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John B. Pierce Laboratory and Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06515
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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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 
-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°C (SE) at control and vasodilator-only skin sites, respectively,
and increased to 0.44 ± 0.10 and 0.50 ± 0.10°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 circulation; sweating; blood pressure
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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THE CUTANEOUS
CIRCULATION is considered to be primarily an efferent arm of
thermoregulatory reflexes (28), but it is also known to
respond to several nonthermoregulatory demands (7, 32). Under resting conditions considerable evidence
supports (3, 11, 20, 29, 34) the hypothesis that skin
blood flow is modulated by baroreceptor unloading [i.e., lower body negative pressure (LBNP) or upright tilting]. For example, Kellogg et
al. (11) showed significant reductions in cutaneous
vascular conductance (CVC) during 3 min of 40 mmHg LBNP. More
importantly, Kellogg et al. were able to demonstrate that during
resting heat stress that baroreceptor unloading also caused a
withdrawal of active cutaneous vasodilation. A limited number of
studies have provided conflicting results, leading some researchers to
argue (36, 37) that the reflex vasoconstriction during
LBNP is mediated by thermoregulatory reflexes responding to a change in
skin temperature, presumably produced by air currents produced within
the LBNP box. It is unclear what factors contribute to the observed
discrepancy in the CVC response to LBNP at rest. Recent observations
from our laboratory point to significant spatial heterogeneity in the CVC response to 40 mmHg LBNP (17), which may contribute
to this controversy.
Baroreflex control of skin blood flow during dynamic exercise has also been examined. In earlier work (20), our laboratory tested the hypothesis that baroreceptor unloading during dynamic exercise limited cutaneous vasodilation and sweating and that this effect was rapidly reversed after removal of the LBNP stimulus. In these experiments, venous occlusion plethysmography was used to measure changes in forearm blood flow and arterial blood pressure was used to calculate forearm vascular conductance (FVC) as an index of changes in skin blood flow (38). During exercise with LBNP, the limitation in cutaneous vasodilation was quickly reversed when LBNP was removed and, as exercise continued, the rate of rise of FVC per unit increase in esophageal temperature reached a level expected for exercise without LBNP. This type of response was indicative of a neurally mediated interaction and would not be expected if the limitation in cutaneous vasodilation was due to some time-dependent factor, such as a circulating vasoactive hormone. In addition, on the basis of existing models of thermoregulatory control of skin blood flow (25, 40, 41), the small changes in skin temperature that occurred during application of LBNP could not explain the reflex response in the periphery (19). One limitation to our interpretation of these data was the use of changes in forearm blood flow to evaluate thermoregulatory control of active cutaneous vasodilation. Using venous occlusion plethysmography, we were unable to separate the contributions of increased vasoconstrictor activity and vasodilator withdrawal on the cutaneous vasodilator response to exercise. The present study represents the logical extension of our laboratory's initial work and combines the direct measurement of skin blood flow using laser-Doppler velocimetry and local blockade of the cutaneous sympathetic vasoconstrictor system using local iontophoresis of bretylium tosylate (10) to examine the impact of baroreceptor unloading on the thermoregulatory control of active cutaneous vasodilation during exercise. We tested the hypothesis that baroreceptor unloading during dynamic exercise limits cutaneous vasodilation by withdrawal of active vasodilator activity.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Seven healthy adults (4 men, 3 women) volunteered to participate in this study. All volunteers were in good health, and each subject was thoroughly acquainted with all aspects of the experiment before written informed consent was obtained. All experimental protocols were approved by the institutional ethics committee. The physical characteristics of the subjects were age 25 ± 1 yr, body weight 67.8 ± 4.4 kg, and height 169 ± 4 cm. Each subject performed two experimental protocols, on separate days spaced 1-4 wk apart, at an ambient temperature of 28°C (<35% relative humidity, minimal air speed), and all protocols were performed with the subjects in the supine position. Female subjects were tested during the first 5 days of the menstrual cycle.
