In vivo assessments of microneedle arrays and iontophoresis of pilocarpine in human palmar sweating.

Emotional stress-induced sweating in glabrous skin of the palm and sole, which can be excessive in some individuals (hyperhidrosis), can negatively impact quality of life. Understanding the mechanisms underlying this response can lead to potential treatments. Transdermal iontophoresis is a method to administer ionized sudorific agents to sweat glands within the dermis. However, due to the reduced permeability of pharmacological agents in thicker skin such as the palms, this technique has been shown to be less effective when applied in thicker skin. Thus, we assessed the effectiveness of pre-treating palmar skin with microneedles to create micropores on the stratum corneum of the palm to enhance the iontophoretic delivery of pilocarpine to modulate sweat production. On three separate sessions, we applied microneedles (0.78 cm2, 190 needles with a length of 875 µm) to palm and forearm skin sites. Upon removal of the microneedles, we assessed the number of perforations colored by gentian violet in the forearm only (Protocol 1, n = 20), skin barrier function indexed by transepidermal water loss (TEWL) (Protocol 2, n = 21), and sweating induced by the iontophoretic application of 1% pilocarpine (Protocol 3, n = 43). Briefly, we measured 1) ∼172 dyed spots on forearm skin, 2) an increase of ∼300% and âˆ¼ 900% in TEWL on palm and forearm skin, respectively; and 3) a 2-fold increase in sweating on the palm only following the application of the microneedles. Notably, the microneedle array failed to enhance pilocarpine delivery at either the palm or forearm skin sites. We showed the application of a microneedle array enhanced skin permeability and sweat production on the palm without a concomitant increase in pilocarpine delivery. Therefore, this methodology could be employed to advance our understanding of the causes and treatments of medical conditions such as hyperhidrosis.

Induction and decay of seasonal acclimatization on whole body heat loss responses during exercise in a hot humid environment with different air velocities.

Whether whole body heat loss and thermoregulatory function (local sweat rate and skin blood flow) are different between summer and autumn and between autumn and winter seasons during exercise with different air flow in humid heat remain unknown. We therefore tested the hypotheses that whole body sweat rate (WBSR), evaporated sweat rate, and thermoregulatory function during cycling exercise in autumn would be higher than in winter but would be lower than in summer under hot-humid environment (32 C, 75% RH). We also tested the hypothesis that the increase of air velocity would enhance evaporated sweat rate and sweating efficiency across winter, summer, and autumn seasons. Eight males cycled for 1 h at 40% V̇o2max in winter, summer, and autumn seasons. Using an electric fan, air velocity increased from 0.2 m/s to 1.1 m/s during the final 20 min of cycling. The autumn season resulted in a lower WBSR, unevaporated sweat rate, and a higher sweating efficiency compared with summer (all P ≤ 0.05) but WBSR and unevaporated sweat rate in autumn were higher than in winter and thus sweating efficiency was lower when compared with winter only at the air velocity of 0.2 m/s (All P ≤ 0.05). Furthermore, evaporated sweat rate and core temperature (Tcore) were not different among winter, summer, and autumn seasons (All P > 0.19). In conclusion, changes in WBSR across different seasons do not alter Tcore during exercise in a hot humid environment. Furthermore, increasing air velocity enhances evaporated sweat rate and sweating efficiency across all seasons.

Effects of tetraethylammonium-sensitive K+ channel blockade on cholinergic and thermal sweating in endurance-trained and untrained men.

NEW FINDINGS: What is the central question of this study? Does inhibition of K+ channels modulate the exercise-training-induced augmentation in cholinergic and thermal sweating? What is the main finding and its importance? Iontophoretic administration of tetraethylammonium, a K+ channel blocker, blunted sweating induced by a low dose (0.001%) of the cholinergic agent pilocarpine, but not heat-induced sweating. However, no differences in the cholinergic sweating were observed between young endurance-trained and untrained men. Thus, while K+ channels play a role in the regulation of eccrine sweating, they do not contribute to the increase in sweating commonly observed in endurance-trained adults. Our findings provide important new insights into the mechanisms underlying the regulation of sweating by endurance conditioning. ABSTRACT: We evaluated the hypothesis that the activation of K+ channels mediates the exercise-training-induced augmentation of cholinergic and thermal sweating. On separate days, 11 endurance-trained and 10 untrained men participated in two experimental protocols. Prior to each protocol, we administered 2% tetraethylammonium (TEA, K+ channels blocker) and saline (Control) at forearm skin sites on both arms via transdermal iontophoresis. In protocol 1, low (0.001%) and high (1%) doses of pilocarpine were administered at the TEA-treated and Control sites over a 60-min period. In protocol 2, participants were passively heated by immersing their lower limbs in hot water (43°C) until core (rectal) temperature (Tc ) increased by 0.8°C above resting levels. Administration of TEA attenuated cholinergic sweating (P = 0.001) during the initial 20 min after the treatment of low dose of pilocarpine only whilst the response was similar between the groups (P = 0.163). Cholinergic and thermal sweating were higher in the trained relative to the untrained men (all P ≤ 0.033). Thermal sweating reached ∼90% of the response at a Tc elevation of 0.8°C during the initial 20 min of passive heating, which corresponds to the period wherein TEA attenuated cholinergic sweating in protocol 1. However, sweating did not differ between the Control and TEA sites in either group (P = 0.704). We showed that activation of K+ channels does not appear to mediate the elevated sweating response induced by a low dose of pilocarpine in trained men. We also demonstrated that K+ channels do not contribute to sweating during heat stress in either group.

