KCa channels are major contributors to ATP-induced cutaneous vasodilation in healthy older adults.

OBJECTIVE: To examine the contributions of calcium-activated K+ (KCa) channels and nitric oxide synthase (NOS) to adenosine triphosphate (ATP)-induced cutaneous vasodilation in healthy older adults. METHODS: In eleven older adults (69 ± 2 years, 5 females), cutaneous vascular conductance, normalized to maximum vasodilation (%CVCmax) was assessed at four dorsal forearm skin sites that were continuously perfused with either 1) lactated Ringer solution (Control), 2) 50 mM tetraethylammonium (TEA, KCa channel blocker), 3) 10 mM Nω-nitro-L-arginine (L-NNA, NOS inhibitor), or 4) combined 50 mM TEA +10 mM L-NNA, via microdialysis. Local skin temperature was fixed at 33 °C at all sites with local heaters throughout the protocol while the cutaneous vasodilator response was assessed during coadministration of ATP (0.03, 0.3, 3, 30, 300 mM; 20 min per dose), followed by 50 mM sodium nitroprusside and local skin heating to 43 °C to achieve maximum vasodilation (20-30 min). RESULTS: Blockade of KCa channels blunted %CVCmax relative to Control from 0.3 to 300 mM ATP (All P < 0.05). A similar response was observed for the combined KCa channel blockade and NOS inhibition site from 3 to 300 mM ATP (All P < 0.05). Conversely, NOS inhibition alone did not influence %CVCmax across all ATP doses (All P > 0.05). CONCLUSION: In healthy older adults, KCa channels play an important role in modulating ATP-induced cutaneous vasodilation, while the NOS contribution to this response is negligible.

Heat shock protein 90 modulates cutaneous vasodilation during an exercise-heat stress, but not during passive whole-body heating in young women.

Heat shock protein 90 (HSP90) modulates exercise-induced cutaneous vasodilation in young men via nitric oxide synthase (NOS), but only when core temperature is elevated ~1.0°C. While less is known about modulation of this heat loss response in women during exercise, sex differences may exist. Further, the mechanisms regulating cutaneous vasodilation can differ between exercise- and passive-heat stress. Therefore, in 11 young women (23 ± 3 years), we evaluated whether HSP90 contributes to NOS-dependent cutaneous vasodilation during exercise (Protocol 1) and passive heating (Protocol 2) and directly compared responses between end-exercise and a matched core temperature elevation during passive heating. Cutaneous vascular conductance (CVC%max ) was measured at four forearm skin sites continuously treated with (a) lactated Ringers solution (control), (b) 178 µM Geldanamycin (HSP90 inhibitor), (c) 10 mM L-NAME (NOS inhibitor), or (d) combined 178 µM Geldanamycin and 10 mM L-NAME. Participants completed both protocols during the early follicular (low hormone) phase of the menstrual cycle (0-7 days). Protocol 1: participants rested in the heat (35°C) for 70 min and then performed 50 min of moderate-intensity cycling (~55% VO2peak ) followed by 30 min of recovery. Protocol 2: participants were passively heated to increase rectal temperature by 1.0°C, comparable to end-exercise. HSP90 inhibition attenuated CVC%max relative to control at end-exercise (p < .05), but not during passive heating. While NOS inhibition and combined HSP90 + NOS inhibition attenuated CVC%max relative to control for both protocols (all p < .05), they did not differ from each other. We show that HSP90 modulates cutaneous vasodilation NOS-dependently during exercise in young women, with no effect during passive heating, despite a similar NOS contribution.

Regional influence of nitric oxide on cutaneous vasodilatation and sweating during exercise-heat stress in young men.