On each experimental day, the subject arrived at the laboratory at 0800 and ingested 500 ml of water to ensure similar hydration status between
trials. Next, an area of skin (6.2 cm2) on the
ventral forearm devoid of any superficial veins was chosen for
application of iontophoresis and measurement of skin blood flow by
using laser-Doppler velocimetry (635-nm laser, Moor Instruments, Devon,
UK). A LectroPatch (General Medical, Los Angeles, CA)
iontophoresis unit, consisting of two adjacent yet separate treatment
compartments, was used. In each treatment compartment, a
3.1-cm2 treatment pad was placed and soaked with 1.5 ml of
either bretylium tosylate (100 mM) or vehicle (pure water). The
iontophoresis protocol consisted of 20 min at a current density of 160 µA/cm2 followed by 20 min at a current density of 80 µA/cm2. Effective -adrenergic blockade was tested 120 min after iontophoresis by cooling the entire skin surface (except
feet, hands, head, and the local skin site on the forearm) and
recording the skin blood flow and arterial blood pressure. Mean skin
temperature was first held at 34°C with the aid of a liquid-perfused
garment covering most of the body surface and perfused with water at
34°C. The water perfusing the garment was rapidly changed to 2°C,
and skin cooling continued for 3 min. Changes in CVC at each skin site
were calculated by dividing the laser-Doppler flux reading by arterial
blood pressure measured in noninvasively using an automated brachial
artery cuff (Colin STBP model 780B, Aichi, Japan). A second cold stress
test was performed at the end of the experiment to verify persistent
-adrenergic blockade. The skin site at which -adrenergic blockade
occurred is referred to as the vasodilator only site.
After verification of blockade, the subject removed the liquid-perfused
garment, swallowed an esophageal thermocouple, and assumed the supine
position with the lower part of the body in the LBNP box. The waist was
sealed at the level of the iliac crest with a flexible neoprene dam.
The LBNP box was designed to allow supine exercise on a Collins
electronically braked cycle ergometer placed within the box. The cycle
was located on an adjustable slide to accommodate variations in leg
length, and the box was constructed such that during a pedal cycle the
fully extended leg was never more than 20° above or below the
horizontal plane of the hip. Each experiment consisted of 30 min of
supine rest, 5 min of preexercise control data collection, and 30 min
of continuous supine exercise at an exercise intensity of 119 ± 8 W. This exercise intensity was identified as the power requirement
eliciting a heart rate of 125 beats/min during a graded submaximal
supine exercise protocol, performed on a separate day. LBNP was applied either 1) 2 min before the onset of exercise and maintained
for the first 15 min of exercise or 2) during the last 15 min of exercise (Fig. 1). Experimental
protocols were performed at the same time of day for each subject
spaced a minimum of 2 days apart, and the order in which LBNP was
applied during exercise was determined by a balanced crossover design.
Body core temperatures (esophageal and 7 skin sites) and local chest
sweat rate were measured once every 30 s, whereas heart rate and
arterial blood pressures were measured once every minute during the
experimental protocol.
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Physiological measurements. Systolic (SBP) and diastolic (DBP) blood pressures were measured noninvasively with a Colin STPB monitor. Mean arterial blood pressure (MAP) was calculated as (SBP + 2 × DBP)/3. Skin blood flow was measured by laser-Doppler velocimetry. In all experiments, we measured skin blood flow simultaneously at a control and vasodilator-only skin site. At these sites, the laser-Doppler flow probe was mounted on the skin with a lightweight servo-controlled heater. Local skin temperature at the probe holder was controlled at 34°C during the experimental protocol. In several of the experiments, but not all, a third skin site on the ventral forearm that was not exposed to iontophoresis and did not have local skin temperature controlled (untreated site) was also monitored. CVC was calculated from 30-s averages of laser-Doppler flux readings throughout the experimental protocol by dividing laser-Doppler flux readings in volts by MAP. At the end of each experiment, local skin temperature at the control and vasodilator-only skin sites was raised to 43-44°C. After 30 min of local heating, peak CVC was determined. The subject exited the LBNP box and again put on the liquid-perfused garment. After a 10- to 15-min baseline period, a second cold-stress test was performed to verify persistent adrenergic blockade (Fig. 1). Peak CVC was not determined at the untreated skin sites. Local chest sweat rate was measured using a dew-point hygrometry system with a 12.4-cm2 capsule.
