J Appl Physiol 100: 1692–1701, 2006;
doi:10.1152/japplphysiol.01124.2005.
Invited Review
A Physiological Systems Approach to Human
and Mammalian Thermoregulation
HIGHLIGHTED TOPIC
Neural control and mechanisms of eccrine sweating during
heat stress and exercise
Manabu Shibasaki,1 Thad E. Wilson,2 and Craig G. Crandall3,4
1
Department of Environmental Health, Nara Women’s University, Nara, Japan; 2Departments of Pharmacology
and Physiology and of Dermatology, Drexel University College of Medicine, Philadelphia, Pennsylvania;
3
Institute for Exercise and Environmental Medicine, Presbyterian Hospital of Dallas, Dallas; and
4
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas
thermoregulation; hyperthermia; dehydration; cholinergic nerve; perspiration;
sweat gland
BRIEF HISTORY OF THE STUDY OF SWEATING
Heat dissipation is vital for mammalian survival during
exercise and heat stress. In humans, an important mode of heat
dissipation occurs through evaporation of sweat secreted from
eccrine glands. The first description of sweating dates back to
the ancient Greeks (97). In Aristotle’s writings entitled Parts of
Animals, as translated by Peck (6), he summarized their understanding of sweating as follows:
The blood vessels get progressively smaller as they go on
until their channel is too small for the blood to pass through.
But although the blood cannot get through them, the residue of
the fluid moisture, which we call sweat can do so, and this
happens when the body is thoroughly heated and the blood
vessels are open widely at their mouth.
Although in the 1600s the basic sweat gland duct was
described, the existence of a sweat gland was not accepted until
the 1800s (96). Furthermore, the importance of sweating for
thermoregulation was not fully recognized until the 20th century. Especially noteworthy is Kuno’s monograph published in
1934 as The Physiology of Human Perspiration, and later
updated as “Human Perspiration” (65), which at that time
Address for reprint requests and other correspondence: M. Shibasaki, Kita-Uoya
Nishi-Machi, Nara 630-8506, Japan (e-mail: [email protected]).
1692
provided the most comprehensive review of sweating. Subsequently, many researchers have studied the physiology of
sweating toward a greater understanding of the mechanisms
and controllers of sweating. The objective of this review is to
outline these mechanisms and controllers of sweating, specifically during exercise and heat stress.
CONTROL OF THE ECCRINE SWEAT GLAND
Human sweat glands are generally divided into two types,
the apocrine and the eccrine gland. The eccrine gland is the
primary gland responsible for thermoregulatory sweating in
humans (110) and thus will be the focus of this review. For a
review of the apocrine gland the reader is referred to other
articles (28, 103). Eccrine sweat glands are distributed over
nearly the entire body surface. Sweat glands become identifiable in the palm and sole of the feet in the 16th fetal wk, and
in the 22nd wk or later sweat glands are identifiable on the rest
of the body (65). The number of sweat glands in humans varies
greatly, ranging from 1.6 to 4.0 million, with the density of
eccrine sweat glands associated with thermoregulation (i.e.,
precluding glands on the palms of the hands and soles of the
feet) being the greatest on the forehead, followed by the upper
limbs, and finally the trunk and lower limbs (60, 65, 109). The
structure of the eccrine sweat gland consists of a bulbous
secretory coil leading to a duct. The secretory coil is located in
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Shibasaki, Manabu, Thad E. Wilson, and Craig G. Crandall. Neural control and
mechanisms of eccrine sweating during heat stress and exercise. J Appl Physiol 100:
1692–1701, 2006; doi:10.1152/japplphysiol.01124.2005.—In humans, evaporative heat
loss from eccrine sweat glands is critical for thermoregulation during exercise
and/or exposure to hot environmental conditions, particularly when environmental
temperature is greater than skin temperature. Since the time of the ancient Greeks,
the significance of sweating has been recognized, whereas our understanding of the
mechanisms and controllers of sweating has largely developed during the past
century. This review initially focuses on the basic mechanisms of eccrine sweat
secretion during heat stress and/or exercise along with a review of the primary
controllers of thermoregulatory sweating (i.e., internal and skin temperatures). This
is followed by a review of key nonthermal factors associated with prolonged heat
stress and exercise that have been proposed to modulate the sweating response.
