J Appl Physiol 92: 1635–1641, 2002;
10.1152/japplphysiol.00981.2001.
Estrogen attenuates the cardiovascular and ventilatory
responses to central command in cats
SHAWN G. HAYES, NICOLAS B. MOYA DEL PINO, AND MARC P. KAUFMAN
Division of Cardiovascular Medicine, Departments of Internal Medicine
and Human Physiology, University of California, Davis, California 95616
Received 25 September 2001; accepted in final form 5 December 2001
exercise pressor reflex; heart rate; arterial blood pressure;
tendon stretch; muscle afferents
TWO NEURAL MECHANISMS, namely, central command and
the exercise pressor reflex, are widely believed to evoke
the cardiovascular and ventilatory responses to exercise (17, 36). Central command is defined as the parallel activation of neural circuits in the brain stem and
spinal cord that control motor, ventilatory, and cardiovascular function. Central command does not require
feedback from the periphery (10). The exercise pressor
reflex arises from the stimulation of group III and IV
muscle afferents. This reflex is believed to be evoked by
mechanical and metabolic factors in muscles while
they are contracting (4, 18, 24).
The cardiovascular responses to exercise have been
reported to be less in premenopausal women than in
postmenopausal women or men (11, 12). The difference
has been attributed to estrogen, a hormone that is well
known to decrease vascular resistance (28). In addi-
Address for reprint requests and other correspondence: S. G.
Hayes, Div. of Cardiovascular Medicine, TB 172, One Shields Ave.,
Davis, CA 95616 (E-mail: [email protected]).
http://www.jap.org
tion, estrogen administration to postmenopausal
women with mild hypertension has been reported to
attenuate the pressor response to exercise (27). These
studies, however, provided no direct evidence that estrogen exerted its effect on central command or the
exercise pressor reflex. Consequently, we were
prompted to investigate this issue in decerebrate cats.
Using this preparation, we were able to examine the
effect of estrogen on the cardiovascular and ventilatory
responses to central command and to the exercise pressor reflex, each of which was evoked separately.
METHODS
General. Adult male cats were anesthetized with a mixture
of 5% halothane and oxygen. Catheters were placed in the
right jugular vein and common carotid artery for delivery of
drugs and measurement of arterial blood pressure, respectively. The carotid artery catheter was connected to a pressure transducer (model P23 XL, Statham) to measure arterial pressure. Heart rate was calculated beat-to-beat from the
arterial pressure pulse by a Gould Biotach amplifier. The
trachea was cannulated, and the lungs were ventilated mechanically (Harvard Apparatus) for the remainder of the
surgical preparation. The cat was placed in a Kopf stereotaxic and spinal unit, after which the brain stem was
transected 0.5 mm anterior to the superior colliculus. The
plane of section was perpendicular to the brain stem. All
neural tissue rostral to the section was removed. Hemostasis
was achieved, and the cranial vault was filled with agar
(37°C). The cat was then removed from the ventilator and
breathed room air spontaneously. In preparations that were
not paralyzed, airflow was measured with a pneumotachograph (Fleisch) that was attached in series with the tracheal
cannula. Airflow was integrated (Gould) breath-by-breath to
yield tidal volume, which subsequently was used to calculate
minute volume of ventilation. Alternatively, in paralyzed
preparations that were mechanically ventilated, phrenic
nerve activity was recorded from a central cut end of a C5
rootlet. This activity was integrated according to the method
described by Eldridge (9) to yield an index of tidal volume.
Integrated phrenic nerve activity was expressed in arbitrary
units (AU). In addition, the tibial nerve was cut in these
paralyzed preparations, and its central end was placed on a
bipolar recording electrode. Electrical activity from presumed motoneurons in the tibial nerve was amplified (model
P511, Grass) and recorded (model ES 1000, Gould). Likewise,
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.