Body core temperature was measured from a thermocouple placed at a depth determined by passing the thermocouple through the nose a distance of one-fourth the subject's height (40). Skin temperatures were measured with thermocouple mounted across acrylic rings, which were attached to the skin so that the outer surface of the thermocouple was freely exposed to the air. Mean skin temperature (Tsk) was calculated twice per minute from temperatures at seven skin sites according to the equation
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Data and statistical analysis. CVC at the control and vasodilator-only sites are reported as a percentage of peak. The threshold esophageal temperature for cutaneous vasodilation was defined as the esophageal temperature at which there was an increase in CVC, characterized by rapid increases in CVC over three consecutive measurements. Thermal sensitivity was defined by the slope of the linear portion of the CVC-esophageal temperature relationship. The linear portion of the data was selected by visual inspection, and slopes were determined by least squares linear regression analysis. The area under the curve (AUC) was determined for the first 15 min of exercise and the final 15 min of exercise for mean skin temperature, esophageal temperature, local sweat rate, and CVC. The baseline level for calculation of the AUC was the mean resting value before exercise and the value right before application or removal of LBNP. The AUC represents the integrated response of these thermoregulatory parameters during these 15-min periods of exercise with and without LBNP.
Physiological variables were compared by using ANOVA for repeated measures (LBNP on or off), and pairwise comparisons between exercise protocols were performed at specific times (control, 5, 10, 15, 20, 25, and 30 min of exercise) using Tukey's minimum significant difference method with the level of significance set at P < 0.05. In addition, we estimated the overall effect of LBNP on thermoregulatory function by comparing the AUC of the increase in esophageal temperature, CVC, and local chest sweat rate as a function time using paired t-test. All values are presented as means ± SE of 7 subjects.| |
RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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-Adrenergic blockade.
Application of cold stress induced a significant reduction in CVC at
the control skin site before (13.3 ± 1.5 to 6.0 ± 0.1% peak CVC; P < 0.05) and after (54.5 ± 4.9 to
45.8 ± 5.4% peak CVC; P < 0.05) the
experimental protocol. Iontophoresis of bretylium blocked the
cold-induced reduction in CVC before (12.1 ± 2.3 to 11.1 ± 2.0% peak CVC) and after exercise (56.9 ± 6.5 to 53.3 ± 6.8% peak CVC), demonstrating effective and persistent sympathetic vasoconstrictor blockade at these skin sites. Application of LBNP before exercise did not produce any significant change in resting CVC
at either control or vasodilator-only sites.
Thermal signals.
The body temperature response to dynamic exercise with and without LBNP
is shown in Figs. 2 and
3. Overall, ANOVA identified a
significant time-LBNP interaction for both mean skin temperature (F value = 11.52, P < 0.05) and
esophageal temperature (F value = 12.89, P < 0.05) when comparing the two exercise protocols. Mean skin temperature was similar at rest before exercise without LBNP
(33.8 ± 0.2°C) and with LBNP (34.0 ± 0.2°C). One-way
ANOVA for repeated measures of the LBNP off/on condition did not
identify any significant effect of time on mean skin temperature
(F = 2.07). In the LBNP on/off condition, one-way ANOVA
for repeated measures indicated that mean skin temperature varied with
time (F = 8.07, P < 0.05) but that no
significant changes in mean skin temperature occurred within the first
15 min of exercise. At 15 min of exercise with LBNP mean skin
temperature averaged 33.8 ± 0.1°C and increased slightly to
34.3 ± 0.2 and 34.4 ± 0.1°C (P < 0.05)
after LBNP was removed at 25 and 30 min of exercise, respectively.
Figure 3 illustrates the impact of exercise and LBNP on the seven local skin sites. These data consistently show that the skin temperatures during the initial 15 min of exercise are similar with and without LBNP. Figure 3 identifies changes in local skin temperature relative to
the 15-min time point of exercise when LBNP is either applied or
removed. There are clear reductions in local skin temperatures after
application of LBNP. However, those skin sites that would be most
affected by a airflow caused by a leak in the LBNP box (thigh, calf,
flank) did not demonstrate any significant change in skin temperature.
In contrast, those skin sites located some distance from any potential
air leaks showed consistent reductions in temperature (shoulder and
chest).
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Cutaneous vasodilation. The magnitude of cutaneous dilation at control skin sites during the first 15 min of exercise was similar with and without LBNP (area under the time-CVC curves averaged 286 ± 54 and 247 ± 35% peak · min, respectively) and at vasodilation-only sites (AUC = 268 ± 63 and 153 ± 31% peak · min, respectively). This similarity occurred despite that fact that the primary thermal drive for vasodilation, esophageal temperature, was always greater during exercise with LBNP than without. Between 15 and 30 min of exercise, the rise in CVC at control sites was greater when LBNP was removed (AUC = 177 ± 50% peak · min) than with LBNP applied (AUC = 39 ± 38% peak · min; P < 0.05). A similar trend was seen in the vasodilation-only sites (AUC = 138 ± 38 and 43 ± 72% peak · min, respectively); however, this difference was not statistically significant. The rise in CVC with removal of LBNP occurred in the face of a minimal change in esophageal temperature.