Finally, mechanisms pertaining to the effects of heat acclimation and microgravity
exposure are presented.
Invited Review
MECHANISMS FOR THE CONTROL OF SWEATING IN HUMANS
J Appl Physiol • VOL
channels, which initiates the release of an isotonic precursor
fluid from the secretory cells (110). This precursor fluid is
much like plasma but is devoid of proteins. In a noteworthy
series of in vitro studies, Sato (108) collected sweat samples
from an isolated secretory coil and from the sweat duct and
found that the solution from the duct was hypotonic relative to
the secretory coil. These and a number of earlier observations
led to the conclusion that, as the fluid travels up the duct
toward the surface of the skin, sodium and chloride are reabsorbed, resulting in sweat on the skin’s surface being hypotonic
relative to plasma. However, when the rate of sweat production
is elevated, as occurs during exercise or heat stress, ion
reabsorption mechanisms can be overwhelmed due to the large
quantity of sweat secreted into the duct, resulting in higher ion
losses. Thus the sodium content in sweat on the skin’s surface
is greatly influenced by sweat rate (14, 90, 109, 117, 118).
THERMAL CONTROL OF SWEATING
In the late 19th and early 20th centuries, the existence of a
thermoregulatory center within the hypothalamic region of the
brain was identified. Studies demonstrated that elevated brain
temperature engaged heat loss mechanisms in animals (8, 53,
80, 89). Reports from early investigators were somewhat
mixed with respect to the location of the primary controller of
sweating. Before the middle of the 20th century, it was thought
that skin temperature was more important in the control of
sweating relative to internal temperature (44, 154). For example, in 1923, Adolph (1) reported that, in nonexercising subjects, sweat rate was proportional to the effective environmental temperature above 90°F (⬃32°C) and suggested a close
correlation between sweating and superficial body temperature.
Kuno (65) later suggested that central thermoregulatory centers
were more important for temperature control, because sweating
responses were delayed despite increasing skin temperature
when exposed to elevated environmental temperatures. Kuno
proposed that, if skin temperature was the primary controller of
sweating, then sweating should have occurred immediately on
exposure to the elevated environmental conditions. Nevertheless, Kuno did not evaluate sweating as a function of internal
temperature in those studies.
In 1959, Benzinger (9, 10) proposed that, under steady-state
conditions the increased sweat rate caused by exercise and/or
variations in the environmental temperature were very closely
correlated to rises in tympanic temperature and that this relationship was stronger than the relationship between skin temperature and sweating. His proposition was later supported by
Nielsen and Nielsen (85), although they observed that rapid
decreases in mean skin temperature reduced sweat rate when
internal temperature remained stable. Given findings that internal and mean skin temperatures can control sweating, researchers began to assess the relationship between sweating
and various combinations of internal and skin temperatures
(45, 75, 81, 104, 105, 132, 153). This resulted in the concept of
mean body temperature, which represents the sum of a fraction
of internal and skin temperatures (e.g., 0.9 䡠internal temperature ⫹ 0.1䡠 mean skin temperature) (34, 38), and it is now
frequently used when expressing sweating responses during
exercise and during exposure to elevated ambient air temperatures (87, 156, 157).
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the lower dermis, and the duct extends through the dermal
layer and opens directly onto the skin surface. The uncoiled
dimension of the secretory portion of the gland approximates
30 –50 ␮m in diameter and 2–5 mm in length. The size of the
adult secretory coil ranges from 1 to 8 ⫻ 10⫺3 mm3 (111).
There is a positive correlation between the size of an individual
sweat gland and the maximal sweat rate of that gland (111).
Given the challenges of identifying neural tracks in humans,
the exact neurological pathways responsible for sweating are
not entirely understood. Evidence from animal studies suggests
that efferent signals from the preoptic hypothalamus travel via
the tegmentum of the pons and the medullary raphe regions to
the intermediolateral cell column of the spinal cord. In the
spinal cord, neurons emerge from the ventral horn, pass
through the white ramus communicans, and then synapse in the
sympathetic ganglia. Postganglionic nonmyelinated C fibers
pass through the gray ramus communicans, combine with
peripheral nerves and travel to sweat glands (65, 72, 84, 110).