Influence of exercise intensity and regional differences in the sudomotor recruitment pattern in exercising prepubertal boys and young men.

We investigated the influence of exercise intensities and regional differences in the sudomotor recruitment pattern in boys. Six prepubertal boys (age 11 ± 1 yr) cycled at light, moderate, and high exercise intensity (35%, 50%, and 65% VO2max) for 30 min in a temperate condition (28 °C, 40% relative humidity). Local sweat rate (ventilated capsule) and number of activated sweat glands (starch-iodine technique) at five body sites were assessed and sweat gland output was calculated. Responses in boys were compared with those in nine young men (23 ± 1 yr) tested under identical conditions. The forehead, chest, back, and forearm, but not thigh, sweat rate increased from light to moderate and at high intensities in boys (all p ≤ 0.005) but not from moderate to high (all p ≥ 0.071). The sweat rate on the forehead was relatively higher (p ≤ 0.045) and thigh was lower (p ≤ 0.050) than other sites in boys at moderate and high intensities. Exercise intensity-dependent sweating was associated with activating more sweat glands but not increasing glandular output in boys. The sweat rate in boys was attenuated versus men heterogeneously across body sites concurrent to low glandular outputs (all p ≤ 0.027). We conclude that exercise intensity modulates the sweat rate in boys by changing the number of activated sweat glands heterogeneously among skin sites. Age-related differences in the sudomotor pattern are evident at higher exercise intensities. Development of glandular output per gland occurring from boys to young men may play a key role in modulating sweat rate with respect to exercise intensity and regional differences.

The effect of seasonal acclimatization on whole body heat loss response during exercise in a hot humid environment with different air velocity.

Seasonal acclimatization from winter to summer is known to enhance thermoeffector responses in hot-dry environments during exercise whereas its impact on sweat evaporation and core temperature (Tcore) responses in hot-humid environments remains unknown. We, therefore, sought to determine whether seasonal acclimatization is able to modulate whole body sweat rate (WBSR), evaporated sweat rate, sweating efficiency, and thermoregulatory function during cycling exercise in a hot-humid environment (32°C, 75% RH). We also determined whether the increase in air velocity could enhance evaporated sweat rate and sweating efficiency before and after seasonal acclimatization. Twelve males cycled for 1 h at 40% V̇o2max in winter (preacclimatization) and repeated the trial again in summer (after acclimatization). For the last 20 min of cycling at a steady-state of Tcore, air velocity increased from 0.2 (0.04) m/s to 1.1 (0.02) m/s by using an electric fan located in front of the participant. Seasonal acclimatization enhanced WBSR, unevaporated sweat rate, local sweat rate and mean skin temperature compared with preacclimatization state (all P < 0.05) whereas sweating efficiency was lower (P < 0.01) until 55 min of exercise. Tcore and evaporated sweat rate were unaltered by acclimatization status (all P > 0.70). In conclusion, seasonal acclimatization enhances thermoeffector responses but does not attenuate Tcore during exercise in a hot-humid environment. Furthermore, increasing air velocity enhances evaporated sweat rate and sweating efficiency irrespective of acclimated state. NEW & NOTEWORTHY Seasonal acclimatization to humid heat enhances eccrine sweat gland function and thus results in a higher local and whole body sweat rate but does not attenuate Tcore during exercise in a hot-humid environment. Sweating efficiency is lower after seasonal acclimatization to humid heat compared with preacclimatization with and without the increase of air velocity. However, having a lower sweating efficiency does not mitigate the Tcore response during exercise in a hot-humid environment.

Physical activities and surgical outcomes in elderly patients with acute type A aortic dissection.

