Hyperthermia modifies muscle metaboreceptor and baroreceptor modulation of heat loss in humans

The relative influence of muscle metabo- and baroreflex activity on heat loss responses during post-isometric handgrip (IHG) exercise ischemia remains unknown, particularly under heat stress. Therefore, we examined the separate and integrated influences of metabo- and baroreceptor-mediated reflex activity on sweat rate and cutaneous vascular conductance (CVC) under increasing levels of hyperthermia. Twelve men performed 1 min of IHG exercise at 60% of maximal voluntary contraction followed by 2 min of ischemia with simultaneous application of lower body positive pressure (LBPP, +40 mmHg), lower body negative pressure (LBNP, -20 mmHg), or no pressure (control) under no heat stress. On separate days, trials were repeated under heat stress conditions of 0.6°C (moderate heat stress) and 1.4°C (high heat stress) increase in esophageal temperature. For all conditions, mean arterial pressure was greater with LBPP and lower with LBNP than control during ischemia (all P ≤ 0.05). No differences in sweat rate were observed between pressure conditions, regardless of the level of hyperthermia (P > 0.05). Under moderate heat stress, no differences in CVC were observed between pressure conditions. However, under high heat stress, LBNP significantly reduced CVC by 21 ± 4% (P ≤ 0.05) and LBPP significantly elevated CVC by 14 ± 5% (P ≤ 0.05) relative to control. These results show that sweating during post-IHG exercise ischemia is activated by metaboreflex stimulation, and not by baroreflexes. In contrast, our results suggest that baroreflexes can influence the metaboreflex modulation of CVC, but only at greater levels of hyperthermia.     

Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise in humans.

The hypothesis that baroreceptor unloading during dynamic limits cutaneous vasodilation by withdrawal of active vasodilator activity was tested in seven human subjects. Increases in forearm skin blood flow (laser-Doppler velocimetry) at skin sites with (control) and without alpha-adrenergic vasoconstrictor activity (vasodilator only) and in arterial blood pressure (noninvasive) were measured and used to calculate cutaneous vascular conductance (CVC). Subjects performed two similar dynamic exercise (119 +/- 8 W) protocols with and without baroreceptor unloading induced by application of -40 mmHg lower body negative pressure (LBNP). The LBNP condition was reversed (i.e., either removed or applied) after 15 min while exercise continued for an additional 15 min. During exercise without LBNP, the increase in body core temperature (esophageal temperature) required to elicit active cutaneous vasodilation averaged 0.25 +/- 0.08 and 0.31 +/- 0.10 degrees C (SE) at control and vasodilator-only skin sites, respectively, and increased to 0.44 +/- 0.10 and 0.50 +/- 0.10 degrees C (P < 0.05 compared with without LBNP) during exercise with LBNP. During exercise baroreceptor unloading delayed the onset of cutaneous vasodilation and limited peak CVC at vasodilator-only skin sites. These data support the hypothesis that during exercise baroreceptor unloading modulates active cutaneous vasodilation.     

Skin surface cooling improves orthostatic tolerance following prolonged head-down bed rest

Prolonged exposure to microgravity, as well as its ground-based analog, head-down bed rest (HDBR), reduces orthostatic tolerance in humans. While skin surface cooling improves orthostatic tolerance, it remains unknown whether this could be an effective countermeasure to preserve orthostatic tolerance following HDBR. We therefore tested the hypothesis that skin surface cooling improves orthostatic tolerance after prolonged HDBR. Eight subjects (six men and two women) participated in the investigation. Orthostatic tolerance was determined using a progressive lower-body negative pressure (LBNP) tolerance test before HDBR during normothermic conditions and on day 16 or day 18 of 6° HDBR during normothermic and skin surface cooling conditions (randomized order post-HDBR). The thermal conditions were achieved by perfusing water (normothermia ～34°C and skin surface cooling ～12-15°C) through a tube-lined suit worn by each subject. Tolerance tests were performed after ～30 min of the respective thermal stimulus. A cumulative stress index (CSI; mmHg LBNP·min) was determined for each LBNP protocol by summing the product of the applied negative pressure and the duration of LBNP at each stage. HDBR reduced normothermic orthostatic tolerance as indexed by a reduction in the CSI from 1,037 ± 96 mmHg·min to 574 ± 63 mmHg·min (P < 0.05). After HDBR, skin surface cooling increased orthostatic tolerance (797 ± 77 mmHg·min) compared with normothermia (P < 0.05). While the reduction in orthostatic tolerance following prolonged HDBR was not completely reversed by acute skin surface cooling, the identified improvements may serve as an important and effective countermeasure for individuals exposed to microgravity, as well as immobilized and bed-stricken individuals.     