Sympathetic nerve terminals cluster mainly around the secretory coil of the sweat gland, but a few projections extend to the
sweat duct (22, 23, 56, 143).
Direct recordings of postganglionic skin sympathetic nerve
activity (SSNA) is possible in humans and much of the early
work in this area was performed by Wallin and colleagues (25,
43, 149). This technique permits the assessment of the neural
signal responsible for sweating, as well as cutaneous vascular
and perhaps pilomotor responses (11, 12, 25). Because of the
potential for the integrated skin sympathetic recording to contain neural signals innervating these differing efferent structures, caution must be taken when trying to link the skin neural
signal to a particular efferent event (e.g., sweating, cutaneous
vasoconstriction, etc.). Nevertheless, during heat stress, SSNA
is partially synchronized with galvanic skin response (an index
of sweating) and pulsatile sweat expulsion (11, 133), and
⬃80% of SSNA bursts have been reported to be synchronized
with pulsatile sweat expulsion (134). These observations suggest that a large fraction of the recorded skin sympathetic
neural signal in heat stressed subjects is sudomotor in nature.
Acetylcholine is the primary neurotransmitter released from
cholinergic sudomotor nerves and binds to muscarinic receptors on the eccrine sweat gland (94, 142), although sweating
can also occur via exogenous administration of ␣- or ␤-adrenergic agonists (90, 94, 99, 107). Nevertheless, the observation
that local and systemic administration of atropine (a muscarinicreceptor antagonist) greatly attenuates or abolishes sweating
during a thermal challenge or during exogenous administration
of acetylcholine or its analogs (32, 55, 58, 71, 73) strongly
suggests that thermoregulatory sweating primarily occurs
through stimulation of muscarinic receptors. Released acetylcholine is rapidly hydrolyzed by acetylcholinesterase, and this
response may be one of a number of mechanisms by which
sweat rate is regulated (71, 120). Immunochemistry studies
have identified a number of possible peptide neuromodulators
(e.g., vasoactive intestinal polypeptide, calcitonin gene-related
peptide) in and around cholinergic sudomotor nerve terminals
and eccrine sweat glands (56, 116, 131, 135). Although some
evidence is present (64), the precise role of these peptides in
modulating sweating remain unclear.
When acetylcholine binds to muscarinic receptors on the
sweat gland, intracellular Ca2⫹ concentrations increase. This
results in an increase in the permeability of K⫹ and Cl⫺
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1694
MECHANISMS FOR THE CONTROL OF SWEATING IN HUMANS
Fig. 1. Effect of mean skin temperature on the relationship between sweat rate
and internal temperature. Initially, as internal temperature increases, sweating
does not occur. However, after a threshold is surpassed, the increase in sweat
rate parallels the rise in internal temperature, and this threshold can be shifted
by mean skin temperature. [Modified from Nadel et al. (81).]
J Appl Physiol • VOL
as 8 min of exercise or passive heat stress. In contrast, increases in sweat output per gland were more gradual and
continued to rise until the heating perturbation ceased.
Humans have the capability of producing a tremendous
amount of sweat during prolonged exercise in the heat. For
example, the highest reported sweat rate was ⬎3 l/h (7),
although average maximum sweat rates for humans are ⬃1.4
l/h (36). These high rates of sweating cannot be maintained for
prolonged periods of time, given findings that 4 – 6 h of heat
exposure decreases the rate of sweating (36, 141, 152, 155).
When sweating is reduced during prolonged heat stress or
exercise, the mechanism for this event, despite sustained elevations in internal temperature, is not entirely clear, although
both central and peripheral factors have been implicated. For
example, dehydration (i.e., hypohydration and elevated plasma
osmolality) inhibits sweating primarily through central mechanisms (see section below for an in-depth discussion of this
topic). However, dehydration does not explain decreases in
sweating during prolonged exposure to hyperthermic conditions when individuals are adequately hydrated. Under these
conditions, decreases in sweat rate may be due to the skin
being wet for prolonged periods of time, which can swell the
keratinized layer around the sweat duct, thereby mechanically
occluding the ducts and reducing sweat secretion (95).