OBJECTIVE: Although elderly patients undergoing surgery for acute type A aortic dissection (ATAAD) is increasing, their physical activities are not fully understood. We report the physical activities and surgical outcomes in elderly patients who underwent ATAAD. METHODS: From 2009 to 2019, 103 consecutive patients underwent surgery for ATAAD at our institution. Surgical outcomes along with pre- and postoperative physical activities in 52 elderly patients (≥70 years old) were compared with those in 51 younger patients (<70 years old). Postoperative walking difficulty was defined as taking ≥30 days to regain the ability to walk 200 m postoperatively or as the inability to walk at discharge. RESULTS: It took longer for elderly patients to regain the ability to walk 100 or 200 m postoperatively. ROC analysis revealed the AUC of the duration for walking 200 m postoperatively as a prognostic indicator for late deaths was 0.878, with the highest accuracy at 30 days (sensitivity = 83.3%, specificity = 91.8%). Hospital mortality within 30 days was 3.8%, and 1-, 3-, and 5-years survival rates were 92%, 84.7%, 84.7%, respectively, for elderly patients, with no significant differences between groups. Cox proportional hazard analysis showed postoperative walking difficulty was an independent risk factor for late mortality in all cohorts (p = .017). CONCLUSIONS: Elderly patients undergoing surgical ATAAD repair showed acceptable surgical outcomes. However, they were more likely to decrease their physical activities postoperatively. Postoperative difficulty in walking was an independent risk factor for the late mortality in patients with ATAAD.

The sweat glands' maximum ion reabsorption rates following heat acclimation in healthy older adults.

NEW FINDINGS: What is the central question to this study? Do the sweat glands' maximum ion reabsorption rates increase following heat acclimation in healthy older individuals and is this associated with elevated aldosterone concentrations? What is the main finding and its importance? Sweat gland maximum ion reabsorption rates improved heterogeneously across body sites, which occurred without any changes in aldosterone concentration following a controlled hyperthermic heat acclimation protocol in healthy older individuals. ABSTRACT: We examined whether the eccrine sweat glands' ion reabsorption rates improved following heat acclimation (HA) in older individuals. Ten healthy older adults (>65 years) completed a controlled hyperthermic (+0.9°C rectal temperature, Tre ) HA protocol for nine non-consecutive days. Participants completed a passive heat stress test (lower leg 42°C water submersion) pre-HA and post-HA to assess physiological regulation of sweat gland ion reabsorption at the chest, forearm and thigh. The maximum ion reabsorption rate was defined as the inflection point in the slope of the relation between galvanic skin conductance and sweat rate (SR). We explored the responses again after a 7-day decay. During passive heating, the Tb thresholds for sweat onset on the chest and forearm were lowered after HA (P < 0.05). However, sweat sensitivity (i.e. the slope), the SR at a given Tre and gross sweat loss did not improve after HA (P > 0.05). Any changes observed were lost during the decay. Pilocarpine-induced sudomotor responses to iontophoresis did not change after HA (P ≥ 0.801). Maximum ion reabsorption rate was only enhanced at the chest (P = 0.001) despite unaltered aldosterone concentration after HA. The data suggest that this adaptation is lost after 7 days' decay. The HA protocol employed in the present study induced partial adaptive sudomotor responses. Eccrine sweat gland ion reabsorption rates improved heterogeneously across the skin sites. It is likely that aldosterone secretion did not alter the chest sweat ion reabsorption rates observed in the older adults.

The relative contribution of α- and ß-adrenergic sweating during heat exposure and the influence of sex and training status.

While human eccrine sweat glands respond to adrenergic agonists, there remains a paucity of information on the factors modulating this response. Thus, we assessed the relative contribution of α- and ß-adrenergic sweating during a heat exposure and as a function of individual factors of sex and training status. α- and ß-adrenergic sweating was assessed in forty-eight healthy young men (n = 35) and women (n = 13) including endurance-trained (n = 12) and untrained men (n = 12) under non-heat exposure (temperate, 25°C; n = 17) and heat exposure (hot, 35°C; n = 48) conditions using transdermal iontophoresis of phenylephrine (α-adrenergic agonist) and salbutamol (ß-adrenergic agonist) on the ventral forearm, respectively. Adrenergic sweating was also measured after iontophoretic administration of atropine (muscarinic receptor antagonist) or saline (control) to evaluate how changes in muscarinic receptor activity modulate the adrenergic response to a heat exposure (n = 12). α- and ß-adrenergic sweating was augmented in hot compared with temperate conditions (both P ≤ .014), albeit the relative increase was greater in ß (~5.4-fold)- as compared to α (~1.5-fold)-adrenergic-mediated sweating response. However, both α- and ß-adrenergic sweating was abolished by atropinization (P = .001). Endurance-trained men showed an augmentation in α- (P = .043) but not ß (P = .960)-adrenergic sweating as compared to untrained men. Finally, a greater α- and ß-adrenergic sweating response (both P ≤ .001) was measured in habitually active men than in women. We show that heat exposure augments α-and ß-adrenergic sweating differently via mechanisms associated with altered muscarinic receptor activity. Sex and training status modulate this response.

Effects of L-type voltage-gated Ca2+ channel blockade on cholinergic and thermal sweating in habitually trained and untrained men.