Antagonism of soluble guanylyl cyclase attenuates cutaneous vasodilation during whole body heat stress and local warming in humans

We hypothesized that nitric oxide activation of soluble guanylyl cyclase (sGC) participates in cutaneous vasodilation during whole body heat stress and local skin warming. We examined the effects of the sGC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on reflex skin blood flow responses to whole body heat stress and on nonreflex responses to increased local skin temperature. Blood flow was monitored by laser-Doppler flowmetry, and blood pressure by Finapres to calculate cutaneous vascular conductance (CVC). Intradermal microdialysis was used to treat one site with 1 mM ODQ in 2% DMSO and Ringer, a second site with 2% DMSO in Ringer, and a third site received Ringer. In protocol 1, after a period of normothermia, whole body heat stress was induced. In protocol 2, local heating units warmed local skin temperature from 34 to 41°C to cause local vasodilation. In protocol 1, in normothermia, CVC did not differ among sites [ODQ, 15 ± 3% maximum CVC (CVC(max)); DMSO, 14 ± 3% CVC(max); Ringer, 17 ± 6% CVC(max); P > 0.05]. During heat stress, ODQ attenuated CVC increases (ODQ, 54 ± 4% CVC(max); DMSO, 64 ± 4% CVC(max); Ringer, 63 ± 4% CVC(max); P < 0.05, ODQ vs. DMSO or Ringer). In protocol 2, at 34°C local temperature, CVC did not differ among sites (ODQ, 17 ± 2% CVC(max); DMSO, 18 ± 4% CVC(max); Ringer, 18 ± 3% CVC(max); P > 0.05). ODQ attenuated CVC increases at 41°C local temperature (ODQ, 54 ± 5% CVC(max); DMSO, 86 ± 4% CVC(max); Ringer, 90 ± 2% CVC(max); P < 0.05 ODQ vs. DMSO or Ringer). sGC participates in neurogenic active vasodilation during heat stress and in the local response to direct skin warming.     

Does local heating-induced nitric oxide production attenuate vasoconstrictor responsiveness to lower body negative pressure in human skin?

We tested the hypothesis that local heating-induced nitric oxide (NO) production attenuates cutaneous vasoconstrictor responsiveness. Eleven subjects (6 men, 5 women) had four microdialysis membranes placed in forearm skin. Two membranes were perfused with 10 mM of N(G)-nitro-L-arginine (L-NAME) and two with Ringer solution (control), and all sites were locally heated to 34 degrees C. Subjects then underwent 5 min of 60-mmHg lower body negative pressure (LBNP). Two sites (a control and an L-NAME site) were then heated to 39 degrees C, while the other two sites were heated to 42 degrees C. At the L-NAME sites, skin blood flow was elevated using 0.75-2 mg/ml of adenosine in the perfusate solution (Adn + L-NAME) to a similar level relative to control sites. Subjects then underwent another 5 min of 60-mmHg LBNP. At 34 degrees C, cutaneous vascular conductance (CVC) decreased (Delta) similarly at both control and L-NAME sites during LBNP (Delta7.9 +/- 3.0 and Delta3.4 +/- 0.8% maximum, respectively; P > 0.05). The reduction in CVC to LBNP was also similar between control and Adn + L-NAME sites at 39 degrees C (control Delta11.4 +/- 2.5 vs. Adn + L-NAME Delta7.9 +/- 2.0% maximum; P > 0.05) and 42 degrees C (control Delta1.9 +/- 2.7 vs. Adn + L-NAME Delta 4.2 +/- 2.7% maximum; P > 0.05). However, the decrease in CVC at 42 degrees C, regardless of site, was smaller than at 39 degrees C (P < 0.05). These results do not support the hypothesis that local heating-induced NO production attenuates cutaneous vasoconstrictor responsiveness during high levels of LBNP. However, elevated local temperature, per se, attenuates cutaneous vasoconstrictor responsiveness to LBNP, presumably through non-nitric oxide mechanisms.     