EFFECT OF BODY FLUID REGULATION ON SWEATING
Prolonged exposure to hyperthermic conditions and/or prolonged exercise in the heat can induce water deficits due to
profuse sweating, resulting in dehydration. This water deficit
lowers both intracellular and extracellular volumes and results
in plasma hyperosmolality and hypovolemia, both of which
impair sweating. For example, Greenleaf and Castle (41) proposed that the excessive rise in internal temperature in dehydrated subjects was due to inadequate sweating. Expanding this
concept, Sawka et al. (115) observed that in progressively
dehydrated subjects sweat rate was dramatically reduced despite greater elevations in rectal temperature. Later, Montain et
al. (79) demonstrated that the threshold for the onset of sweating was elevated, whereas the slope of the relationship between
the elevation in sweat rate relative to the elevation in internal
temperature was attenuated, as a function of the level of
dehydration, both of which are strongly suggestive of impaired
sweating responsiveness.
Fortney et al. (31) conducted a study to identify the importance and independence of decreases in fluid volume (hypovolemia) from increases in plasma osmolality (hyperosmotic) on
sweat rate. Normovolemic subjects were exposed to heat
stresses under hyperosmotic and isoosmotic conditions while
sweat rate was assessed. During the ensuing exercise bout, the
internal temperature threshold for the onset of sweating was
significantly elevated relative to the response during exercise
under isoosmotic conditions. The slope of the relationship
between the elevation in sweating and the elevation in internal
temperature was not affected by increased plasma osmolality.
Takamata et al. (136, 138) extended these findings on assessing
sweat rate in heat-stressed subjects who received an infusion of
0.9 or 3% saline. They found that the threshold for sweating in
the hyperosmotic condition (i.e., 3% saline infusion) was
greatly shifted to a higher internal temperature relative to the
isoosmotic condition. This hyperosmolality-induced suppres-
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Although alluded to by others, Nadel and colleagues (82, 83)
were among the first to directly access the relationship between
the increase in sweat rate relative to dynamic increases in
internal temperature in humans. Later, this concept was confirmed in monkeys in which direct measures of brain temperature were obtained while sweating was assessed by Smiles et
al. (128). They concluded that sweating is primarily controlled
by central brain temperature and secondarily affected by mean
skin temperature. Given these findings, sweating responses are
now commonly characterized by the internal or mean body
temperature threshold for the onset of sweating, as well as the
slope of the relationship between the elevation in sweating and
the elevation in internal or mean body temperature (see Fig. 1),
as eloquently outlined in the reviews by Gisolfi and Wenger
(38). An increase in the internal or mean body temperature
threshold for the onset of sweating and/or an attenuation of the
elevation in sweating relative to the elevation in internal or
mean body temperature is recognized as impaired sweating
responsiveness.
Whereas mean skin temperature alters sweating via central
mechanisms, sweat rate is also influenced by local temperature
of the sweat gland via peripheral mechanisms (145). For
example, local heating accentuates sweat rate while local
cooling attenuates sweat rate (13, 69, 73, 86). Possible mechanisms by which local temperature alters sweating may be an
effect of temperature on neurotransmitter release [i.e., local
heating augments the release of acetylcholine for a given
neural stimulus, whereas local cooling attenuates neurotransmitter release (73, 81, 82)] or sensitization or desensitization of
the receptors on sweat glands by temperature (26, 86). It
remains unclear which of these mechanisms, or whether both,
are responsible for these observations.