We evaluated the hypothesis that the activation of L-type voltage-gated Ca2+ channels contributes to exercise training-induced augmentation in cholinergic sweating. On separate days, 10 habitually trained and 10 untrained men participated in two experimental protocols. Prior to each protocol, we administered 1% verapamil (Verapamil, L-type voltage-gated Ca2+ channel blocker) and saline (Control) at forearm skin sites on both arms via transdermal iontophoresis. In protocol 1, we administered low (0.001%) and high (1%) doses of pilocarpine at both the verapamil-treated and verapamil-untreated forearm sites. In protocol 2, participants were passively heated by immersing their limbs in hot water (43°C) until rectal temperature increased by 1.0°C above baseline resting levels. Sweat rate at all forearm sites was continuously measured throughout both protocols. Pilocarpine-induced sweating in Control was higher in trained than in untrained men for both the concentrations of pilocarpine (both P ≤ 0.001). Pilocarpine-induced sweating at the low-dose site was attenuated at the Verapamil versus the Control site in both the groups (both P ≤ 0.004), albeit the reduction was greater in trained as compared with in untrained men (P = 0.005). The verapamil-mediated reduction in sweating remained intact at the high-dose pilocarpine site in the untrained men (P = 0.004) but not the trained men (P = 0.180). Sweating did not differ between Control and Verapamil sites with increases in rectal temperature in both groups (interaction, P = 0.571). We show that activation of L-type voltage-gated Ca2+ channels modulates sweat production in habitually trained men induced by a low dose of pilocarpine. However, no effect on sweating was observed during passive heating in either group.

Does the iontophoretic application of bretylium tosylate modulate sweating during exercise in the heat in habitually trained and untrained men?

NEW FINDINGS: What is the central question of this study? Does the administration of the adrenergic presynaptic release inhibitor bretylium tosylate modulate sweating during exercise in the heat, and does this response differ between habitually trained and untrained men? What is the main finding and its importance? Iontophoretic administration of bretylium tosylate attenuates sweating during exercise in the heat in habitually trained and untrained men. However, a greater reduction occurred in trained men. The findings demonstrate a role for cutaneous adrenergic nerves in the regulation of eccrine sweating during exercise in the heat and highlight a need to advance our understanding of neural control of human eccrine sweat gland activity. ABSTRACT: We recently reported an influence of cutaneous adrenergic nerves on eccrine sweat production in habitually trained men performing an incremental exercise bout in non-heat stress conditions. Based on an assumption that increasing heat stress induces cholinergic modulation of sweating, we evaluated the hypothesis that the contribution of cutaneous adrenergic nerves on sweating would be attenuated during exercise in the heat. Twenty young habitually trained and untrained men (n = 10/group) underwent three successive bouts of 15 min of light-, moderate- and vigorous-intensity cycling (equivalent to 30, 50, and 70% of peak oxygen uptake ( V̇O2peak ) respectively), each separated by a 15 min recovery while wearing a perfusion suit perfused with warm water (43°C). Sweat rate (ventilated capsule) was measured continuously at two bilateral forearm skin sites treated with 10 mm bretylium tosylate (an inhibitor of neurotransmitter release from adrenergic nerve terminals) and saline (control) via transdermal iontophoresis. A greater sweat rate was measured during vigorous exercise only in trained as compared to untrained men (P = 0.014). In both groups, sweating was reduced at the bretylium tosylate versus control sites, albeit the magnitude of reduction was greater in the trained men (P ≤ 0.024). These results suggest that cutaneous adrenergic nerves modulate sweating during exercise performed under a whole-body heat stress, albeit a more robust response occurs in trained men. While it is accepted that a cholinergic mechanism plays a primary role in the regulation of sweating during an exercise-heat stress, our findings highlight the need for additional studies aimed at understanding the neural control of human eccrine sweating.

Does α1-adrenergic receptor blockade modulate sweating during incremental exercise in young endurance-trained men?

PURPOSE: Human eccrine sweat glands respond to α1-adrenergic receptor agonists. We recently reported that adrenergic mechanisms contribute to sweating in endurance-trained men during an incremental exercise to volitional fatigue. However, it remains unclear if this response is mediated by α1-adrenergic receptor activation. METHODS: Twelve endurance-trained men performed an incremental cycling bout until exhaustion while wearing a water-perfused suit to clamp skin temperature at ~ 34 °C. Bilateral forearm sweat rates were measured wherein the distal area was treated with either 1% terazosin (α1-adrenergic receptor antagonist) or saline solution on the opposite limb (Control) via transdermal iontophoresis. We also measured proximal bilateral forearm sweat rate in untreated sites to confirm that no between-limb differences in forearm sweat rate occurred. Once sweat rate returned to pre-exercise resting levels at ~ 20 min postexercise, 0.25% phenylephrine (α1-adrenergic receptor agonist) was iontophoretically administered to skin to verify α1-adrenergic receptor blockade. RESULTS: Sweat rates at the proximal untreated right and left forearm sites were similar during exercise (interaction, P = 0.581). Similarly, no effect of terazosin on sweat rate was measured relative to control site (interaction, P = 0.848). Postexercise administration of phenylephrine increased sweat rate at the control site (0.08 ± 0.09 mg cm-2 min-1), which was suppressed by ~ 90% at the terazosin-treated site (0.01 ± 0.02 mg cm-2 min-1) (P = 0.026), confirming that α1-adrenergic receptor blockade was intact. CONCLUSION: Our findings demonstrate that α1-adrenergic receptors located at eccrine sweat glands do not contribute to eccrine sweating during incremental exercise in young endurance-trained men.

