Do nitric oxide synthase and cyclooxygenase contribute to the heat loss responses in older males exercising in the heat?

This study evaluated the separate and combined roles of nitric oxide synthase (NOS) and cyclooxygenase (COX) in forearm sweating and cutaneous vasodilatation in older adults during intermittent exercise in the heat. Twelve healthy older (62 ± 7 years) males performed two 30 min cycling bouts at a fixed rate of metabolic heat production (400 W) in the heat (35°C, 20% relative humidity). The exercise bouts were followed by 20 and 40 min of recovery, respectively. Forearm sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC, laser Doppler perfusion units/mean arterial pressure) were evaluated at four skin sites that were continuously perfused via intradermal microdialysis with: (1) lactated Ringer solution (Control), (2) 10 mm ketorolac (non-selective COX inhibitor), (3) 10 mm N(G) -nitro-l-arginine methyl ester (l-NAME; non-selective NOS inhibitor) or (4) a combination of 10 mm ketorolac + 10 mm l-NAME. Sweating was not different between the four sites during either exercise bout (main effect P = 0.92) (average of last 5 min of second exercise, Control, 0.80 ± 0.06; ketorolac, 0.77 ± 0.09; l-NAME, 0.74 ± 0.07; ketorolac + l-NAME, 0.77 ± 0.09 mg min(-1) cm(-2) ). During both exercise bouts, relative to CVC evaluated at the Control site (average of last 5 min of second exercise, 69 ± 6%max), CVC was similar at the ketorolac site (P = 0.62; 66 ± 4%max) whereas it was attenuated to a similar extent at both the l-NAME (49 ± 8%max) and ketorolac + l-NAME (54 ± 8%max) sites (both P < 0.05). Thus, we demonstrate that NOS and COX are not functionally involved in forearm sweating whereas only NOS contributes to forearm cutaneous vasodilatation in older adults during intermittent exercise in the heat.

At what level of heat load are age-related impairments in the ability to dissipate heat evident in females?

Studies have reported that older females have impaired heat loss responses during work in the heat compared to young females. However, it remains unclear at what level of heat stress these differences occur. Therefore, we examined whole-body heat loss [evaporative (HE) and dry heat loss, via direct calorimetry] and changes in body heat storage (∆Hb, via direct and indirect calorimetry) in 10 young (23±4 years) and 10 older (58±5 years) females matched for body surface area and aerobic fitness (VO2peak) during three 30-min exercise bouts performed at incremental rates of metabolic heat production of 250 (Ex1), 325 (Ex2) and 400 (Ex3) W in the heat (40°C, 15% relative humidity). Exercise bouts were separated by 15 min of recovery. Since dry heat gain was similar between young and older females during exercise (p=0.52) and recovery (p=0.42), differences in whole-body heat loss were solely due to HE. Our results show that older females had a significantly lower HE at the end of Ex2 (young: 383±34 W; older: 343±39 W, p=0.04) and Ex3 (young: 437±36 W; older: 389±29 W, p=0.008), however no difference was measured at the end of Ex1 (p=0.24). Also, the magnitude of difference in the maximal level of HE achieved between the young and older females became greater with increasing heat loads (Ex1=10.2%, Ex2=11.6% and Ex3=12.4%). Furthermore, a significantly greater ∆Hb was measured for all heat loads for the older females (Ex1: 178±44 kJ; Ex2: 151±38 kJ; Ex3: 216±25 kJ, p=0.002) relative to the younger females (Ex1: 127±35 kJ; Ex2: 96±45 kJ; Ex3: 146±46 kJ). In contrast, no differences in HE or ∆Hb were observed during recovery (p>0.05). We show that older habitually active females have an impaired capacity to dissipate heat compared to young females during exercise-induced heat loads of ≥325 W when performed in the heat.

Aging impairs heat loss, but when does it matter?