8750-7587/02 $5.00 Copyright © 2002 the American Physiological Society
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Hayes, Shawn G., Nicolas B. Moya Del Pino, and
Marc P. Kaufman. Estrogen attenuates the cardiovascular
and ventilatory responses to central command in cats. J Appl
Physiol 92: 1635–1641, 2002; 10.1152/japplphysiol.00981.
2001.—Static exercise is well known to increase heart rate,
arterial blood pressure, and ventilation. These increases appear to be less in women than in men, a difference that has
been attributed to an effect of estrogen on neuronal function.
In decerebrate male cats, we examined the effect of estrogen
(17␤-estradiol; 0.001, 0.01, 0.1, and 1.0 ␮g/kg iv) on the
cardiovascular and ventilatory responses to central command and the exercise pressor reflex, the two neural mechanisms responsible for evoking the autonomic and ventilatory responses to exercise. We found that 17␤-estradiol, in
each of the three doses tested, attenuated the pressor, cardioaccelerator, and phrenic nerve responses to electrical
stimulation of the mesencephalic locomotor region (i.e., central command). In contrast, none of the doses of 17␤-estradiol
had any effect on the pressor, cardioaccelerator, and ventilatory responses to static contraction or stretch of the triceps
surae muscles. We conclude that, in decerebrate male cats,
estrogen injected intravenously attenuates cardiovascular
and ventilatory responses to central command but has no
effect on responses to the exercise pressor reflex.
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ESTROGEN AND EXERCISE
J Appl Physiol • VOL
minute volume (i.e., for 60 s) immediately before (i.e., baseline) and during a maneuver (“peak”). Statistical analyses
were conducted using SigmaStat 2.0, and tests were a oneand a two-way repeated-measures ANOVA. Dunnett’s and
Tukey’s post hoc tests were used for the one- and two-way
repeated-measured ANOVAs, respectively, The criterion for
statistical significance was P ⬍ 0.05.
RESULTS
Reflex experiments. In decerebrate unanesthetized
cats, intravenous injection of 17␤-estradiol at three
doses [0.01 ␮g/kg (n ⫽ 4), 0.1 ␮g/kg (n ⫽ 5), and 1.0
␮g/kg (n ⫽ 5)] had no measurable effects on the pressor, cardioaccelerator, or ventilatory responses to static
contraction of the triceps surae muscles or stretch of
the calcaneal tendon (Figs. 1 and 2, Table 1). Like
others (38), we found that tendon stretch had weak and
variable effects on ventilation. This was found to be the
case for each contraction and tendon stretch that was
performed at 15-min intervals during the 2-h period
after injection. Estradiol at 0.01 ␮g/kg increased baseline arterial blood pressure. For example, during tendon stretch (n ⫽ 4), baseline MAP significantly increased from 85 ⫾ 11 mmHg before estradiol to 119 ⫾
10 mmHg 60 min after estradiol (P ⬍ 0.05; Fig. 2).
Baseline MAP never returned to preestradiol levels 4 h
after estradiol. At doses of 0.1 ␮g/kg (n ⫽ 5) and 1.0
␮g/kg (n ⫽ 5), however, baseline MAP remained unchanged. Similarly, during tendon stretch (n ⫽ 4),
baseline heart rate in cats given estradiol at 0.01 ␮g/kg
increased from 148 ⫾ 13 to 169 ⫾ 13 beats/min (P ⬍
0.05; Fig. 2). Again, estradiol at 0.1 ␮g/kg (n ⫽ 5) and
1.0 ␮g/kg (n ⫽ 5) did not change baseline heart rate
(Figs. 1 and 2). Estradiol had no significant effects on
baseline ventilation at any dose tested.
Central command. In decerebrate paralyzed cats,
intravenous injection of 17␤-estradiol at 0.01, 0.1, and
1.0 ␮g/kg (n ⫽ 6 for each dose) significantly decreased
the pressor, cardioaccelerator, and phrenic neural responses to MLR stimulation (Figs. 3–5). MLR stimulation evoked rhythmic electrical activity from the tibial nerve in 18 cats and tonic activity in 3 cats. The
pressor response to MLR stimulation was significantly
attenuated 60 min after estradiol at each of the three
effective doses tested (n ⫽ 6 for each dose). At 120 min
after injection, the pressor response to MLR stimulation returned to preestradiol levels (Figs. 3 and 4).