NEW FINDINGS: What is the central question of this study? Do regional differences exist in nitric oxide synthase (NOS)-dependent cutaneous vasodilatation and sweating during exercise-heat stress in young men. What is the main finding and its importance? Exercise-induced increases in cutaneous vasodilatation and sweating were greater on the chest and upper back compared to the forearm, although the NOS contribution to cutaneous vasodilatation was similar across all regions. Conversely, there was a greater NOS-dependent rate of change in sweating on the chest compared to the forearm, with a similar trend on the back. ABSTRACT: While it is established that nitric oxide synthase (NOS) is an important modulator of forearm cutaneous vasodilatation and sweating during an exercise-heat stress in young men, it remains unclear if regional differences exist in this response. In 15 habitually active young men (24 ± 4 (SD) years), cutaneous vascular conductance (CVC) and local sweat rate (LSR) were assessed at three body regions. On each of the dorsal forearm, chest and upper-back (trapezius), sites were continuously perfused with either (1) lactated Ringer solution (control) or (2) 10 Mm Nω -nitro-l-arginine (l-NNA, NOS inhibitor), via microdialysis. Participants rested in the heat (35°C) for ∼75 min, followed by 60 min of semi-recumbent cycling performed at a fixed rate of heat production of 200 W m-2 (equivalent to ∼42% V̇O2peak ). During exercise, the chest and upper-back regions showed higher CVC and LSR responses relative to the forearm (all P < 0.05). Within each region, l-NNA attenuated CVC and LSR relative to control (all P < 0.05). However, the NOS contribution was not different across regions for the rate of change and plateau for CVC or for the LSR plateau (all P > 0.05). Conversely, there was a greater NOS contribution to the rate of change for LSR at the chest relative to the forearm (P < 0.05) with a similar trend for the back. In habitually active young men, NOS-dependent cutaneous vasodilatation was similar across regions while the NOS contribution to LSR was greater on the chest relative to the forearm. These findings advance our understanding of the mechanisms influencing regional variations in cutaneous vasodilatation and sweating during an exercise-heat stress.

Intradermal Administration of Atrial Natriuretic Peptide Attenuates Cutaneous Vasodilation but Not Sweating in Young Men during Exercise in the Heat.

INTRODUCTION: Prolonged exercise in the heat stimulates plasma release of atrial natriuretic peptide (ANP) in association with dehydration-induced reductions in blood volume. Elevated plasma ANP levels under these conditions may indirectly attenuate cutaneous blood flow and sweating responses due to the effects of this hormone on central blood volume and plasma osmolality and the resulting stimulation of nonthermal reflexes. However, it remains unclear whether cutaneous blood flow and sweating are directly modulated by ANP at the level of the cutaneous end organs (cutaneous microvessels and eccrine sweat glands) during prolonged exercise in the heat. OBJECTIVE: Therefore, we evaluated the effects of local ANP administration on forearm cutaneous vascular conductance (CVC) and local sweat rate (LSR) during rest and exercise in the heat. METHODS: In 9 habitually active young men (26 ± 6 years) CVC and LSR were evaluated at 3 intradermal microdialysis sites continuously perfused with lactated Ringer solution (control) or ANP (0.1 or 1.0 µM). Participants rested in a non-heat-stress condition (25°C) for approximately 60 min followed by 70 min in the heat (35°C). They then performed 50 min of moderate-intensity cycling (approx. 55% VO2 peak), with a 30-min recovery. Thereafter, 50 mM sodium nitroprusside was administered at all sites to elicit maximum CVC, which was subsequently used to normalize all values (CVC%max). RESULTS: No effects of ANP on CVC%max were observed in the non-heat-stress resting condition compared to the untreated control site (both p > 0.05). Conversely during rest in the heat there was an 11% (5-17%) reduction in CVC%max at the 1.0 µM ANP site relative to the untreated control site (p < 0.05). At the end of exercise CVC%max was attenuated by 12% (1-23%) at the 0.1 µM ANP site and by 21% (7-35%) at the 1.0 µM ANP site relative to the untreated control site (all p < 0.05). Conversely, neither concentration of ANP influenced sweating at any time point (all p > 0.05). CONCLUSION: Intradermal ANP administration directly attenuated cutaneous blood flow, but not sweating, in habitually active young men during rest and exercise in the heat.

Whole-body heat exchange in black-African and Caucasian men during exercise eliciting matched heat-loss requirements in dry heat.