Aging is associated with an attenuated physiological ability to dissipate heat. However, it remains unclear if age-related impairments in heat dissipation only occur above a certain level of heat stress and whether this response is altered by aerobic fitness. Therefore, we examined changes in whole body evaporative heat loss (HE) as determined using whole body direct calorimetry in young (n = 10; 21 ± 1 yr), untrained middle-aged (n = 10; 48 ± 5 yr), and older (n = 10; 65 ± 3 yr) males matched for body surface area. We also studied a group of trained middle-aged males (n = 10; 49 ± 5 yr) matched for body surface area with all groups and for aerobic fitness with the young group. Participants performed intermittent aerobic exercise (30-min exercise bouts separated by 15-min rest) in the heat (40°C and 15% relative humidity) at progressively greater fixed rates of heat production equal to 300 (Ex1), 400 (Ex2), and 500 (Ex3) W. Results showed that HE was significantly lower in middle-aged untrained (Ex2: 426 ± 34; and Ex3: 497 ± 17 W) and older (Ex2: 424 ± 38; and Ex3: 485 ± 44 W) compared with young (Ex2: 472 ± 42; and Ex3: 558 ± 51 W) and middle-aged trained (474 ± 21; Ex3: 552 ± 23 W) males at the end of Ex2 and Ex3 (P < 0.05). No differences among groups were observed during recovery. We conclude that impairments in HE in older and middle-aged untrained males occur at exercise-induced heat loads of ≥400 W when performed in a hot environment. These impairments in untrained middle-aged males can be minimized through regular aerobic exercise training.

Age-related differences in postsynaptic increases in sweating and skin blood flow postexercise.

The influence of peripheral factors on the control of heat loss responses (i.e., sweating and skin blood flow) in the postexercise period remains unknown in young and older adults. Therefore, in eight young (22 ± 3 years) and eight older (65 ± 3 years) males, we examined dose-dependent responses to the administration of acetylcholine (ACh) and methacholine (MCh) for sweating (ventilated capsule), as well as to ACh and sodium nitroprusside (SNP) for cutaneous vascular conductance (CVC, laser-Doppler flowmetry, % of max). In order to assess if peripheral factors are involved in the modulation of thermoeffector activity postexercise, pharmacological agonists were perfused via intradermal microdialysis on two separate days: (1) at rest ( DOSE: ) and (2) following a 30-min bout of exercise ( EX+: DOSE: ). No differences in sweat rate between the DOSE and Ex+DOSE conditions at either ACh or MCh were observed for the young (ACh: P = 0.992 and MCh: P = 0.710) or older (ACh: P = 0.775 and MCh: P = 0.738) adults. Similarly, CVC was not different between the DOSE and Ex+DOSE conditions for the young (ACh: P = 0.123 and SNP: P = 0.893) or older (ACh: P = 0.113 and SNP: P = 0.068) adults. Older adults had a lower sweating response for both the DOSE (ACh: P = 0.049 and MCh: P = 0.006) and Ex+DOSE (ACh: P = 0.050 and MCh: P = 0.029) conditions compared to their younger counterparts. These findings suggest that peripheral factors do not modulate postexercise sweating and skin blood flow in both young and older adults. Additionally, sweat gland function is impaired in older adults, albeit the impairments were not exacerbated during postexercise recovery.

Cyclooxygenase inhibition does not alter methacholine-induced sweating.

Cholinergic agents (e.g., methacholine) induce cutaneous vasodilation and sweating. Reports indicate that either nitric oxide (NO), cyclooxygenase (COX), or both can contribute to cholinergic cutaneous vasodilation. Also, NO is reportedly involved in cholinergic sweating; however, whether COX contributes to cholinergic sweating is unclear. Forearm sweat rate (ventilated capsule) and cutaneous vascular conductance (CVC, laser-Doppler perfusion units/mean arterial pressure) were evaluated in 10 healthy young (24 ± 4 yr) adults (7 men, 3 women) at four skin sites that were continuously perfused via intradermal microdialysis with 1) lactated Ringer (control), 2) 10 mM ketorolac (a nonselective COX inhibitor), 3) 10 mM N(G)-nitro-l-arginine methyl ester (l-NAME, a nonselective NO synthase inhibitor), or 4) a combination of 10 mM ketorolac + 10 mM l-NAME. At the four skin sites, methacholine was simultaneously infused in a dose-dependent manner (1, 10, 100, 1,000, 2,000 mM). Relative to the control site, forearm CVC was not influenced by ketorolac throughout the protocol (all P > 0.05), whereas l-NAME and ketorolac + l-NAME reduced forearm CVC at and above 10 mM methacholine (all P < 0.05). Conversely, there was no main effect of treatment site (P = 0.488) and no interaction of methacholine dose and treatment site (P = 0.711) on forearm sweating. Thus forearm sweating (in mg·min(-1)·cm(-2)) from baseline up to the maximal dose of methacholine was not different between the four sites (at 2,000 mM, control 0.50 ± 0.23, ketorolac 0.44 ± 0.23, l-NAME 0.51 ± 0.22, and ketorolac + l-NAME 0.51 ± 0.23). We show that both NO synthase and COX inhibition do not influence cholinergic sweating induced by 1-2,000 mM methacholine.