Exercise-rest cycles do not alter local and whole body heat loss responses

Previous studies have suggested that greater core temperatures during intermittent exercise (Ex) are due to attenuated sweating [upper back sweat rate (SR)] and skin blood flow (SkBF) responses. We evaluated the hypothesis that heat loss is not altered during exercise-rest cycles (ER). Ten male participants randomly performed four 120-min trials: 1) 60-min Ex and 60-min recovery (60ER); 2) 3 × 20-min Ex separated by 20-min recoveries (20ER); 3) 6 × 10-min Ex separated by 10-min recoveries (10ER), or 4) 12 × 5-min Ex separated by 5-min recoveries (5ER). Exercise was performed at a workload of 130 W at 35°C. Whole body heat exchange was determined by direct calorimetry. Core temperature, SR (by ventilated capsule), and SkBF (by laser-doppler) were measured continuously. Evaporative heat loss (EHL) progressively increased with each ER, such that it was significantly greater (P ≤ 0.05) at the end of the last compared with the first Ex for 5ER (299 ± 39 vs. 440 ± 41 W), 10ER (425 ± 51 vs. 519 ± 45 W), and 20ER (515 ± 63 vs. 575 ± 74 W). The slope of the EHL response against esophageal temperature significantly increased from the first to the last Ex within the 10ER (376 ± 56 vs. 445 ± 89 W/°C, P ≤ 0.05) and 20ER (535 ± 85 vs. 588 ± 28 W/°C, P ≤ 0.05) conditions, but not during 5ER (296 ± 96 W/°C vs. 278 ± 95 W/°C, P = 0.237). In contrast, the slope of the SkBF response against esophageal temperature did not significantly change from the first to the last Ex (5ER: 51 ± 23 vs. 54 ± 19%/°C, P = 0.848; 10ER: 53 ± 8 vs. 56 ± 21%/°C, P = 0.786; 20ER: 44 ± 20 vs. 50 ± 27%/°C, P = 0.432). Overall, no differences in body heat content and core temperature were observed. These results suggest that altered local and whole body heat loss responses do not explain the previously observed greater core temperatures during intermittent exercise.     

Control of cutaneous vascular conductance and sweating during recovery from dynamic exercise in humans.

The purpose of the study was to examine the effect of 1) passive (assisted pedaling), 2) active (loadless pedaling), and 3) inactive (motionless) recovery modes on mean arterial pressure (MAP), skin blood flow (SkBF), and sweating during recovery after 15 min of dynamic exercise. It was hypothesized that an active recovery mode would be most effective in attenuating the fall in MAP, SkBF, and sweating during exercise recovery. Six male subjects performed 15 min of cycle ergometer exercise at 70% of their predetermined peak oxygen consumption followed by 15 min of 1) active, 2) passive, or 3) inactive recovery. Mean skin temperature (T(sk)), esophageal temperature (T(es)), SkBF, sweating, cardiac output (CO), stroke volume (SV), heart rate (HR), total peripheral resistance (TPR), and MAP were recorded at baseline, end exercise, and 2, 5, 8, 12, and 15 min postexercise. Cutaneous vascular conductance (CVC) was calculated as the ratio of laser-Doppler blood flow to MAP. In the active and passive recovery modes, CVC, sweat rate, MAP, CO, and SV remained elevated over inactive values (P < 0.05). The passive mode was equally as effective as the active mode in maintaining CO, SV, MAP, CVC, and sweat rate above inactive recovery. Sweat rate was different among all modes after 8 min of recovery (P < 0.05). TPR during active recovery remained significantly lower than during recovery in the passive and inactive modes (P < 0.05). No differences in either T(es) or T(sk) were observed among conditions. Given that MAP was higher during passive and active recovery modes than during inactive recovery suggests differences in CVC may be due to differences in baroreceptor unloading and not factors attributed to central command. However, differences in sweat rate may be influenced by factors such as central command and mechanoreceptor stimulation.     

Assessment of cutaneous blood flow by using topographical perfusion mapping techniques

The ability of laser Doppler scanning to reproduce the spatialpattern of cutaneous vascular conductance (CVC) in a6.25-cm² area of skin wasevaluated at supine rest (28°C), during thermal stress (cold andheat), and during baroreceptor unloading with 40-mmHg lower bodynegative pressure (LBNP). The spatial pattern of resting CVC wassimilar on 3 different days, varying by 6 ± 3%. During coldstress, 89 ± 2% of the skin area showed a decrease in skin bloodflow (37 ± 2%), whereas heat stress increased CVC in 94 ± 5%of the skin area. During LBNP, the pattern of CVC response was notuniform, and frequency analysis indicated that 47 ± 5% of thepixels showed a reduction in CVC (>1 SE), 28 ± 2% of the skinarea were unaffected, and the remaining 26 ± 5% of the pixels showed some increase in CVC. These data indicate the ability of topographical perfusion mapping to provide quantitative andreproducible information about the spatial distribution of CVC. Inaddition, the site-to-site variability in reflex control of skin bloodflow during LBNP is intriguing and requires more rigorous evaluation.