Effects of isomaltulose ingestion on postexercise hydration state and heat loss responses in young men.

NEW FINDINGS: What is the central question of this study? What are the effects of isomaltulose, an ingredient in carbohydrate-electrolyte beverages to maintain glycaemia and attenuate the risk of dehydration during exercise heat stress, on postexercise rehydration and physiological heat loss responses? What is the main finding and its importance? Consumption of a 6.5% isomaltulose-electrolyte beverage following exercise heat stress restored hydration following a 2 h recovery as compared to a 2% solution or water only. While the 6.5% isomaltulose-electrolytes increased plasma volume and plasma osmolality, which are known to modulate postexercise heat loss, sweating and cutaneous vascular responses did not differ between conditions. Consequently, ingestion beverages containing 6.5% isomaltulose-electrolytes enhanced postexercise rehydration without affecting heat loss responses. ABSTRACT: Isomaltulose is a disaccharide carbohydrate widely used during exercise to maintain glycaemia and hydration. We investigated the effects of ingesting a beverage containing isomaltulose and electrolytes on postexercise hydration state and physiological heat loss responses. In a randomized, single-blind cross-over design, 10 young healthy men were hypohydrated by performing up to three 30 min successive moderate-intensity (50% heart rate reserve) bouts of cycling, each separated by 10 min, while wearing a water-perfusion suit heated to 45°C. The protocol continued until a 2% reduction in body mass was achieved. Thereafter, participants performed a final 15 min moderate-intensity exercise bout followed by a 2 h recovery. Following cessation of exercise, participants ingested a beverage consisting of (i) water only (Water), (ii) 2% isomaltulose (CHO-2%), or (iii) 6.5% isomaltulose (CHO-6.5%) equal to the volume of 2% body mass loss within the first 30 min of the recovery. Changes in plasma volume (ΔPV) after fluid ingestion were greater for CHO-6.5% compared with CHO-2% (120 min postexercise) and Water (90 and 120 min) (all P ≤ 0.040). Plasma osmolality remained elevated with CHO-6.5% compared with consumption of the other beverages at 30 and 90 min postexercise (all P ≤ 0.050). Urine output tended to be reduced with CHO-6.5% compared to other fluid conditions (main effect, P = 0.069). Rectal and mean skin temperatures, chest sweat rate and cutaneous perfusion did not differ between conditions (all P > 0.05). In conclusion, compared with CHO-2% and Water, consuming a beverage consisting of CHO-6.5% and electrolytes during recovery under heat stress enhances PV recovery without modulating physiological heat loss responses.

ß-Adrenergic receptor blockade does not modify non-thermal sweating during static exercise and following muscle ischemia in habitually trained individuals.

PURPOSE: This study investigated the influence of ß-adrenergic receptor blockade on sweating during bilateral static knee extension (KE) and lateral isometric handgrip (IH) exercises followed by post-exercise muscle ischemia (PEMI) in habitually trained individuals. METHOD: Ten habitually trained men (maximum oxygen uptake, 57.1 ± 3.4 ml kg-1 min-1) were mildly heated by increasing their skin temperature, and bilateral KE or lateral IH exercises at an intensity of 60% maximum voluntary contraction were subsequently performed for 1 min, followed by PEMI to stimulate muscle metaboreceptors for 2 min. Sweat rates were measured on the bilateral forearms (KE) or thighs (IH) transdermally administered with 1% propranolol (propranolol, a non-selective ß-adrenergic receptor inhibitor) or saline (control) via iontophoresis. RESULTS: Relative to the pre-exercise baseline values, IH exercise (P = 0.038) followed by PEMI (P = 0.041) similarly increased sweat rates on the thighs at both control and propranolol sites (baseline, 0.05 ± 0.04 vs. 0.05 ± 0.04; IH, 0.14 ± 0.12 vs. 0.15 ± 0.14; PEMI, 0.14 ± 0.16 vs. 0.14 ± 0.16 mg cm-2 min-1). KE increased sweat rates on the forearms (P = 0.001) at both control and propranolol sites similarly (baseline, 0.02 ± 0.03 vs. 0.02 ± 0.03; KE, 0.21 ± 0.19 vs. 0.20 ± 0.18), whereas PEMI did not significantly induce sweating at these sites (P = 0.260) (0.09 ± 0.12 and 0.10 ± 0.12 mg cm-2 min-1, respectively). CONCLUSION: These results suggest that non-thermal drives induced by static exercise and PEMI do not elicit ß-adrenergic sweating in habitually trained individuals even when the non-thermal drives are originated from leg(s) under the conditions in the present study.