Diminished nitric oxide-dependent sweating in older males during intermittent exercise in the heat.

Nitric oxide (NO) is a signalling molecule that contributes to the control of many physiological pathways, including the heat-loss response of skin vasodilatation. Recently, NO has been implicated in the control of sweating during exercise in young adults. We tested the hypothesis that ageing reduces NO-dependent sweating during exercise in the heat. Ten young (23 ± 3 years old) and 10 older men (64 ± 5 years old), matched for body surface area, performed three successive 15 min bouts of exercise (Ex1, Ex2 and Ex3) at the same rate of metabolic heat production (300 W m(-2)) in the heat (35°C, 20% relative humidity). Exercise periods were interspersed with 15 min recovery periods. Local sweat rate (ventilated capsule) was measured on two forearm skin sites, which were continuously perfused via intradermal microdialysis with 0.9% saline as control (CON) or 10 mm N(G)-nitro-l-arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor. Local sweat rate at the end of Ex1 was lower in the CON conditions in the older versus young men (0.69 ± 0.19 versus 0.90 ± 0.17 mg min(-1) cm(-2), P = 0.018). In the young men, local sweat rate was reduced in the L-NAME-treated conditions compared with the CON conditions at the end of Ex1 (0.67 ± 0.14 versus 0.90 ± 0.17 mg min(-1) cm(-2), P = 0.004), Ex2 (0.78 ± 0.20 versus 1.03 ± 0.20 mg min(-1) cm(-2), P = 0.013) and Ex3 (0.78 ± 0.20 versus 1.03 ± 0.21 mg min(-1) cm(-2), P = 0.014). In the older men, there was no main effect of treatment conditions on local sweat rate (P = 0.537) such that local sweat rates in the L-NAME-treated and CON conditions were similar (Ex1, 0.65 ± 0.20 versus 0.69 ± 0.19 mg min(-1) cm(-2); Ex2, 0.80 ± 0.27 versus 0.91 ± 0.29 mg min(-1) cm(-2); and Ex3, 0.84 ± 0.31 versus 0.94 ± 0.38 mg min(-1) cm(-2)). We conclude that ageing attenuates the influence of NO in the control of local forearm sweating observed in young adults during short 15 min bouts of exercise in the heat. This mechanism may, in part, explain the age-related impairments in sweating.

Do older adults experience greater thermal strain during heat waves?

Heat waves are the cause of many preventable deaths around the world, especially among older adults and in countries with more temperate climates. In the present study, we examined the effects of age on whole-body heat loss and heat storage during passive exposure to environmental conditions representative of the upper temperature extremes experienced in Canada. Direct and indirect calorimetry measured whole-body evaporative heat loss and dry heat exchange, as well as the change in body heat content. Twelve younger (21 ± 3 years) and 12 older (65 ± 5 years) adults with similar body weight (younger: 72.0 ± 4.4 kg; older: 80.1 ± 4.2 kg) and body surface area (younger: 1.8 ± 0.1 m(2); older: 2.0 ± 0.1 m(2)) rested for 2 h in a hot-dry [36.5 °C, 20% relative humidity (RH)] or hot-humid (36.5 °C, 60% RH) environment. In both conditions, evaporative heat loss was not significantly different between groups (dry: p = 0.758; humid: p = 0.814). However, the rate of dry heat gain was significantly greater (by approx. 10 W) for older adults relative to younger adults during the hot-dry (p = 0.032) and hot-humid exposure (p = 0.019). Consequently, the cumulative change in body heat content after 2 h of rest was significantly greater in older adults in the hot-dry (older: 212 ± 25 kJ; younger: 131 ± 27 kJ, p = 0.018) as well as the hot-humid condition (older: 426 ± 37 kJ; younger: 317 ± 45 kJ, p = 0.037). These findings demonstrate that older individuals store more heat during short exposures to dry and humid heat, suggesting that they may experience increased levels of thermal strain in such conditions than people of younger age.

