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.

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.

Atrial natriuretic peptide (ANP) is a hormone secreted by cardiac muscle cells in response to increases in right atrial pressure, which can occur due to changes in blood pressure and blood volume. This hormone is also secreted during acute exercise in both temperate and hot environments and may be released into the blood due to the effects of increased venous return on the heart caused by active muscle contraction under these conditions. However, ANP release is diminished during prolonged exercise, which may ultimately impair heat loss if its release is linked to alterations in cutaneous blood flow and sweating. The current evidence is mixed with respect to a direct role of ANP in modulating cutaneous vasodilation and sweating responses, with some studies demonstrating an effect of exogenous ANP infusion in augmenting these heat loss responses, while others have failed to show any influence of the hormone. Thus, the purpose of this study was to evaluate the effects of intradermal administration of varying doses of ANP on cutaneous vasodilation and sweating responses in healthy habitually active young men exercising in a hot environment. Ten healthy young males (27 ± 6 years) exercised for 50 min at ~55% VO2peak in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC, measured via laser Doppler flowmetry) and sweating (measured via ventilated capsules) were assessed at four dorsal forearm skin sites receiving either lactated Ringer's solution (Control) or one of three ANP doses (0.1 μM, 1.0 μM, 10 μM) via microdialysis. At the end of exercise, CVC was not different between Control (73 ± 14% CVCmax) and 0.1 μM (66 ± 20% CVCmax), 1.0 μM (69 ± 21% CVCmax), or 10 μM (71 ± 18% CVCmax) ANP sites (all P > 0.05). Similarly, sweat rates were not different between Control (1.37 ± 0.43 mg/min/cm2) and 0.1 μM (1.43 ± 0.55 mg/min/cm2), 1.0 μM (1.44 ± 0.41 mg/min/cm2), or 10 μM (1.36 ± 0.37 mg/min/cm2) ANP sites (all P > 0.05). In summary, these results demonstrate that in healthy habitually active young men, intradermal administration of ANP does not augment cutaneous vasodilation or sweating during exercise in the heat. Such findings may indicate that ANP does not have a direct effect on these heat loss responses. Alternatively, it may be the case that endogenous levels of ANP produced under these conditions are sufficient to elicit a maximal effect of the hormone on cutaneous blood flow and sweating in healthy young men, thus masking any direct effects of exogenous administration. Support or Funding Information Funding support: Canadian Institutes of Health Research (held by Dr. Kenny). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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.

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.