Age-related attenuation of conduit artery blood flow response to passive heating differs between the arm and leg.

PURPOSE: Little is known about why the attenuation of heat loss responses with aging begins in the lower limbs. This study sought to determine whether passive heating causes the age-related decrease and limb-specific difference of blood flow (BF) responses between conduit brachial and femoral arteries, which are related to differences of cutaneous vascular conductance (CVC) between the upper and lower limbs. METHOD: In 15 older and 12 younger males, BF in the brachial and femoral arteries was ultrasonically measured and CVC in the forearm and thigh was assessed during lower leg immersion in hot water at 42 °C (ambient temperature: 30 °C, relative humidity: 45%) for 40 min. RESULTS: The increased BF of brachial artery at the end of passive heating was similar between both age groups (older: 140 ± 4%; younger: 146 ± 11%), while that of femoral artery was smaller in older than younger group (119 ± 4% vs. 166 ± 11%, P < 0.01). Moreover, the increased CVC in the forearm was similar between the age groups (older: 356 ± 50%; younger: 308 ± 46%), although CVC in the thigh was significantly lower in older than younger group (303 ± 33% vs. 427 ± 51%, P < 0.05). These results corresponded to the BF responses of the brachial and femoral arteries, respectively. CONCLUSION: These results indicate that age-related decrease and limb-specific difference occur also in conduit arteries of arm and leg, which might be related to the different reduction in CVC between forearm and thigh.

Cutaneous adrenergic nerve blockade attenuates sweating during incremental exercise in habitually trained men.

It remains unknown whether cutaneous adrenergic nerves functionally contribute to sweat production during exercise. This study examined whether cutaneous adrenergic nerve blockade attenuates sweating during incremental exercise, specifically in habitually trained individuals. Accordingly, 10 habitually trained and 10 untrained males (V̇o2max: 56.7 ± 5.4 and 38.9 ± 6.7 ml·kg-1·min-1, respectively; P < 0.001) performed incremental semirecumbent cycling (20 W/min) until exhaustion. Sweat rates (ventilated capsule) were measured at two bilateral forearm skin sites on which either 10 mM bretylium tosylate (BT) (an inhibitor of neurotransmitter release from sympathetic adrenergic nerve terminals) or saline (Control) was transdermally administered via iontophoresis. BT treatment delayed sweating onset in both groups (∼0.66 min; P = 0.001) and suppressed the sweat rate relative to the Control treatment at ≥70% relative total exercise time in trained individuals (each 10% increment; all P ≤ 0.009) but not in untrained counterparts ( P = 0.122, interaction between relative time × treatment). Changes in total sweat production at the BT site relative to the Control site were greater in trained individuals than in untrained counterparts (area under the curve, -0.86 ± 0.67 and -0.22 ± 0.39 mg/cm2, respectively; P = 0.023). In conclusion, we demonstrated that cutaneous adrenergic nerves do modulate sweating during incremental exercise, which appeared to be more apparent in habitually trained men (e.g., ≥70% maximum workload). Although our results indicated that habitual exercise training may augment neural adrenergic sweat production during incremental exercise, additional studies are required to confirm this possibility. NEW & NOTEWORTHY We demonstrated for the first time that cutaneous adrenergic nerves do modulate sweating during high-intensity exercise in humans (≥70% maximum workload). In addition, neural adrenergic sweating appeared to be greater in habitually trained individuals than in untrained counterparts, although further studies are necessary to confirm such a possibility. Nonetheless, the observations presented herein advance our understanding on human thermoregulation while providing new evidence for the neutral mediation of adrenergic sweating during exercise.

The effects of exercise and passive heating on the sweat glands ion reabsorption rates.