Older adults with type 2 diabetes store more heat during exercise.

INTRODUCTION: It is unknown if diabetes-related reductions in local skin blood flow (SkBF) and sweating (LSR) measured during passive heat stress translate into greater heat storage during exercise in the heat in individuals with type 2 diabetes (T2D) compared with nondiabetic control (CON) subjects. PURPOSE: This study aimed to examine the effects of T2D on whole-body heat exchange during exercise in the heat. METHODS: Ten adults (6 males and 4 females) with T2D and 10 adults (6 males and 4 females) without diabetes matched for age, sex, body surface area, and body surface area and aerobic fitness cycled continuously for 60 min at a fixed rate of metabolic heat production (∼370 W) in a whole-body direct calorimeter (30°C and 20% relative humidity). Upper back LSR, forearm SkBF, rectal temperature, and heart rate were measured continuously. Whole-body heat loss and changes in body heat content (ΔHb) were determined using simultaneous direct whole-body and indirect calorimetry. RESULTS: Whole-body heat loss was significantly attenuated from 15 min throughout the remaining exercise with the differences becoming more pronounced over time for T2D relative to CON (P = 0.004). This resulted in a significantly greater ΔHb in T2D (367 ± 35; CON, 238 ± 25 kJ, P = 0.002). No differences were measured during recovery (T2D, -79 ± 23; CON, -132 ± 23 kJ, P = 0.083). By the end of the 60-min recovery, the T2D group lost only 21% (79 kJ) of the total heat gained during exercise, whereas their nondiabetic counterparts lost in excess of 55% (131 kJ). No difference were observed in LSR, SkBF, rectal temperature or heart rate during exercise. Similarly, no differences were measured during recovery with the exception that heart rate was elevated in the T2D group relative to CON (p=0.004). CONCLUSION: Older adults with T2D have a reduced capacity to dissipate heat during exercise, resulting in a greater heat storage and therefore level of thermal strain.

Whole-body heat loss during exercise in the heat is not impaired in type 1 diabetes.

PURPOSE: The objective of this study is to determine whether individuals with type 1 diabetes exhibit impairments in local and whole-body heat loss responses that could affect core temperature regulation during exercise in the heat compared with matched, nondiabetic individuals. METHODS: Twelve otherwise healthy individuals with type 1 diabetes (HbA1c = 7.7% ± 0.3%) and 12 controls matched for age, sex, body surface area, and physical fitness cycled continuously for 60 min at a set rate of metabolic heat production (approximately 400 W) in a whole-body direct calorimeter (35°C and 20% relative humidity). Local sweat rate (ventilated capsule) was measured on the back and skin blood flow (laser Doppler velocimetry) on the forearm. Core (rectal and esophageal) and mean skin temperatures and heart rate were measured continuously. Whole-body heat exchange and change in body heat content were measured using simultaneous direct whole-body and indirect calorimetry. RESULTS: The change (mean ± SE) in body heat content was similar between groups during exercise (diabetes, 409 ± 27 kJ; control, 386 ± 33 kJ; P = 0.584) and recovery (diabetes, -115 ± 16 kJ; control, -93 ± 24 kJ; P = 0.457). Local heat loss responses of sweating (P = 0.783) and skin blood flow (P = 0.078) as well as rectal temperature (diabetes, 37.87°C ± 0.10°C; control, 37.85°C; ± 0.13°C; P = 0.977) and heart rate (diabetes, 130 ± 9 beats·min, vs control, 126 ± 8 beats·min, P = 0.326) were comparable at the end of the exercise period. CONCLUSION: During light-to-moderate-intensity exercise performed under conditions permitting full sweat evaporation, otherwise healthy type 1 diabetic individuals did not show impaired heat loss responses during heat exposure when compared with matched individuals without diabetes.

Do heat events pose a greater health risk for individuals with type 2 diabetes?