     

Oral atorvastatin therapy increases nitric oxide-dependent cutaneous vasodilation in humans by decreasing ascorbate-sensitive oxidants

Elevated low-density lipoproteins (LDL) are associated with cutaneous microvascular dysfunction partially mediated by increased arginase activity, which is decreased following a systemic atorvastatin therapy. We hypothesized that increased ascorbate-sensitive oxidant stress, partially mediated through uncoupled nitric oxide synthase (NOS) induced by upregulated arginase, contributes to cutaneous microvascular dysfunction in hypercholesterolemic (HC) humans. Four microdialysis fibers were placed in the skin of nine HC (LDL = 177 ± 6 mg/dl) men and women before and after 3 mo of a systemic atorvastatin intervention and at baseline in nine normocholesterolemic (NC) (LDL = 95 ± 4 mg/dl) subjects. Sites served as control, NOS inhibited, L-ascorbate, and arginase-inhibited+L-ascorbate. Skin blood flow was measured while local skin heating (42°C) induced NO-dependent vasodilation. After the established plateau in all sites, 20 mM ?ngname? was infused to quantify NO-dependent vasodilation. Data were normalized to maximum cutaneous vascular conductance (CVC) (sodium nitroprusside + 43°C). The plateau in vasodilation during local heating (HC: 78 ± 4 vs. NC: 96 ± 2% CVC(max), P < 0.01) and NO-dependent vasodilation (HC: 40 ± 4 vs. NC: 54 ± 4% CVC(max), P < 0.01) was reduced in the HC group. Acute L-ascorbate alone (91 ± 5% CVC(max), P < 0.001) or combined with arginase inhibition (96 ± 3% CVC(max), P < 0.001) augmented the plateau in vasodilation in the HC group but not the NC group (ascorbate: 96 ± 2; combo: 93 ± 4% CVC(max), both P > 0.05). After the atorvastatin intervention NO-dependent vasodilation was augmented in the HC group (HC postatorvastatin: 64 ± 4% CVC(max), P < 0.01), and there was no further effect of ascorbate alone (58 ± 4% CVC(max,) P > 0.05) or combined with arginase inhibition (67 ± 4% CVC(max,) P > 0.05). Increased ascorbate-sensitive oxidants contribute to hypercholesteromic associated cutaneous microvascular dysfunction which is partially reversed with atorvastatin therapy.     

Graded cutaneous vascular responses to dynamic leg exercise

The cutaneous vascular conductance-esophageal temperature (CVC-Tes) relationship was examined at five work loads (75-200 W) in each of four men to find whether there is a role for exercise intensity in the control of skin blood flow (SkBF). Several factors contributed to our evaluation of the CVC-Tes relationship during work. Laser-Doppler velocimetry (LDF) provided a continuous measure of SkBF that is not influenced by underlying muscle blood flow. Local warming to 39 degrees C at the site of measurement of SkBF provided a consistent skin temperature and facilitated observation of changes in LDF. Mean arterial pressure was measured noninvasively once per minute to calculate CVC. Supine exercise minimized baroreceptor-induced cutaneous vasoconstriction. Our major finding was that the internal temperature at which CVC began to rise during exercise (CVC threshold) was graded with work load beyond 125 W (P less than 0.05). In that range the CVC threshold increased by 0.16 degrees C for every increment of 25 W. The CVC threshold was never reached at the highest work load in three of the four subjects. There was no consistent effect of work load on the slope of the CVC-Tes relationship or on the internal temperature at which sweating began during exercise (sweat rate threshold). We conclude that the level of work beyond 125 W affects the CVC-Tes relationship in a graded fashion, principally through shifts in threshold.     