During exercise, vasodilation in the skin occurred after a given increase in esophageal temperature and the increase in esophageal temperature required to elicit dilation was always higher with LBNP than without. The esophageal temperature threshold for vasodilation for each subject is listed in Table 1. Figure 4 illustrates the stimulus response characteristics of CVC and esophageal temperature during dynamic exercise with and without LBNP at the control (top), vasodilation only (middle), and untreated (bottom) skin sites. During exercise without LBNP, the increase in esophageal temperature required to elicit vasodilation averaged 0.25 ± 0.08 and 0.31 ± 0.10°C at control and vasodilation-only skin sites, respectively. During exercise with LBNP, the increase in esophageal temperature required to elicit vasodilation was higher 0.44 ± 0.10 and 0.50 ± 0.10°C for control and vasodilation-only sites, respectively (P < 0.05). The delay in cutaneous vasodilation was slightly higher in the vasodilation-only skin site than in the control site (P < 0.05) regardless of LBNP. Measurements taken from untreated skin sites in 9 of 14 experiments showed delays in vasodilation consistent with the observations at the control skin sites. Representative data from one subject are shown in Fig. 4.
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Thermal sweating.
Application of LBNP during the first 15 min of exercise caused a delay
in the onset of sweating. The increase in esophageal temperature
required to elicit sweating averaged 0.39 ± 0.10 and 0.20 ± 0.10°C (P < 0.05) with and without LBNP,
respectively. Application of LBNP did not influence the slope of the
linear relationship between local chest sweating and esophageal
temperature, which was 2.44 ± 0.63 and 2.44 ± 0.91 mg · min
1 · cm2 · °C1.
Figure 5 illustrates the mean response of
all seven subjects, and Table 1 lists the esophageal temperature
threshold for sweating for each subject. After 15 min of exercise, LBNP
was either applied or removed. Figure 5 illustrates that the
application of LBNP caused a slight rightward shift in the local cheat
sweat rate-esophageal temperature relationship but did not attenuate
the rate of rise of sweating per unit increase in body core
temperature. The transition from exercise without to exercise with LBNP
produced changes in the local cheat sweat rate-esophageal temperature
relationship. The changes in sweat rate paralleled those of skin blood
flow, but the adjustment in sweat rate appeared to require more time than CVC.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Our laboratory previously demonstrated that, during exercise with LBNP, the limitation in cutaneous vasodilation was quickly reversed when LBNP was removed and that, as exercise continued, the rate of rise of FVC per unit increase in esophageal temperature reached a level expected for exercise without LBNP (19). This type of response was indicative of a neurally mediated interaction and would not be expected if the limitation in cutaneous vasodilation was due to some time-dependent factor, such as a circulating vasoactive hormone. In the present study, we used the highly successful model of Kellogg et al. (10) to isolate the sympathetic vasodilator system by iontophoresis of bretylium tosylate on the skin to eliminate active cutaneous vasoconstrictor activity. The present data provide substantial support for the hypothesis that the interaction of baroreceptors on thermoregulatory responses during exercise represents modulation of active cutaneous vasodilation system. In addition, we confirmed that baroreceptor unloading during exercise also attenuates local chest sweating. These two observations suggest that there is a common site of interaction, proximal to the effector organ, between blood pressure and thermoregulatory reflexes.
Baroreceptor modulation of cutaneous vasodilation during exercise. Our data support the observations by Kellogg et al. (11, 12) and Crandall et al. (3) that skin blood flow is modulated by baroreceptor unloading. In addition, baroreceptor unloading influenced the esophageal temperature threshold for cutaneous vasodilation to a similar degree in control and vasodilation-only skin sites. These data emphasize the primary role of a withdrawal of active vasodilator activity in limiting the cutaneous vasodilator response to dynamic exercise. An intriguing observation was that the vasodilation-only skin sites showed a small yet significantly greater delay in the cutaneous vasodilator threshold compared with the control sites. This observation suggests a possible role of cutaneous sympathetic adrenergic nerves in the initiation of cutaneous vasodilation during exercise.
