr.)

Cutaneous vasodilation associated with whole-body heat stress occurs via withdrawal of adrenergic vasoconstriction and engagement of cholinergic "active" vasodilation, the latter of which attenuates cutaneous vasoconstrictor responsiveness. However, the precise neurotransmitter(s) responsible for this sympatholytic-like effect remain unknown. In skeletal muscle, ATP inhibits adrenergically mediated vasoconstriction. ATP also may be responsible for attenuating cutaneous vasoconstriction since it is coreleased from cholinergic neurons. The effect of ATP on cutaneous vasoconstrictor responsiveness, however, has not been investigated. Accordingly, this study tested the hypothesis that ATP inhibits adrenergically mediated cutaneous vasoconstriction. To accomplish this objective, four microdialysis probes were inserted in dorsal forearm skin of II healthy individuals (mean ± SD; 35 ± 11 years). Local temperature at each site was clamped at 34°C throughout the protocol. Skin blood flow was indexed by laser-Doppler flowmetry and was used to calculate cutaneous vascular conductance (CVC; laser-Doppler-derived flux/mean arterial pressure), which was normalized to peak CVC achieved with sodium nitroprusside infusion combined with local skin heating to ∼42°C. Two membranes were perfused with 30 mM ATP, while the other two membranes were flow matched via administration of 2.8 mM adenosine to serve as control sites. After achieving stable baselines, 1 × 10-4 M tyramine was administered at all sites, while ATP and adenosine continued to be infused at their respective sites. ATP and adenosine infusion increased CVC from baseline by 35 ± 26% CVCpeak units and by 36 ± 15% CVCpeak units, respectively (P = 0.75). Tyramine decreased CVC similarly (by about one-third) at all sites (P < 0.001 for main effect and P = 0.32 for interaction). These findings indicate that unlike in skeletal muscle, ATP does not attenuate tyramine-stimulated vasoconstriction in human skin. [ABSTRACT FROM AUTHOR]

Various aspects of skin blood flow (SkBF) in human beings have been studied experimentally for more than seven decades. While reasonably complete phenomenological descriptions of individual factors have emerged from those investigations, little effort has been devoted to assembling the component parts into a coherent description of the entire system. This paper describes an effort to do that. Although the result is essentially a mathematical model of human SkBF, the model is firmly based on empirical data and not merely an abstract theoretical construct. We found that experimental data for human forearm blood flow (FBF) from many sources are well represented by an equation in which the rate of cutaneous blood flow ( q s) is defined by the equation q s = q s,r AVD × CVCM × CVCL × CVCE. The coefficient q s,r is the perfusion rate at a reference state, and the four component factors are defined as follows: AVD defines centrally mediated active vasodilation as a function of central temperature ( T c), mean skin temperature $$({\bar{T}}_{{\rm s}}),$$ and intensity of exercise $$({\dot{V}}_{{\rm O}_2});$$ CVCM defines reflexly mediated cutaneous vasoconstriction as a function of $${\bar{T}}_{{\rm s}};$$ CVCL defines locally mediated cutaneous vasoconstriction as a function of local skin temperature ( T s); and CVCE defines the effect of exercise on cutaneous vasoconstriction and mean arterial pressure. The definition of each component function is based on experimental data. Two conclusions are particularly significant. One is that the study provides a rational explanation, based on the role of $${\bar{T}}_{{\rm s}},$$ for previously disparate opinions about the non-thermal effect of exercise on active cutaneous vasodilation. The other is that it establishes that the four factors combine multiplicatively, and not additively, as previous investigators have suggested. [ABSTRACT FROM AUTHOR]

Under conditions of heat stress and hyperosmotic dehydration, both animals and humans reduce thermoregulatory evaporation and regulate deep body temperature at elevated levels. Regarding the mechanisms, the main role in producing these thermoregulatory changes during dehydration is attributed to the increased osmolality of body fluids, although the role of the decreased plasma volume without changes in plasma osmolality (hypovolemia/isosmotic dehydration) has not been so far investigated. There are also controversial experimental results regarding the effects of dehydration on heat stress-induced cutaneous vasodilation. Therefore, this paper studied the effects of hypovolemia/isosmotic dehydration on cardiorespiratory responses to hyperthermia and its physical treatment in 17 anaesthetized adult rabbits. The animals were divided into two groups: normovolemic group (NV; n &ThickSpace;=&ThickSpace;10) and hypovolemic group (HV; n &ThickSpace;=&ThickSpace;7). In the HV group, hypovolemia/isosmotic dehydration (decrease in plasma volume by 16.1&ThickSpace;±&ThickSpace;1.2%) was induced by furosemide (5&ThickSpace;mg&ThickSpace;kg -1 i.v.) without change in measured plasma Na + concentration. Hyperthermia (the rise in body temperature (BT) to 42°C by a gradual body surface heating) caused significant increase in minute ventilation ( V E ) in both groups. However, V E values were significantly higher in the HV rabbits compared to the NV animals despite the lower breathing frequency ( p &ThickSpace; [ABSTRACT FROM AUTHOR]