The sweat glands maximum ion reabsorption rates were investigated (n = 12, 21.7 ± 3.0 years, 59.4 ± 9.8 kg, 166.9 ± 10.4 cm and 47.1 ± 7.5 mL/kg/min) during two separate endogenous protocols; cycling at 30% (LEX) and 60% VO2max (MEX) and one exogenous trial; passive heating (PH) (43°C water lower leg immersion) in 27°C, 50%RH. Oesophageal temperature (Tes ), skin temperature (Tsk ), and forearm, chest and lower back sweat rate (SR) and galvanic skin conductance (GSC) were measured. Salivary aldosterone was measured pre-and postheating (n = 3). Using the ∆SR threshold for an increasing ∆GSC to identify maximum sweat ion reabsorption rate revealed higher reabsorption rates during MEX compared to PH (mean of all regions: 0.63 ± 0.28 vs. 0.44 ± 0.3 mg/cm2 /min, P < 0.05). It was not possible to identify the ion reabsorption rate during LEX for some participants. Tes and mean Tsk were different between conditions but mean body temperature (Tb ) and local Tsk (forearm, chest and back) were similar (P > 0.05). Aldosterone increased more during MEX (72.8 ± 36.6 pg/mL) compared to PH (39.2 ± 17.5 pg/mL) and LEX (1.8 ± 9.7 pg/mL). The back had a higher threshold than the forearm (P < 0.05) but it was similar to the chest (P > 0.05) (mean of all conditions; 0.64 ± 0.33, 0.42 ± 0.25, 0.54 ± 0.3 mg/cm2 /min, respectively). Although the differences between conditions may be influenced by thermal or nonthermal mechanism, our results indicate a possibility that the sweat glands maximum ion reabsorption rates may be different between exercise and passive heating without mediating skin regional differences.

Do nitric oxide synthase and cyclooxygenase contribute to sweating response during passive heating in endurance-trained athletes?

The aim of our study was to determine if habitual endurance training can influence the relative contribution of nitric oxide synthase (NOS) and cyclooxygenase (COX) in the regulation of sweating during a passive heat stress in young adults. Ten trained athletes and nine untrained counterparts were passively heated until oral temperature (as estimated by sublingual temperature, Tor) increased by 1.5°C above baseline resting. Forearm sweat rate (ventilated capsule) was measured at three skin sites continuously perfused with either lactated Ringer's solution (Control), 10 mmol/L NG -nitro-L-arginine methyl ester (L-NAME, non-selective NOS inhibitor), or 10 mmol/L ketorolac (Ketorolac, non-selective COX inhibitor) via intradermal microdialysis. Sweat rate was averaged for each 0.3°C increase in Tor Sweat rate at the L-NAME site was lower than Control following a 0.9 and 1.2°C increase in Tor in both groups (all P ≤ 0.05). Relative to the Control site, NOS-inhibition reduced sweating similarly between the groups (P = 0.51). Sweat rate at the Ketorolac site was not different from the Control at any levels of Tor in both groups (P > 0.05). Nevertheless, a greater sweat rate was measured at the end of heating in the trained as compared to the untrained individuals (P ≤ 0.05). We show that NOS contributes similarly to sweating in both trained and untrained individuals during a passive heat stress. Further, no effect of COX on sweating was measured for either group. The greater sweat production observed in endurance-trained athletes is likely mediated by factors other than NOS- and COX-dependent mechanisms.

Evidence for ß-adrenergic modulation of sweating during incremental exercise in habitually trained males.

The aim of the present study was to determine the ß-adrenergic contribution to sweating during incremental exercise in habitually trained males. Nine habitually trained and 11 untrained males performed incremental cycling until exhaustion (20 W/min). Bilateral forearm sweat rates (ventilated capsule) were measured at two skin sites that were transdermally administered via iontophoresis with either 1% propranolol (Propranolol, a nonselective ß-adrenergic receptor antagonist) or saline (Control). The sweat rate was evaluated as a function of both relative (percentage of maximum workload) and absolute exercise intensities. The sweat rate at the Propranolol site was lower than the control during exercise at 80 (0.57 ± 0.21 and 0.45 ± 0.19 mg·cm-2·min-1 for Control and Propranolol, respectively) and 90% (0.74 ± 0.22 and 0.65 ± 0.17 mg·cm-2·min-1, respectively) of maximum workload in trained males (all P < 0.05). By contrast, no between-site differences in sweat rates were observed in untrained counterparts (all P > 0.05). At the same absolute intensity, higher sweat rates on the control site were observed in trained males relative to the untrained during exercise at 160 (0.23 ± 0.20 and 0.04 ± 0.05 mg·cm-2·min-1 for trained and untrained, respectively) and 180 W (0.40 ± 0.20 and 0.13 ± 0.13 mg·cm-2·min-1, respectively) (all P < 0.05), whereas this between-group difference was not observed at the Propranolol site (all P > 0.05). We show that the ß-adrenergic mechanism does modulate sweating during exercise at a submaximal high relative intensity in habitually trained males. The ß-adrenergic mechanism may in part contribute to the greater sweat production in habitually trained males than in untrained counterparts during exercise.NEW & NOTEWORTHY We demonstrated for the first time that the ß-adrenergic mechanism does modulate sweating (i.e., ß-adrenergic sweating) during exercise using a localized ß-adrenoceptor blockade in humans in vivo. ß-Adrenergic sweating was evident in habitually trained individuals during exercise at a submaximal high relative intensity (80-90% maximal work). This observation advances our understanding of human thermoregulation during exercise and of the mechanism that underlies sweat gland adaptation to habitual exercise training.