During the first 15 min of exercise, we can evaluate the impact of LBNP on active cutaneous vasodilation. During this period, no significant changes in mean skin temperature occur during exercise with or without LBNP. Small differences in mean skin temperature were identified between trials; however, these were small and in wrong direction such that mean skin temperature was higher with application of LBNP than without. Thus it is unlikely that mean skin temperature or any change in mean skin temperature as a result of application of LBNP could account for the shift in vasodilator threshold or diminished cutaneous vasodilation during this first 15 min of exercise. At 15 min of exercise, the application or removal of LBNP did produce some changes in mean skin temperature. It is possible that these changes in skin temperature contribute, in part, to the rapid adjustments in CVC during the transition associated with LBNP on or off, especially in the control skin sites with an intact sympathetic-adrenergic vasoconstrictor system. Our interpretation is based on
the premise that both an increase in sympathetic vasoconstrictor
activity and withdrawal of active vasodilator activity contribute to
the reduction in skin blood flow during LBNP. The changes in CVC at
skin sites devoid of the active vasoconstrictor system
(vasodilation-only skin sites) should be immune to a thermally mediated
reflex acting via the sympathetic vasoconstrictor nerves. In addition,
it is unlikely that the changes in local skin temperature were caused
by an air leak because those local skin sites in close proximity to the
waist seal showed the least amount of temperature change compared with
more distant skin sites. The magnitude of change in mean skin
temperature was quite small (range 0.25-0.45°C), and the
available literature (39-41) indicates that this
small change in mean skin temperature will have a minimal impact on the
esophageal temperature-skin blood flow relationship. Vissing
(35) claims that the skin blood flow response to LBNP is
the result of thermoregulatory reflexes responding to changes in body
temperature as air leaks around the waist seal, producing a change in
local skin temperature. This claim is based on sham LBNP experiments in
which air was deliberately leaked around the waist to induce
significant changes in skin temperature. When these temperature changes
were blunted by heating the skin, the vasoconstrictor response was also
blocked. It is important to note that these sham LBNP experiments do
not demonstrate that the decrease in CVC during LBNP is actually due to
a thermoregulatory reflex. Rather, the sham LBNP experiments simply
demonstrate that, if you cool the skin, you get reflex vasoconstriction. In addition, the studies by Kellogg et al. (11, 12) used skin heating to 38°C during LBNP, which would
minimize skin cooling during LBNP.
It is well known that skin cooling produces reflex cutaneous
vasoconstriction; however, local skin cooling (or heating) can also
impact active cutaneous vasodilation. Wenger et al. (38) and Pérgola et al. (25) provide evidence to support
the hypothesis that changes in skin temperature modulate vasodilator
activity in the skin. However, the data in Fig. 4 and 5 illustrate a
shift in the thermoregulatory control of skin blood flow and sweating with LBNP that occurred during the first 15 min of exercise when skin
temperatures were quite similar. We conclude that the impact of LBNP on
thermoregulatory control of skin blood flow and sweating occurs
primarily because of baroreceptor unloading.
In earlier work baroreceptor unloading reduced the slope of the
FVC-esophageal temperature during dynamic exercise (19). However, we found no such reduction in the slope of the CVC-esophageal temperature relationship with application of LBNP (Fig. 3). One possible explanation of this difference is that reduction in the slope
of the FVC-esophageal temperature relationship during baroreceptor unloading reflects an augmented impact of baroreceptor unloading on
forearm blood flow but that this impact is directed primarily toward
skeletal muscle. This is unlikely because the contribution of
forearm muscle blood flow to the FVC-esophageal temperature relationship is limited. A more likely interpretation is that heterogeneity in the skin blood flow response to baroreceptor unloading
(14) resulted in similar slopes of CVC-esophageal temperature relationship with and without LBNP.