Validity of auscultatory and Penaz blood pressure measurements during profound heat stress alone and with an orthostatic challenge

Despite frequent reporting of blood pressure (BP) during profound passive heat stress, both with and without a hypotensive challenge, the method by which BP is measured often varies between laboratories. It is unknown whether auscultatory and finger BP measures accurately reflect intra-arterial BP during dynamic changes in cardiac output and peripheral resistance associated with the aforementioned conditions. The purpose of this investigation was to test the hypothesis that auscultatory BP measured at the brachial artery, and finger BP measured by the Penaz method, are valid measures of intra-arterial BP during a passive heat stress and a heat-stressed orthostatic challenge, via lower body negative pressure (LBNP). Absolute (specific aim 1) and the change in (specific aim 2) systolic (SBP), diastolic (DBP), and mean BPs (MBP) were compared at normothermia, after a core temperature increase of 1.47 ± 0.09°C, and during subsequent LBNP. Heat stress did not change auscultatory SBP (6 ± 11 mmHg; P = 0.16), but Penaz SBP (-22 ± 16 mmHg; P < 0.001) and intra-arterial SBP (-11 ± 13 mmHg P = 0.017) decreased. In contrast, DBP and MBP did not differ between methods throughout heat stress. Compared with BP before LBNP, the magnitude of the reduction in BP with all three methods was similar throughout LBNP (P > 0.05). In conclusion, auscultatory SBP and Penaz SBP failed to track the decrease in intra-arterial SBP that occurred during the profound heat stress, while decreases in arterial BP during an orthostatic challenge are comparable between methodologies.     

Cutaneous vascular responses to isometric handgrip exercise during local heating and hyperthermia.

The dramatic increase in skin blood flow and sweating observed during heat stress is mediated by poorly understood sympathetic cholinergic mechanisms. One theory suggests that a single sympathetic cholinergic nerve mediates cutaneous active vasodilation (AVD) and sweating via cotransmission of separate neurotransmitters, because AVD and sweating track temporally and directionally when activated during passive whole body heat stress. It has also been suggested that these responses are regulated independently, because cutaneous vascular conductance (CVC) has been shown to decrease, whereas sweat rate increases, during combined hyperthermia and isometric handgrip exercise. We tested the hypothesis that CVC decreases during isometric handgrip exercise if skin blood flow is elevated using local heating to levels similar to that induced by pronounced hyperthermia but that this does not occur at lower levels of skin blood flow. Subjects performed isometric handgrip exercise as CVC was elevated at selected sites to varying levels by local heating (which is independent of AVD) in thermoneutral and hyperthermic conditions. During thermoneutral isometric handgrip exercise, CVC decreased at sites in which blood flow was significantly elevated before exercise (-6.5 +/- 1.8% of maximal CVC at 41 degrees C and -10.5 +/- 2.0% of maximal CVC at 43 degrees C; P < 0.05 vs. preexercise). During isometric handgrip exercise in the hyperthermic condition, an observed decrease in CVC was associated with the level of CVC before exercise. Taken together, these findings argue against withdrawal of AVD to explain the decrease in CVC observed during isometric handgrip exercise in hyperthermic conditions.     

Large differences in peak oxygen uptake do not independently alter changes in core temperature and sweating during exercise