Bright light (BL) exposure at night leads to suppressed secretion of melatonin and an attenuated fall in internal temperature at rest from the night to the early morning. However, it is unknown at the present whether typical diurnal variations in reflex responses to thermal challenges are similarly affected by BL exposure at night. We investigated the control of cutaneous vasodilator and sweating responses to hyperthermia in the early morning after artificial BL exposure at night, compare with dim light (DL) exposure. Six subjects stayed awake in a semi-supine position under DL (120 lx) or BL (2800 lx) conditions between 21.00 and 04.30 h. Urine samples were collected at 04.30 h. Beginning at 05.30 h, the lower legs were immersed for 50 min in 42 degrees C water. The subjects remained awake for 21 h until the end of hot water immersion. Urinary 6-sulphatoxymelatonin levels following BL were significantly lower than after DL. Oesophageal temperature (T es) before heating was significantly higher following BL [36.41+/-0.10 (DL) vs. 36.55+/-0.09 (BL) degrees C]. The T es thresholds for the onset of cutaneous vasodilation and sweating were significantly higher with BL than with DL conditions (approximately 0.15 degrees C, respectively). We found that the internal temperature threshold for thermoregulatory control of cutaneous vasodilation and sweating responses to passive heating in the early morning can be modified by the level of light exposure the prior night. Thus both basal internal temperature and the regulation of internal temperature are modified by BL exposure at night. [ABSTRACT FROM AUTHOR]

To examine the effects of physical training on cutaneous vasodilation and sweating responses of young women in the follicular and luteal phase, 11 physically trained (T group) and 13 untrained (U group) women were passively heated by lower-leg immersion into hot water of 42°C (ambient temperature of 30°C and 45%RH) for 60 min in their mid-follicular and mid-luteal phases of the menstrual cycle. Female hormones increased significantly from the mid-follicular to the mid-luteal phase in T and U groups, but the degree of increase was significantly lower in T group. Mean body temperature $$(\bar{T}_{\rm b})$$ thresholds for cutaneous vasodilation and sweating responses were significantly lower in T group than in U group, in both the menstrual phases, and the differences between the groups were greatest during the mid-luteal phase. The slope of the relationship between frequency of sweat expulsion ( Fsw) and $$\bar{T}_{\rm b}, $$ and between local sweating rate and Fsw was significantly greater in T group, although the slope of the relationship between cutaneous blood flow and $$\bar{T}_{\rm b}$$ did not differ between the groups, regardless of body site or menstrual phase. These results suggest that regular physical activity enhanced sweating and cutaneous vasodilation in young women. The enhancement of sweating was due to both central and peripheral mechanisms, and the enhancement of cutaneous vasodilation was possibly due to a central mechanism. Enhancement of heat loss responses via central mechanisms was greater during the mid-luteal phase than in the mid-follicular phase because the elevation of female reproductive hormone levels during the mid-luteal phase was relatively low in T group. [ABSTRACT FROM AUTHOR]

To examine sex- and menstrual cycle-related differences in thermoregulatory responses to heat exposure, ten young women and six young men were heated passively by immersing their legs in water heated to 42°C for 60 min (in ambient conditions of 30°C and 45% relative humidity). The women underwent heat exposure during the mid-follicular (F) and mid-luteal (L) phases of the menstrual cycle, which were confirmed by assaying plasma female reproductive hormones. The rectal and mean bodytemperatures of women in the L phase were significantly greater than those of women in the F phase and of men during a pre-heating equilibration period (28°C) and during heat exposure. During heat exposure, the local sweat rates () on the forehead, chest, back, and forearm of women in either phase were significantly lower than those of men, but the thighwas similar to that of men. Thedid not change at any site during the different phases of the menstrual cycle. The cutaneous blood flow (%LDF) was significantly greater on the thigh for women in either phase compared with men, but no difference was found at any other site (forehead, chest, back, and forearm). The %LDF on the back was significantly greater for women in the L phase than in the F phase, but those at other sites were similar in both phases. We conclude that, compared with men, heat loss from women depends more on cutaneous vasodilation (especially on the thigh) than on sweating, irrespective of the phase of the menstrual cycle. This phenomenon was due to peripheral mechanisms, as reflected in the greater slope of the relationship between %LDF andlower slope of the relationship betweenand frequency of sweat expulsion, and lower sweat output per gland. The menstrual cycle modified thethreshold for vasodilation and sweat onset in women. Therefore, the sex difference in thethreshold was more marked for women during the L phase than during the F phase. Moreover, the menstrual cycle modified the slope of the relationship between %LDF on the back and [ABSTRACT FROM AUTHOR]