Increases in sweating occur through the combination of
increasing the number of sweat glands that are activated and
increasing the amount of sweat released per gland. Randall et
al. (92, 93) and Kondo et al. (59) reported that the initial
increase in sweat rate during a heat stress is due to an increase
in the number of activated sweat glands, whereas further
elevations in sweating occur through increases in the production of sweat per gland. Kondo et al. extended those observations by reporting that recruitment of sweat glands was very
fast, with near maximal recruitment being achieved in as little
Invited Review
MECHANISMS FOR THE CONTROL OF SWEATING IN HUMANS
1695
and phenylephrine) to perturb baroreceptors without causing
cooling that accompanies LBNP. Despite pronounced changes
in blood pressure, neither SSNA nor sweat rate was significantly affected. However, it should be stressed that pharmacologically induced decreases in blood pressure will likely perturb baroreceptors differently relative to LBNP or head-up tilt.
Dodt et al. (27) addressed this question differently by exposing subjects to a mild heat stress, followed by 30° head-up
tilt. They observed significant reductions in forearm SSNA and
an index of sweat rate during tilt, and they concluded that
baroreceptor unloading could modulate SSNA and sweating.
Given what appeared to be a relatively minor heat stress in the
Dodt et al. study, differences in conclusions between their
study and others (21, 130, 148, 150) may be related to the level
of heat stress. For example, baroreceptors may be capable of
modulating sweating under mild to moderate heating conditions but not during more pronounced heat stress. To address
this question, Wilson et al. (151) measured peroneal SSNA and
sweat rate during multiple 30° head-up tilts, with tilting occurring every 10 min throughout the heat stress (Fig. 2). Regardless of the level of heating, they did not see a reduction in
sweat rate or SSNA during the same magnitude of tilt used by
Dodt et al. (27). Taken together, although findings remain
controversial, acute unloading of baroreceptors is unlikely to
modulate sweat rate.
MODIFICATION OF SWEATING DUE TO
BARORECEPTOR UNLOADING
Thermoregulation during exercise is very complicated, resulting in a number of proposed theories and concepts (38).
Compared with passive heat stress, generation of heat associated with muscular contraction during dynamic exercise rapidly elevates internal temperature, followed by appropriate
increases in sweat rate. It is interesting to note that factors
unrelated to the elevation in internal temperature that are
engaged during exercise may modulate the sweating response.
van Beaumont and Bullard (144, 146) were the first to report
this phenomenon on observing that sweating occurred immediately (within 1.5–2 s) with the onset of dynamic exercise and
Given that prolonged exposure to hyperthermic conditions
and/or exercise reduces blood volume if fluid intake is not
adequate, coupled with baroreceptors being sensitive to
changes in blood volume, it seems reasonable to hypothesize
that sweating associated with these conditions could be modulated by baroreceptor unloading. However, the effects of
baroreceptor unloading on attenuating the elevation in sweat
rate are controversial. Johnson and Park (51) assessed the
internal temperature threshold for the onset of sweating during
exercise and found that this threshold was unaltered regardless
of whether the individual exercised in the upright position (i.e.,
baroreceptor unloading) or supine position. In contrast, Mack
et al. (74) observed an increase in the internal temperature
threshold for the onset of sweating (i.e., a delayed sweating
response) during exercise in combination with lower body
negative pressure (LBNP), which simulates the upright position and unloads baroreceptors.
The effect of baroreceptor unloading on sweat rate was
further addressed by applying LBNP in passively (i.e., nonexercise) heat-stressed subjects (21, 130, 148). These studies
suggested that sweat rate was not affected by baroreceptor
unloading. A possible explanation for differences in findings
between LBNP studies (21, 74, 130, 148) was proposed by
Vissing et al. (148). They suggested that reduced electrodermal
response (index of sweating) and SSNA during LBNP results
from skin cooling that frequently occurs with application of the
negative pressure, not via baroreceptor unloading. To address
this question, Wilson et al. (150) assessed sweat rate and
peroneal SSNA in heat-stressed subjects during bolus and
steady-state infusions of pharmacological agents (nitroprusside
J Appl Physiol • VOL
MODIFICATION OF SWEATING RESPONSES DUE TO
EXERCISE-RELATED FACTORS
Fig. 2. Relationship between forearm sweat rate and mean body temperature
during consecutive 30° head-up tilts throughout a heat stress. Tilt 1 was
performed during normothermia (mean body temperature ⬃36.9°C), whereas
tilts 2– 6 were performed during heat stress; each tilt was separated by 10 min.