Chronic medical conditions such as type 2 diabetes may alter the body's normal response to heat. Evidence suggests that the local heat loss response of skin blood flow (SkBF) is affected by diabetes-related impairments in both endothelium-dependent and non-endothelium-dependent mechanisms, resulting in lower elevations in SkBF in response to a heat or pharmacological stimulus. Thermoregulatory sweating may also be diminished by type 2 diabetes, impairing the body's ability to transfer heat from its core to the environment. Diabetes-associated co-morbidities and the medications (particularly those affecting fluid balance) required to treat these conditions may exacerbate the risk of heat-related illness by decreasing SkBF and sweating further. Unfortunately, the majority of studies measure local heat loss responses in the hands and feet and lack measures of core temperature. Therefore, the impact of these impairments on whole-body heat loss remains unknown. This review addresses heat-related vulnerability in individuals with type 2 diabetes by examining the literature related to heat loss responses in this population. Type 2 diabetes, its associated co-morbidities, and the medications required in their treatment may cause dehydration, lower SkBF, and reduced sweating, which could consequently impair thermoregulation. This effect is most evident in individuals with poor blood glucose control. Although type 2 diabetes can be associated with impairments in SkBF and sweating, more physically active individuals requiring fewer medications and having good blood glucose control may be able to tolerate heat as well as those of similar age and body composition.

Is whole-body thermoregulatory function impaired in type 1 diabetes mellitus?

UNLABELLED: During periods of extreme heat individuals with diabetes have greater rates of heat-related morbidity and mortality compared to their non-diabetic counterparts. The reason for this discrepancy is currently unknown. Furthermore, there is a lack of information about whether or not individuals with type 1 diabetes are at a thermoregulatory disadvantage during strenuous physical activity especially when performed in the heat. PURPOSE: This review discusses the current literature pertaining to thermoregulatory responses in individuals with type 1 diabetes. METHODS: We included 14 reviews and 95 original research articles identified by searches of PubMed and Google Scholar and deemed relevant to our subject by three independent readers. RESULTS: Individuals with poorly controlled type 1 diabetes may have impaired heat sensation, and a reduced capacity to dissipate heat due to lower skin blood flow and sweating responses and a greater tendency towards dehydration compared to individuals without diabetes. Impairments may be attenuated or absent in those with good blood glucose control. We found no published studies examining thermoregulatory responses to physical activity in the heat in individuals with type 1 diabetes. CONCLUSIONS: Type 1 diabetes may cause impairments in heat loss resulting in a greater level of thermal strain. Advancement in our understanding about the effects of type 1 diabetes on the heat stress response, especially during different challenges to human heat balance associated with changes in both environmental heat load and metabolic heat production (physical activity), will help us to determine where the risk of heat-illness/injury actually exists.

Body heat storage during intermittent work in hot-dry and warm-wet environments.

We examined heat balance using an American Conference of Governmental Industrial Hygienists threshold limit value allocated exercise protocol in hot-dry (HD; 46 °C, 10% relative humidity (RH)) and warm-wet (WW; 33 °C, 60% RH) environments of equivalent WBGT (29 °C) for different clothing ensembles. Whole-body heat exchange and changes in body heat content (ΔH(b)) were measured using simultaneous direct whole-body and indirect calorimetry. Eight males performed six 15-min cycling periods at a constant rate of metabolic heat production (360 W) interspersed by 5-min rest periods for six experimental trials: HD and WW environments for a seminude control (CON), modified work uniform (MWU, moisture permeable top and work pants), and standard work uniform (SWU, work coveralls and cotton undergarments). Whole-body evaporative and dry heat exchange, rectal temperature (T(re)), and heart rate were measured continuously. The cumulative ΔH(b) during the 2 h intermittent exercise protocol was similar between HD and WW environments for each of the clothing ensembles (CON, 387 ± 55 vs. 435 ± 49 kJ; MWU, 485 ± 58 vs. 531 ± 61 kJ; SWU, 585 ± 74 vs. 660 ± 54 kJ, respectively). Similarly, no differences in T(re) (CON, 37.67 ± 0.07 vs. 37.48 ± 0.08 °C; MWU, 37.73 ± 0.08 vs. 37.53 ± 0.09 °C; SWU, 38.01 ± 0.09 vs. 37.94 ± 0.05 °C) or heat rate (CON, 93 ± 3 vs. 84 ± 3 beats·min⁻¹; MWU, 102 ± 5 vs. 95 ± 9 beats·min⁻¹; SWU, 119 ± 8 vs. 110 ± 9 beats·min⁻¹) were observed at the end of the 2 h intermittent exercise protocol in HD vs. WW environments, respectively. We showed similar levels of thermal and cardiovascular strain for intermittent work performed in high heat stress conditions of varying environmental conditions but similar WBGT.