The independent influence of peak oxygen uptake (Vo(? peak)) on changes in thermoregulatory responses during exercise in a neutral climate has not been previously isolated because of complex interactions between Vo(? peak), metabolic heat production (H(prod)), body mass, and body surface area (BSA). It was hypothesized that Vo(? peak) does not independently alter changes in core temperature and sweating during exercise. Fourteen males, 7 high (HI) Vo(? peak): 60.1 ± 4.5 ml·kg?1·min?1; 7 low (LO) Vo(? peak): 40.3 ± 2.9 ml·kg?1·min?1 matched for body mass (HI: 78.2 ± 6.1 kg; LO: 78.7 ± 7.1 kg) and BSA (HI: 1.97 ± 0.08 m2; LO: 1.94 ± 0.08 m2), cycled for 60-min at 1) a fixed heat production (FHP trial) and 2) a relative exercise intensity of 60% Vo(? peak) (REL trial) at 24.8 ± 0.6°C, 26 ± 10% RH. In the FHP trial, H(prod) was similar between the HI (542 ± 38 W, 7.0 ± 0.6 W/kg or 275 ± 25 W/m2) and LO (535 ± 39 W, 6.9 ± 0.9 W/kg or 277 ± 29 W/m2) groups, while changes in rectal (T(re): HI: 0.87 ± 0.15°C, LO: 0.87 ± 0.18°C, P = 1.00) and aural canal (T(au): HI: 0.70 ± 0.12°C, LO: 0.74 ± 0.21°C, P = 0.65) temperature, whole-body sweat loss (WBSL) (HI: 434 ± 80 ml, LO: 440 ± 41 ml; P = 0.86), and steady-state local sweating (LSR(back)) (P = 0.40) were all similar despite relative exercise intensity being different (HI: 39.7 ± 4.2%, LO: 57.6 ± 8.0% Vo(2 peak); P = 0.001). At 60% Vo(2 peak), H(prod) was greater in the HI (834 ± 77 W, 10.7 ± 1.3 W/kg or 423 ± 44 W/m2) compared with LO (600 ± 90 W, 7.7 ± 1.4 W/kg or 310 ± 50 W/m2) group (all P < 0.001), as were changes in T(re) (HI: 1.43 ± 0.28°C, LO: 0.89 ± 0.19°C; P = 0.001) and T(au) (HI: 1.11 ± 0.21°C, LO: 0.66 ± 0.14°C; P < 0.001), and WBSL between 0 and 15, 15 and 30, 30 and 45, and 45 and 60 min (all P < 0.01), and LSR(back) (P = 0.02). The absolute esophageal temperature (T(es)) onset for sudomotor activity was ～0.3°C lower (P < 0.05) in the HI group, but the change in T(es) from preexercise values before sweating onset was similar between groups. Sudomotor thermosensitivity during exercise were similar in both FHP (P = 0.22) and REL (P = 0.77) trials. In conclusion, changes in core temperature and sweating during exercise in a neutral climate are determined by H(prod), mass, and BSA, not Vo(? peak).     

Influence of beta-adrenergic blockade on the control of sweating in humans

To evaluate the role of beta-adrenergic receptors in the control of human sweating, we studied six subjects during 40 min of cycle-ergometer exercise (60% maximal O2 consumption) at 22 degrees C 2 h after oral administration of placebo or nonselective beta-blockade (BB, 80 mg propranolol). Internal temperature (esophageal temperature, Tes), mean skin temperature (Tsk), local chest temperature (Tch), and local chest sweat rate (msw) were continuously recorded. The control of sweating was best described by the slope of the linear relationship between msw and Tes and the threshold Tes for the onset of sweating. The slope of the msw-Tes relationship decreased 27% (P less than 0.01), from 1.80 to 1.30 mg X cm-2 X min-1 X degree C-1 during BB. The Tes threshold for sweating (36.8 degrees C) was not altered as the result of BB. These data suggest that BB modified the control of sweating via some peripheral interaction. Since Tsk was significantly (P less than 0.05) reduced during BB exercise, from a control value of 32.8 to 32.2 degrees C, we evaluated the influence of the reduction in local skin temperature (Tsk) in the altered control of sweating. Reductions in Tch accounted for only 45% of the decrease in the slope of the msw-Tes relationship during BB. Since evaporative heat loss requirement during exercise with BB, as estimated from the energy balance equation, was also reduced 18%, compared with control exercise, we concluded that during BB the reduction in sweating at any Tes is the consequence of both a decrease in local Tsk and a direct effect on sweat gland.     

Oral vitamin C enhances the adrenergic vasoconstrictor response to local cooling in human skin

Local administration of ascorbic acid (Asc) at a supraphysiological concentration inhibits the cutaneous vasoconstrictor response to local cooling (LC). However, whether orally ingesting Asc inhibits the LC-induced vasoconstrictor response remains unknown. The purpose of the present study was to examine the acute influence of oral Asc on the adrenergic vasoconstrictor response to LC in human skin. In experiment 1, skin blood flow (SkBF) was measured by laser-Doppler flowmetry at three sites (forearm, calf, palm). The three skin sites were locally cooled from 34 to 24°C at -1°C/min and maintained at 24°C for 20 min before (Pre) and 1.5 h after (Post) oral Asc (2-g single dose) or placebo supplementation. Cutaneous vascular conductance (CVC) was calculated as the ratio of SkBF to blood pressure and expressed relative to the baseline value before LC. Oral Asc enhanced (P < 0.05) the reductions in CVC in the forearm (Pre, -50.3 ± 3.3%; Post, -57.8 ± 2.2%), calf (Pre, -52.6 ± 3.7%; Post, -66.1 ± 4.3%), and palm (Pre, -46.2 ± 6.2%; Post, -60.4 ± 5.6%) during LC. The placebo did not change the responses at any site. In experiment 2, to examine whether the increased vasoconstrictor response caused by oral Asc is due to the adrenergic system, the release of neurotransmitters from adrenergic nerves in forearm skin was blocked locally by iontophoresis of bretylium tosylate (BT). Oral Asc enhanced (P < 0.05) the reductions in CVC at untreated control sites but did not change the responses at BT-treated sites during LC. In experiment 3, to further examine whether adrenergically mediated vasoconstriction is enhanced by oral Asc, 0.1 mM tyramine was administered using intradermal microdialysis in the forearm skin at 34°C in the Pre and Post periods. Oral Asc increased (P < 0.05) the tyramine-induced reduction in CVC. These findings suggest that oral Asc acutely enhances the cutaneous vasoconstrictor responses to LC through the modification of adrenergic sympathetic mechanisms.     