Values are means ⫾ SE. [Modified from Wilson et al. (151).]
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sion of the sweating occurred regardless of heat acclimation
status (47). In a follow-up study, Takamata et al. (136) found
that when hyperosmotic subjects drink deionized water (38°C),
sweat rate immediately increases without changes in plasma
osmolality, although drinking deionized water in isoosmotic
subjects did not alter sweat rate. These findings demonstrate
that increased plasma osmolality, independent of plasma volume, impairs sweating responses and that an oral-pharyngeal
reflex can modulate the sweating response in hyperosmotic
individuals (136).
Fortney et al. (30) addressed the opposite question relative to
that presented above, in that they investigated whether changes
in blood volume, while keeping plasma osmolality constant,
modulates the sweating response. They found that isoosmotic
hypovolemia reduced the slope of the relationship between the
change in sweating relative to the change in internal temperature, without altering the internal temperature threshold for the
onset of sweating (30). Such a finding suggests that, once
sweating has begun for the same elevation in internal temperature, there was less of an elevation in sweating. Conversely,
isoosmotic hypervolemia does not change the internal temperature threshold for sweating or the aforementioned slope (30,
66), unless plasma and blood volume expansion occurs via
erythrocyte infusion (113). These observations suggest that
sweating can be inhibited by isoosmotic hypovolemia, whereas
hypervolemia in the absence of erythrocyte infusion does not
alter sweating responses.
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MECHANISMS FOR THE CONTROL OF SWEATING IN HUMANS
increased sweat rate; however, the increase in sweat rate was
significantly greater when central command was augmented
after partial neuromuscular blockade (Fig. 3B). This, and a
related study assessing SSNA to isometric exercise during
partial neuromuscular blockade (147), provide strong evidence
that central command is capable of modulating sweating during
exercise.
Alam and Smirk (3, 4) showed that blood pressure increases
during dynamic and static exercise and remains elevated if
blood flow to that limb was occluded just before the cessation
of exercise. On release of the occlusion, blood pressure returned to preexercise levels. Their observations led to numerous and ongoing studies investigating the role of muscle
metaboreceptors in modulating blood pressure during exercise.
A number of studies have been performed to investigate the
possible role of metaboreceptors in modulating sweating responses during exercise (20, 61, 121). In general, the cited
studies were performed by monitoring sweat rate during isometric exercise and subsequent postexercise ischemia, the
latter of which isolates muscle metaboreceptor stimulation. In
those studies, sweat rate increased during isometric exercise,
remained elevated during postexercise ischemia, and then returned toward preexercise levels after release of ischemia (Fig.
3A). This pattern of response provides evidence that metaboreceptors are capable of modulating sweat rate during exercise.
However, during postexercise ischemia, blood pressure is also
elevated and may therefore contribute to the elevation in
sweating via loading of baroreceptors. To test this hypothesis,
Shibasaki et al. (121) performed an experiment in which blood
pressure during the postexercise ischemia period was restored
to preexercise levels via intravenous administration of sodium
nitroprusside (Fig. 3C). Under these conditions, muscle
metaboreceptors remained stimulated but blood pressure returned to preexercise levels. Despite normalized blood pressure, sweat rate remained elevated throughout the ischemic
period (121). Thus the elevation in sweat rate during postex-
Fig. 3. Hemodynamic and sweating responses
during isometric handgrip exercise followed by
postexercise ischemia under control conditions
(A), during partial neuromuscular blockade (B;
notice the reduction in force production), and
when blood pressure during post-exercise ischemia was returned to preexercise levels via systemic nitroprusside infusion (C). Isometric
handgrip exercise did not significantly change
skin or esophageal temperatures. Classical hemodynamic responses associated with isometric exercise and postexercise ischemia were
observed (A). Forearm sweat rate increased during isometric exercise in all 3 conditions, even
when force production was substantially reduced due to partial neuromuscular blockade
(B). During postexercise ischemia, sweat rate
remained elevated in the control condition (A)
and when blood pressure was returned to preexercise levels (C). In both conditions, sweat
rate returned to preexercise levels with the release of ischemia. IHG, isometric handgrip exercise; PEI, postexercise ischemia; ⌬Tes,
change in esophageal temperature; ⌬HR,
change in heart rate; ⌬SR, change in sweat rate;
Force, force produced during isometric exercise. [Modified from Shibasaki et al. (122).]