NEW FINDINGS: What is the central question of this study? Black-African descendants are thought, by some, to possess genotypic adaptations conducive to survival in hot climates. We therefore assessed whether Canadian residents of black-African descent display enhanced whole-body total heat loss (evaporative plus dry heat exchange) in comparison to Caucasian Canadians during exercise eliciting matched heat-loss requirements in dry heat. What is the main finding and its importance? Neither whole-body total heat loss nor body heat storage differed significantly between groups, irrespective of the exercise intensity. Our findings indicate that genotypic adaptations associated with ethnicity do not appreciably modify whole-body heat exchange during exercise-heat stress. ABSTRACT: Ethnicity has long been thought to modulate thermoregulatory function; however, an evaluation of whole-body heat exchange in men of black-African descent and Caucasian men (white-European descendants), born and raised in the same climate, during exercise eliciting matched heat-loss requirements remained unavailable. We therefore used direct calorimetry to assess whole-body total heat loss (evaporative plus dry heat exchange) in young (18-30 years of age), second-generation (or higher) black-African (n = 11) and Caucasian (n = 11) men. Participants performed three 30 min bouts of semi-recumbent cycling at fixed metabolic heat productions (and therefore matched heat-loss requirements between groups) of 200 (light), 250 (moderate) and 300 W m-2 (vigorous), each followed by 15 min recovery, in dry heat (40°C, ∼13% relative humidity). Across all exercise bouts, dry (P = 0.435) and evaporative (P = 0.600) heat exchange did not differ significantly between groups. As such, total heat loss during light, moderate and vigorous exercise was similar between groups (P = 0.777), averaging [mean (SD)] 177 (10), 217 (13) and 244 (20) W m-2 in black-African men and 172 (13), 212 (17) and 244 (17) W m-2 in Caucasian men. Accordingly, body heat storage across all exercise bouts (summation of metabolic heat production and total heat loss) was also similar between the black-African [568 (142) kJ] and Caucasian groups [623 (124) kJ; P = 0.356]. We demonstrated that, when assessed in young, second-generation (or higher) black-African and Caucasian men during exercise eliciting matched heat-loss requirements in dry heat, ethnicity did not significantly modulate whole-body dry and evaporative heat exchange or the resulting changes in total heat loss and body heat storage.

Contribution of nitric oxide synthase to cutaneous vasodilatation and sweating in men of black-African and Caucasian descent during exercise in the heat.

NEW FINDINGS: What is the central question of this study? Nitric oxide modulates cutaneous vasodilatation and sweating during exercise-induced heat stress in young men. However, it remains uncertain whether these effects are reduced in black-African descendants, who commonly demonstrate reduced nitric oxide bioavailability. Therefore, we assessed whether black-African descendants display reduced nitric oxide-dependent cutaneous vasodilatation and sweating compared with Caucasians in these conditions. What is the main finding and its importance? Nitric oxide-dependent cutaneous vasodilatation and sweating were similar between groups, indicating that reduced nitric oxide bioavailability in black-African descendants does not attenuate these heat-loss responses during an exercise-induced heat stress. ABSTRACT: Men of black-African descent are at an increased risk of heat-related illness relative to their Caucasian counterparts. This might be attributable, in part, to reduced cutaneous nitric oxide (NO) bioavailability in this population, which might alter local cutaneous vasodilatation and sweating. To evaluate this, we compared these heat-loss responses in young men (18-30 years of age) of black-African (n = 10) and Caucasian (n = 10) descent during rest, exercise and recovery in the heat. Participants were matched for physical characteristics and fitness, and they were all born and raised in the same temperate environment (i.e. Canada; second generation and higher). Both groups rested for 10 min and then performed 50 min of moderate-intensity exercise at 200 W m-2 , followed by 30 min of recovery in hot, dry heat (35°C, 20% relative humidity). Local cutaneous vascular conductance (CVC%max ) and sweat rate (SR) were measured at two forearm skin sites treated with either lactated Ringer solution (control) or 10 mm NG -nitro-l-arginine methyl ester (l-NAME, a nitric oxide (NO) synthase inhibitor). l-NAME significantly reduced CVC%max throughout rest, exercise and recovery in both groups (both P < 0.001). However, there were no significant main effects for the contribution of NO to CVC%max between groups (all P > 0.500). l-NAME significantly reduced local SR in both groups (both P < 0.050). The contribution of NO to SR was similar between groups such that l-NAME reduced SR relative to control at 40 and 50 min into exercise (both P < 0.05). We demonstrate that ethnicity per se does not influence NO-dependent cutaneous vasodilatation and sweating in healthy young men of black-African and Caucasian descent during exercise in dry heat.