Cortisol and interleukin-6 responses during intermittent exercise in two different hot environments with equivalent WBGT.

Blood marker concentrations such as cortisol (COR) and interleukin (IL)-6 are commonly used to evaluate the physiological strain associated with work in the heat. It is unclear, however, if hot environments of an equivalent thermal stress, as defined by a similar wet bulb globe temperature (WBGT), result in similar response patterns. This study examined markers of neuroendocrine (COR) and immune (IL-6) responses, as well as the cardiovascular and thermal responses, relative to changes in body heat content measured by whole-body direct calorimetry during work in two different hot environments with equivalent WBGT. Eight males performed a 2-hr heavy intermittent exercise protocol (six 15-min bouts of cycling at a constant rate of metabolic heat production (360W) interspersed by 5-min rest periods) in Hot/Dry (46°C, 10% relative humidity [RH]) and Warm/Humid (33°C, 60% RH) conditions (WBGT ∼ 29°C). Whole-body evaporative and dry heat exchange, change in body heat content (ΔH(b)), rectal temperature (T(re)), and heart rate were measured continuously. Venous blood was obtained at rest (PRE) and the end of each exercise bout for the measurement of changes in plasma volume (PV), plasma protein (an estimate of plasma water changes), COR, and IL-6. Ratings of perceived exertion and thermal sensation were measured during the last minute of each exercise bout. No differences existed for ΔH(b), heart rate, T(re),%ΔPV, plasma protein concentration, perceptual strain (thermal sensation, perceived exertion), and COR between the Hot/Dry and Warm/Humid conditions. IL-6 exhibited an interaction effect (p = 0.041), such that greater increases were observed in the Hot/Dry (Δ = 1.61 pg·mL(-1)) compared with the Warm/Humid (Δ = 0.64 pg·mL(-1)) environment. These findings indicate that work performed in two different hot environments with equivalent WBGT resulted in similar levels of thermal, cardiovascular, and perceptual strain, which support the use of the WBGT stress index. However, the greater IL-6 response in the Hot/Dry requires further research to elucidate the effects of different hot environments and work intensities.

The influence of activewear worn under standard work coveralls on whole-body heat loss.

This study evaluated the influence of activewear undergarments worn under the standard mining coveralls on whole-body heat exchange and change in body heat content during work in the heat. Each participant performed 60 min of cycling at a constant rate of heat production of 400 W followed by 60 min of recovery in a whole-body calorimeter regulated at 40°C and 15% relative humidity donning one of the four clothing ensembles: (1) cotton underwear and shorts only (Control, CON); (2) Activewear only (ACT); (3) Coveralls+Cotton undergarments (COV+COT); or (4) Coveralls+Activewear undergarments (COV+ACT). In the latter two conditions a hard hat with earmuffs, gloves, and socks with closed toe shoes were worn. We observed that both COV+COT and COV+ACT resulted in a similar mean (±SE) change in body heat content, which was significantly greater compared with the CON and ACT during exercise, suggesting that the rate of thermal strain was elevated to a similar degree in both coverall conditions (CON: 245±32 kJ; ACT: 260±29 kJ; COV+COT: 428±36 kJ; COV+ACT: 466±15 kJ; p<0.001). During recovery, the negative change in body heat content was greater for both COV+COT and COV+ACT compared with the CON and ACT but similar between COV+COT and COV+ACT due to the greater amount of heat stored during exercise (CON: -83±16 kJ; ACT: -104±33 kJ; COV+COT: -198±30 kJ; COV+ACT: -145±12 kJ; p=0.048). Core temperatures and heart rate were also significantly elevated for the COV+COT and COV+ACT compared with the CON and ACT conditions during and following exercise (p<0.05). These results suggest that while activewear undergarments are not detrimental, they provide no thermoregulatory benefit when replacing the cotton undergarment worn under the standard coverall during work in the heat.