J Appl Physiol • VOL
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during isometric exercise in warm environmental conditions.
Importantly, this increase in sweating occurred before a measurable change in internal temperature. Later, Gisolfi and
Robinson (37) observed rapid changes in sweating during
intermittent exercise independent of changes in internal, muscle, or skin temperatures.
To address possible mechanisms by which exercise increases sweating independent of temperature, one needs to
understand the work of Johansson (50), who postulated that
two separate and distinct neural mechanisms control cardiovascular responses during exercise. One mechanism arises
from the central nervous system that irradiates impulses from
the motor cortex. Krogh and Lindhard (63) termed this central
mechanism as “cortical irradiation,” and later it was called
“central command” (39). The other mechanism, termed the
exercise pressor reflex, originates from the stimulation of
afferent nerve endings within the skeletal muscle and is engaged during muscle contraction (4). Later it was shown that
mechanosensitive afferent nerves and metabosensitive afferent
nerves were responsible for evoking the exercise pressor reflex
(77, 78). Because sweating during exercise can occur before a
change in thermal status, coupled with the aforementioned
responses associated with modulating cardiovascular responses
during exercise, researchers sought to identify whether similar
mechanisms could be responsible for modulating sweat rate
during exercise.
Partial neuromuscular blockade (e.g., using curare derivatives) has been used to augment central command during
exercise, resulting in greater increases in heart rate and blood
pressure at a given workload (49, 68, 77). Shibasaki et al. (124)
used this technique to test the hypothesis that central command
is capable of modulating the sweating response in heat-stressed
subjects. Heat-stressed subjects performed isometric exercise
under control conditions (without neuromuscular blockade)
and when central command was augmented via partial neuromuscular blockade. Under both conditions, isometric exercise
Invited Review
MECHANISMS FOR THE CONTROL OF SWEATING IN HUMANS
ercise ischemia occurred through activation of metaboreceptors
and was independent of the increase in blood pressure during
postexercise ischemia and presumably during isometric exercise. These findings strongly suggest that the muscle metaboreflex is capable of modulating sweat rate.
Another muscle afferent signal that could contribute to
sweating responses during exercise is that related to mechanical stimulation of the muscle (52, 62, 101, 123), which has
previously been suggested to contribute to the pressor response
during exercise (77, 78). These studies used protocols involving passive limb movement or passive cycling while assessing
sweating responses in heat-stressed subjects. In general, these
findings suggest that stimulation of muscle mechanoreceptors
is capable of modulating sweat rate, although responses appear
to be less than that observed during augmentation of central
command or muscle metaboreceptor stimulation.
Despite the aforementioned studies, not all studies support
the concept that sweating can be modulated by nonthermal
factors associated with exercise. For example, neither the
internal temperature threshold for the onset of sweating nor the
slope of the relationship between the elevation in sweating
relative to the elevation in internal temperature is different
when responses are compared between dynamic exercise and
passive heating states (51, 54, 59). Such findings are perplexing given that, relative to resting conditions, central command,
muscle metaboreceptor, and muscle mechanoreceptors are
stimulated during dynamic exercise. Furthermore, the internal
temperature threshold for the onset of sweating is not altered
by exercise intensity, whereas the slope of the relation between
elevations in sweating and internal temperature is not changed
in the majority of studies (15, 60, 104, 105, 140); however, one
study found an elevation of this slope with exercise intensity
(79). A key difference between those studies showing an effect
of central command and metabo- and mechanoreceptors stimulation in modulating sweating with those that do not may be
the magnitude of the heat stress before the perturbation. For
example, in those studies in which sweating is already engaged, or is very close to the threshold to be engaged, stimuJ Appl Physiol • VOL
lating the aforementioned nonthermal factors associated with
exercise more consistently increases sweat rate. This is in
contrast to those studies in which exercise began with the
subject in a normothermic state and thus nonsweating condition, where sweating is reported to be less affected by nonthermal factors associated with exercise. Another potential explanation for differences in these findings may be related to
whether the workload was static or dynamic. Clear influences
of nonthermal factors in modulating sweating are observed
when static (i.e., isometric) exercise is used as the perturbation,
whereas these influences are less pronounced when dynamic
exercise is used. Undoubtedly, further studies are needed to
clarify the effects of nonthermal factors during exercise, and
possible interaction between these factors, on sweat responses.