Baroreflex modulation of sweating. An important finding of this study was the greater increase in esophageal temperature required to elicit sweating during exercise with baroreceptor unloading than without, but no significant effect of LBNP on the slope of the local chest sweat rate-esophageal temperature relationship was found. These data are in contrast to our laboratory's earlier work that reported some delay in the esophageal threshold for sweating with a reduction in the slope of the local chest sweat rate-esophageal temperature relationship (19). Our laboratory previously reported that small differences in resting body core temperature can influence determination of thermoregulatory thresholds. For this reason, we describe the thermoregulatory threshold as the increase in resting esophageal temperature required to elicit vasodilation or sweating (18, 21). Reanalysis of the earlier data provided results consistent with the present analysis showing that the increase in esophageal temperature required to elicit local chest sweating averaged 0.15 ± 0.05°C without LBNP and increased to 0.30 ± 0.08°C with LBNP (P < 0.05). Also, in the earlier study, our laboratory observed three individuals who showed little or no sweating during exercise with LBNP, it is likely these responses led to the average reduction in the slope of the local chest sweat rate-esophageal temperature relationship. In the present study, none of the subjects demonstrated such dramatic attenuation of sweating during exercise with LBNP and no significant change in sweat sensitivity was observed. In general, the results of the present study in combination with our laboratory's earlier results (19) provide considerable support for the statement that baroreceptor unloading during exercise resulted in a lower local sweat rate at any given esophageal temperature.
Sympathetic nerve recordings from sudomotor fibers show cardiac rhythmicity, indicating that changes in blood pressure may act to modulate sweat gland activity (1). Solak et al. (30) showed that local sweat rate was attenuated during application of LBNP but concluded that the pattern of response was too slow to be explained by a neurally mediated reflex and attributed the reduction in local sweating to the action of a some circulating agent, possibly arginine vasopressin. The delay in sweating response might be expected because some lag time associated with the change in neural drive to the sweat gland and the secretion of fluid into the secretory coil and the eventual alteration in the luminal hydrostatic pressure gradient is required for sweat expulsion. Alternatively, it is possible that some time-dependent factor was contributing to the response. It is more reasonable to assume that the delay in sweat gland response is due to some periglandular neuromodulator substance (i.e., norepinephrine, vasoactive intestinal peptide, or calcitonin gene-related peptide) (31) that will modulate the responsiveness of the sweat gland to rapid changes in sympathetic sudomotor activity. It was originally proposed that cutaneous vasodilation and sweating were closely linked (4). Recent evidence has been able to demonstrate conditions where these two systems dissociate (12, 13). However, the present data support the concept that these two thermoregulatory processes are functionally linked during dynamic exercise and are modulated in a similar manner by baroreceptor unloading. Whether this similarity in response is due to an alteration in some final common pathway (i.e., sudomotor nerve activity) requires further study.Limitations. Our interpretation of the present data is based on the premise that the small changes in skin temperature during baroreceptor unloading with application of LBNP are not due to peripheral cooling, which might elicit a thermoregulatory reduction in skin blood flow. Thermoregulatory effector organ responses to thermal stimuli depend on sensory information from both the core and peripheral (skin) thermoreceptors (6). Thermal sensors in the skin provide input to the hypothalamic temperature regulatory centers that act to change skin blood flow via changes in cutaneous sympathetic adrenergic tone or modulation of the drive for active cutaneous vasodilation (2, 22, 39-41). Classic studies have indicated that the contribution of core and skin temperature to thermoregulatory control of active cutaneous vasodilation is in a ratio of ~20:1 (core to skin) (39-41). These concepts predict that fairly large changes in skin temperatures are required to induce substantial changes in skin blood flow (or sweating) when core temperature is normothermic (37°C). For example, a 5°C increase in mean skin temperature produces only a slight increase in CVC (25), whereas a decrease in skin temperature of similar magnitude produces only 10-15% reduction in CVC (3, 8, 11, 26). During exercise when body core temperature is elevated, changes in skin temperature can produce more marked responses in CVC. An important question in this study is whether the small change in skin temperature during combined exercise and LBNP (0.2-0.4°C) is caused by skin cooling, thereby initiating a thermoregulatory-mediated reduction in skin blood flow, or is the result of baroreceptor-mediated reduction in skin blood flow.