Active recovery attenuates the fall in sweat rate but not cutaneous vascular conductance after supine exercise.

The purpose of this study was to identify whether baroreceptor unloading was responsible for less efficient heat loss responses (i.e., skin blood flow and sweat rate) previously reported during inactive compared with active recovery after upright cycle exercise (Carter R III, Wilson TE, Watenpaugh DE, Smith ML, and Crandall CG. J Appl Physiol 93: 1918-1929, 2002). Eight healthy adults performed two 15-min bouts of supine cycle exercise followed by inactive or active (no-load pedaling) supine recovery. Core temperature (T(core)), mean skin temperature (T(sk)), heart rate, mean arterial blood pressure (MAP), thoracic impedance, central venous pressure (n = 4), cutaneous vascular conductance (CVC; laser-Doppler flux/MAP expressed as percentage of maximal vasodilation), and sweat rate were measured throughout exercise and during 5 min of recovery. Exercise bouts were similar in power output, heart rate, T(core), and T(sk). Baroreceptor loading and thermal status were similar during trials because MAP (90 +/- 4, 88 +/- 4 mmHg), thoracic impedance (29 +/- 1, 28 +/- 2 Omega), central venous pressure (5 +/- 1, 4 +/- 1 mmHg), T(core) (37.5 +/- 0.1, 37.5 +/- 0.1 degrees C), and T(sk) (34.1 +/- 0.3, 34.2 +/- 0.2 degrees C) were not significantly different at 3 min of recovery between active and inactive recoveries, respectively; all P > 0.05. At 3 min of recovery, chest CVC was not significantly different between active (25 +/- 6% of maximum) and inactive (28 +/- 6% of maximum; P > 0.05) recovery. In contrast, at this time point, chest sweat rate was higher during active (0.45 +/- 0.16 mg.cm(-2).min(-1)) compared with inactive (0.34 +/- 0.19 mg.cm(-2).min(-1); P < 0.05) recovery. After exercise CVC and sweat rate are differentially controlled, with CVC being primarily influenced by baroreceptor loading status while sweat rate is influenced by other factors.     

Active cutaneous vasodilation in resting humans during mild heat stress.

The role of skin temperature in reflex control of the active cutaneous vasodilator system was examined in six subjects during mild graded heat stress imposed by perfusing water at 34, 36, 38, and 40 degrees C through a tube-lined garment. Skin sympathetic nerve activity (SSNA) was recorded from the peroneal nerve with microneurography. While monitoring esophageal, mean skin, and local skin temperatures, we recorded skin blood flow at bretylium-treated and untreated skin sites by using laser-Doppler velocimetry and local sweat rate by using capacitance hygrometry on the dorsal foot. Cutaneous vascular conductance (CVC) was calculated by dividing skin blood flow by mean arterial pressure. Mild heat stress increased mean skin temperature by 0.2 or 0.3 degrees C every stage, but esophageal and local skin temperature did not change during the first three stages. CVC at the bretylium tosylate-treated site (CVC(BT)) and sweat expulsion number increased at 38 and 40 degrees C compared with 34 degrees C (P < 0.05); however, CVC at the untreated site did not change. SSNA increased at 40 degrees C (P < 0.05, different from 34 degrees C). However, SSNA burst amplitude increased (P < 0.05), whereas SSNA burst duration decreased (P < 0.05), at the same time as we observed the increase in CVC(BT) and sweat expulsion number. These data support the hypothesis that the active vasodilator system is activated by changes in mean skin temperature, even at normal core temperature, and illustrate the intricate competition between active vasodilator and the vasoconstrictor system for control of skin blood flow during mild heat stress.     