MODIFICATION OF SWEATING RESPONSES DUE TO HEAT
ACCLIMATION AND MICROGRAVITY EXPOSURE
Physiological systems have the ability to adapt to differing
environmental conditions. Inclusive in its adaptability are systems responsible for thermoregulation, including sweating.
Examples of the capacity for sweating to adapt are demonstrated in the effects of heat acclimation as well as simulated or
actual microgravity exposure on sweating responses, which
increase and decrease, respectively, sweat rate for a given
internal temperature.
With repeated exposure to hyperthermic environmental conditions, sweat rate is elevated for a given internal temperature
(2, 17, 46, 70, 83, 102, 126, 127), coupled with a decreased
sodium concentration in the sweat (5, 24, 57, 129). Thus,
although heat acclimated individuals sweat more, there is less
sodium in that sweat. Detailed examination of the effects of
heat acclimation on sweating responses show that this exposure
decreases the internal temperature threshold for the onset of
sweating (Fig. 4), resulting in a greater cooling capacity
Fig. 5. Schematic illustrating possible nonthermal modifiers of sweating
including factors associated with exercise (i.e., central command and muscle
mechano- and metaboreceptors), baroreflexes (carotid, aortic, and cardiopulmonary baroreceptors), and osmoreceptors. Arrows indicate identified as well
as hypothesized neural connections between osmoregulatory, thermoregulatory, and cardiovascular centers. [Modified from Shibasaki et al. (122)].
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Fig. 4. Impact of heat acclimation or exercise training, as well as microgravity
exposure, on the relationship between internal temperature and sweat rate.
Heat acclimation or exercise training shifts this relationship to lower internal
or mean body temperature, whereas microgravity exposure or deconditioning
shifts the threshold for the onset of sweating to higher internal or mean body
temperature. This figure only depicts changes in the internal temperature
threshold for the onset of sweating by these perturbations. Some of these
perturbations have been shown to also alter the slope of the relationship
between the elevation in sweat rate relative to the elevation in internal
temperature.
1697
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CONCLUSION
Sweating from eccrine glands is essential for thermoregulation during heat stress and/or exercise. On the surface, it may
J Appl Physiol • VOL
appear that control of sweating is simplistic in that people
sweat when they are heat stressed. However, like so many
physiological systems, this view is not comprehensive, and, as
covered in this review, there are a number of factors that alter
the magnitude and composition of sweat (Fig. 5). These factors
should be viewed as fine tuners of the sweating response to
form a balance between temperature regulation and nonthermal
stressors imposed by the condition (i.e., exercise, dehydration,
etc.). The objective of this review was to provide a brief and
comprehensive summary of the mechanisms and controllers of
sweating in humans. For a detailed review of the history of
sweating research (96, 97), mechanisms of sweat gland function (90, 91, 103, 107, 110), nonthermal modulation of sweating responses (112, 119, 122, 137), or sweating response to
various environmental stressors (35, 40, 100, 139), the reader
is referred to these informative articles.
ACKNOWLEDGMENTS
The authors acknowledge the many investigators who focus on this field of
study and whose work should be cited in this review but because of page
limitations are not included.
GRANTS
Support for the authors was provided by Grant-in-Aid for the Encouragement of Young Scientists from the Japanese Society for the Promotion of
Science Grants 14704020 and 17790162 (to M. Shibasaki); the American
Heart Association (to T. E. Wilson); National Heart, Lung, and Blood Institute
Grants HL-61388 and HL-67422 (to C. G. Crandall) and HL-10488 (to T. E.
Wilson); and National Institute of General Medical Sciences Grant GM-68865
(to C. G. Crandall)
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