Because of thermal inertia in the cutaneous tissue, a large temperature gradient (from ambient to skin) is required to induce rapid changes in skin temperature. For example, to achieve a rate of change in skin temperature in the order of 2.0°C/min would require that ambient air temperature decrease from 40 to 27°C at a rate of 2°C/min (15, 16). In the present study, the rate of change of skin temperature during exercise with application of LBNP exercise was ~0.16°C/min. It is unclear how skin temperature could change at this rate when ambient temperature is constant, and the cooling must be attributed to a modest increase airflow (presumably due to a leaky around the waist seal) and some evaporative cooling. In addition, our experimental conditions were such that mean skin temperature during rest and exercise was always above 33°C. Cutaneous cold sensors exhibit maximal static activity between 25 and 33°C with peak discharge rates during cooling proportional to the rate of change in skin temperature (27). Two factors would minimize the role of skin cooling during LBNP in producing significant cutaneous vasoconstriction. First, average mean skin temperature was above the general range of maximal static activity of most cutaneous cold sensors. Second, magnitude of decrease in mean skin temperature (less than0.5°C) and the maximal rate of change in skin temperature
during LBNP (0.16°C/min) provide limited stimulus to these cold
receptors at an average mean skin temperature of 34°C. If skin
cooling did contribute to the decrease in skin temperature, it is
unlikely that the small reduction in skin temperature would
significantly activate cold thermosensors in the skin.
The decrease in mean skin temperature during exercise with LBNP is more
likely the result of reductions in skin blood flow and a redistribution
of the heat between core and skin. Spontaneous bursts of skin
sympathetic nerve activity (SSNA) are associated with transient
reductions in skin blood (24). Despite the transient nature of the SSNA and accompanying skin blood flow responses, a drop
in local skin temperature is also observed. The drop in skin
temperature is delayed by 10-20 s (from the time of the SSNA burst) and lasts ~2-3 min. This is consistent with the timing between changes in CVC and skin temperature as shown in Fig. 2. During
the first 15 min of exercise, skin temperature decreased at the onset
of exercise in both groups (with and without LBNP), presumably due to
an exercise-induced cutaneous vasoconstriction (21, 33).
When cutaneous dilation occurred during exercise without LBNP, skin
temperature rose (0.2°C). During exercise with LBNP cutaneous
vasodilation occurred at a later time and the magnitude of the
vasodilation was limited. In this case, skin temperature did not rise
but remained stable (no further decline). Our interpretation is
consistent with the idea that LBNP limited cutaneous dilation and thus
the rise in skin temperature during the first 15 min of exercise.
During exercise application of LBNP at 15 min fell to a nadir within
2-2.5 min, whereas the nadir in mean skin temperature lagged
slightly (
3.5 min) (Fig. 2). This pattern was similar for control
and vasodilator-only skin sites, indicating that changes in CVC were
acting to change skin temperature. In support of this conclusion, Fig.
3 shows significant changes in local skin temperature occur at sites
that are distant from those most vulnerable to airflow-induced cooling.
Another example of the redistribution of heat between the core and skin
is seen during the LBNP off-transient. In this case, dilation of
cutaneous blood vessels after removal of LBNP was accompanied by a
significant reduction in skin temperature in the calf and thigh as the
warm blood in the lower limbs was redistributed to the upper limbs.
Overall, the data support the idea that changes in skin blood flow
(either through changes in vasoconstrictor or active cutaneous
vasodilator activity) and a redistribution of heat are the most
plausible explanations for the changes in skin temperature seen during
exercise with or without LBNP.
Summary. We were unable to identify baroreceptor-mediated reductions in skin blood flow at rest. However, baroreceptor unloading clearly attenuated thermoregulatory control of skin blood flow and local chest sweat rate during dynamic exercise. Baroreceptor unloading limited cutaneous vasodilation during dynamic exercise and was immediately reversed after removal of the blood pressure challenge. A similar limitation in local chest sweating indicates a generalized modulation of thermoregulatory reflexes by baroreceptors, including the active cutaneous vasodilator system. In view of data from several studies (9-12, 14, 20) the response in the skin is due primarily to withdrawal of active cutaneous vasodilator drive. This interaction is not the result of peripheral competition between vasodilator and vasoconstrictor activity but likely occurs somewhere within the central nervous system.
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ACKNOWLEDGEMENTS |
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This study was supported by National, Heart, Lung, and Blood Institute Grant HL-39818.
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FOOTNOTES |
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Address for reprint requests and other correspondence: G. Mack, John B. Pierce Laboratory, 290 Congress Ave., New Haven, CT 06515 (E-mail: mack{at}jbpierce.org).
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 13 December 1999; accepted in final form 22 November 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
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O2,
oxygen uptake; CVC, cutaneous vascular conductance.
Significant difference between 15 min, P < 0.05.