Maximum rate of sweat ions reabsorption during exercise with regional differences, sex, and exercise training.

PURPOSE: It is recently reported that determining sweat rate (SR) threshold for increasing galvanic skin conductance (GSC) would represent a maximum rate of sweat ion reabsorption in sweat glands. We evaluate the maximum rate of sweat ion reabsorption over skin regions, sex, and long-term exercise training by using the threshold analysis in the present study. METHODS: Ten males (2 untrained, 4 sprinters, and 4 distance runners) and 12 females (5 untrained, 4 sprinters, and 3 distance runners) conducted graded cycling exercise for 45 min at low, middle, and high exercise intensities (heart rate 100-110, 120-130, and 140-150 beats/min, respectively) for 10, 15, and 20 min, respectively, at 30 °C and 50% relative humidity. Comparisons were made between males and females and among untrained individuals, distance runners, and sprinters on the back and forearm. RESULTS: SR threshold for increasing GSC on back was significantly higher than that of forearm (P < 0.05) without any sex differences (back 0.70 ± 0.08 and 0.61 ± 0.04, forearm 0.40 ± 0.05 and 0.45 ± 0.06 mg/cm2/min for males and females, respectively). Distance runners and sprinters showed higher SR threshold for increasing GSC than that of untrained subjects on back (P < 0.05) but not on forearm (back 0.45 ± 0.06, 0.83 ± 0.06, and 0.70 ± 0.04, forearm 0.33 ± 0.04, 0.49 ± 0.02, and 0.39 ± 0.07 mg/cm2/min for untrained subjects, distance runners, and sprinters, respectively). CONCLUSION: These results suggest that the maximum sweat ion reabsorption rate on the back is higher than that of forearm without sex differences. Furthermore, exercise training in distance runners and sprinters improves the maximum sweat ion reabsorption rate on the back.

Sweating responses to isometric hand-grip exercise and forearm muscle metaboreflex in prepubertal children and elderly.

NEW FINDINGS: What is the central question of this study? Non-thermal factors (e.g. muscle metaboreflex) contribute to the sweating response during exercise. Although it is well recognized that the sweating responses caused by core temperature elevation in prepubertal children and the elderly are attenuated compared with young adults, it is unknown whether non-thermal sweating is also attenuated in these populations. What is the main finding and its importance? The non-thermal sweating response during isometric hand-grip exercise and isolated muscle metaboreflex were attenuated in prepubertal children compared with young adults in a non-uniform manner over the body, but only during the muscle metaboreflex in the elderly. This may explain the maturation- and ageing-related decline of sweating during exercise. The purpose of the present study was to investigate sweating responses to isometric hand-grip (IH) exercise and muscle metaboreflex in prepubertal children and the elderly. In hot conditions (ambient temperature, 35°C; relative humidity, 45%), 13 healthy young adults, 10 prepubertal children and 10 elderly subjects (aged 20.4 ± 1.2, 11.4 ± 0.5 and 63.5 ± 3.1 years, respectively) repeated a three hand-grip exercise protocol that consisted of 1 min IH exercise at 15, 30 or 45% of maximal voluntary contraction (MVC) followed by 2 min postexercise forearm occlusion. Local sweat rates (SRs) on the forehead, chest, forearm, thigh and palm were continuously measured (ventilated capsule method). The forehead SR in prepubertal children during IH exercise at 45% MVC was significantly lower than that of young adults (0.26 ± 0.22 and 0.08 ± 0.15 mg cm-2  min-1 for young adults and children, respectively; P < 0.05) but not of the elderly at any exercise intensities. The SR on the chest (0.22 ± 0.22 and -0.01 ± 0.05 mg cm-2  min-1 for young adults and children, respectively), forearm (0.14 ± 0.12 and 0.03 ± 0.04 mg cm-2  min-1 ) and thigh (0.13 ± 0.10 and 0.02 ± 0.03 mg cm-2  min-1 ) during postexercise occlusion at 45% MVC was significantly lower in children than in young adults (P < 0.05). Elderly subjects showed a significantly lower SR on the forearm (0.04 ± 0.04 and 0.01 ± 0.02 mg cm-2  min-1 for young adults and elderly, respectively) and thigh (0.07 ± 0.07 and 0.01 ± 0.03 mg cm-2  min-1 ) at 15% MVC and on the thigh at 45% MVC (0.13 ± 0.10 and 0.04 ± 0.04 mg cm-2  min-1 ) during postexercise occlusion compared with young adults (P < 0.05). These results suggest that sweating responses to IH exercise and muscle metaboreflex were underdeveloped in prepubertal children and that ageing attenuates the response to the muscle metaboreflex in a way that is not consistent across the body.