Cerebral leucine uptake and protein synthesis in the near-term ovine fetus: relation to fetal behavioral state

To investigate quantitatively how sweating and cutaneous blood flow responses at the onset of dynamic exercise are affected by increasing exercise intensity in mildly heated humans, 18 healthy male subjects performed cycle exercise at 30, 50, and 70% of maximal O2 uptake (VO2 max) for 60 s in a warm environment. The study was conducted in a climatic chamber with a regulated ambient temperature of 35 degrees C and relative humidity of 50%. The subjects rested in the semisupine position in the chamber for 60 min, and then sweating rate (SR) and skin blood flow were measured during cycle exercise at three different intensities. Changes in the heart rate, rating of perceived exertion, and mean arterial blood pressure were proportional to increasing exercise intensity, whereas esophageal and mean skin temperatures were essentially constant throughout the experiment. The SR on the chest, forearm, and thigh, but not on the palm, increased significantly with increasing exercise intensity (P < 0.05). The mean SR of the chest, forearm, and thigh increased 0.05 mg.cm-2.min-1 with an increase in exercise intensity equivalent to 10% VO2 max. On the other hand, the cutaneous vascular conductance (CVC) on the chest, forearm, and palm decreased significantly with increasing exercise intensity (P < 0.05). The mean CVC of the chest and forearm decreased 5.5% and the CVC on the palm decreased 8.0% with an increase in exercise intensity equivalent to 10% VO2 max. In addition, the reduction in CVC was greater on the palm than on the chest and forearm at all exercise intensities (P < 0.01). We conclude that nonthermal sweating and cutaneous blood flow responses are exercise intensity dependent but directionally opposite at the onset of dynamic exercise in mildly heated humans. Furthermore, cutaneous blood flow responses to increased exercise intensity are greater in glabrous (palm) than in nonglabrous (chest and forearm) skin.     

Influence of the menstrual cycle on the sweating response measured by direct calorimetry in women exposed to warm environmental conditions

The whole body sweating response was measured at rest in eight women during the follicular (F) and the luteal (L) phases of the menstrual cycle. Subjects were exposed for 30-min to neutral (N) environmental conditions [ambient temperature (Ta) 28 degrees C] and then for 90-min to warm (W) environmental conditions (Ta, 35 degrees C) in a direct calorimeter. At the end of the N exposure, tympanic temperature (Tty) was 0.18 (SEM 0.06) degrees C higher in the L than in the F phase (P less than 0.05), whereas mean skin temperature (Tsk) was unchanged. During W exposure, the time to the onset of sweating as well as the concomitant increase in body heat content were similar in both phases. At the onset of sweating, the tympanic threshold temperature (Tty,thresh) was higher in the L phase [37.18 (SEM 0.08) degrees C] than in the F phase [36.95 (SEM 0.07) degrees C; P less than 0.01]. The magnitude of the shift in Tty,thresh [0.23 (SEM 0.07) degrees C] was similar to the L-F difference in Tty observed at the end of the N exposure. The mean skin threshold temperature was not statistically different between the two phases. The slope of the relationship between sweating rate and Tty was similar in F and L. It was concluded that the internal set point temperature of resting women exposed to warm environmental conditions shifted to a higher value during the L phase compared to the F phase of the menstrual cycle; and that the magnitude of the shift corresponded to the difference in internal temperature observed in neutral environmental conditions between the two phases.     

Exercise thermoregulation after prolonged wakefulness

The effect of 33 h of wakefulness on the control of forearm cutaneous blood flow and forearm sweating during exercise was studied in three men and three women. Subjects exercised for 30 min at 60% peak O2 consumption while seated behind a cycle ergometer (Ta = 35 degrees C, Pw = 1.0 kPa). We measured esophageal temperature (Tes), mean skin temperature, and arm sweating continuously and forearm blood flow (FBF) as an index of skin blood flow, twice each minute by venous occlusion plethysmography. During steady-state exercise, Tes was unchanged by sleep loss. The sensitivity of FBF to Tes was depressed an average of 30% (P less than 0.05) after 33 h of wakefulness with a slight decrease (-0.15 degrees C, P less than 0.05) in the core temperature threshold for vasodilatory onset. Sleep loss did not alter the Tes at which the onset of sweating occurred; however, sensitivity of arm sweating to Tes tended to be lower but was not significant. Arm skin temperature was not different between control and sleep loss experiments. Reflex cutaneous vasodilation during exercise appeared to be reduced by both central and local factors after 33 h of wakefulness.