Separate and combined effects of KCa and KATP channel blockade with NOS inhibition on cutaneous vasodilation and sweating in older men during heat stress.

Our objective in this study was to examine the separate and combined effects of potassium (K+) channels and nitric oxide synthase (NOS) on cutaneous vasodilation and sweating in older men during rest and exercise in the heat. In 13 habitually active men (61 ± 4 yr), cutaneous vascular conductance and local sweat rate were assessed at six dorsal forearm skin sites continuously perfused with either 1) lactated Ringer (control), 2) 10 mM NG-nitro-l-arginine methyl ester (l-NAME, NOS inhibitor), 3) 50 mM tetraethylammonium (TEA; Ca2+-activated K+ channel blocker), 4) 5 mM glybenclamide (GLY; ATP-sensitive K+ channel blocker), 5) 50 mM TEA + 10 mM l-NAME, and 6) 5 mM GLY + 10 mM l-NAME via microdialysis. Participants rested in non-heat stress (25°C) and heat stress (35°C) conditions for ∼60 min each, followed by 50 min of moderate-intensity cycling (∼55% V̇o2peak) and 30 min of recovery in the heat. During rest and exercise in the heat, l-NAME, TEA + l-NAME, and GLY + l-NAME attenuated CVC relative to control (all P ≤ 0.05), although l-NAME was not different from TEA + l-NAME or GLY + l-NAME (all P > 0.05). TEA attenuated CVC during rest, whereas GLY attenuated CVC during exercise (both P ≤ 0.05). Additionally, whereas neither l-NAME nor TEA altered sweating throughout the protocol (all P > 0.05), combined TEA + l-NAME attenuated sweating during exercise in the heat (P ≤ 0.05). We conclude that in habitually active older men blockade of KCa and KATP channels attenuates cutaneous vasodilation during rest and exercise in the heat, respectively, and these effects are NOS dependent. Furthermore, combined NOS inhibition and KCa channel blockade attenuates sweating during exercise in the heat.

Heat shock protein 90 does not contribute to cutaneous vasodilatation in older adults during heat stress.

OBJECTIVES: Heat shock protein 90 (HSP90) contributes to cutaneous vasodilatation during exercise in the heat through nitric oxide (NO) synthase (NOS)-dependent mechanisms in young adults. We hypothesized that similar responses would be observed in older middle-aged adults. METHODS: In nineteen habitually active older middle-aged (56 ± 5 years) men (n = 9) and women (n = 10), cutaneous vascular conductance (CVC) was measured at four forearm skin sites continuously treated with (a) lactated Ringers solution (Control), (b) 10 mmol/L L-NAME (NOS inhibitor), (c) 178 µmol/L geldanamycin (HSP90 inhibitor), or (d) 10 mmol/L L-NAME and 178 µmol/L geldanamycin combined. Participants rested in an upright semi-recumbent position in the heat (35°C) for 70 minutes, followed by a 50-minute bout of moderate-intensity cycling (~55% peak oxygen uptake) and a 30-minute recovery period in the heat. RESULTS: In both men and women, we observed no significant effects of HSP90 inhibition on CVC throughout rest, exercise, and recovery in the heat (all P > 0.27). Conversely, NOS inhibition and dual NOS and HSP90 inhibition attenuated CVC relative to Control throughout the protocol (all P ≤ 0.05). CONCLUSIONS: While NOS mediates cutaneous vasodilatation during rest, exercise, and recovery in the heat, HSP90 does not measurably influence this response in habitually active older middle-aged men or women under these conditions.