Baseline MAP was not affected by estradiol. The cardioaccelerator response to MLR stimulation was significantly attenuated 60 min after estradiol at each of the
three doses tested (P ⬍ 0.05, n ⫽ 6 for all doses). At 120
min, however, the responses to MLR stimulation returned to preestradiol levels (Figs. 3 and 4). Baseline
heart rate was not affected by estradiol. The phrenic
nerve response to MLR stimulation was significantly
attenuated 60 min after estradiol at each of the three
doses tested (P ⬍ 0.05, n ⫽ 6 for all doses). At 120 min,
however, the phrenic nerve response to MLR stimulation had returned to preestradiol levels (Figs. 3 and 4).
Baseline phrenic nerve activity was not affected by
estradiol.
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arterial pressure, heart rate, tidal volume, integrated
phrenic nerve activity, and tension development by the triceps surae muscles were recorded (model ES 1000, Gould).
Protocols. Central command was evoked by electrically
stimulating (30–50 Hz, 0.5 ms, 40–100 ␮A) the mesencephalic locomotor region (MLR) for 60 s with an FHC monopolar stainless steel electrode. The stereotaxic coordinates of
the MLR were P2, L4, and H1 (31). When successful, MLR
stimulation evoked locomotion in the unparalyzed cat. After
finding a site in the MLR that evoked locomotion, we paralyzed the cat by injecting pipecuronium bromide (0.1 mg/kg
iv). We then examined the effect of 17␤-estradiol, injected
intravenously, on the pressor, cardioaccelerator, and phrenic
nerve responses to MLR stimulation. The maximum current
used in our experiments (i.e., 100 ␮A) has been shown to
spread over a radius of 0.5 mm (2). The following doses of
17␤-estradiol were used: 0.001, 0.01, 0.1, and 1 ␮g/kg. The
17␤-estradiol was water soluble and was diluted with saline.
Only one dose of 17␤-estradiol was given to a cat. After
injecting that dose, we stimulated the MLR at 15-min intervals until 120 min had elapsed. Before each MLR stimulation, we ensured that the cat was paralyzed. Pipecuronium
bromide is a long-lasting paralytic agent, and thus it was
usually not necessary to give more than one additional dose
60 min after the initial dose.
In three decerebrate cats, we examined the cardiovascular
and ventilatory responses to MLR stimulation in the presence of ICI-182780 (100 ␮g/kg iv), a receptor antagonist to
17␤-estradiol (35). We injected this antagonist 5 min before
injecting the highest dose of 17␤-estradiol (i.e., 1.0 ␮g/kg iv).
We did not examine the antagonizing effect of ICI-182780 on
the two lower doses of 17␤-estradiol (i.e., 0.01 and 0.1 ␮g/kg).
The exercise pressor reflex was evoked by electrically stimulating (40 Hz, 0.1 ms, ⬍3 times motor threshold) the cut
peripheral ends of the left L7 and S1 ventral roots. To accomplish this, we performed a laminectomy, exposing the L2 –S4
spinal cord. Using the skin on the back, we formed a pool that
was filled with warm (37°C) mineral oil. We sectioned all
visible nerves supplying the left hindlimb, except the tibial
nerve, which supplies the triceps surae muscles. The calcaneal bone was severed, and its tendon was attached to a force
transducer (model FT 10, Grass), which in turn was attached
to a rack-and-pinion. The knee was clamped in place. The
tendon was stretched so that baseline tension was 1.0 kg. We
examined the effect of 17␤-estradiol, injected intravenously,
on the pressor, cardioaccelerator, and ventilatory responses
to static contraction of the triceps surae muscles. The contraction period was 60 s. The following doses of 17␤-estradiol
were used: 0.01, 0.1, and 1.0 ␮g/kg. After injecting a dose, we
contracted the triceps surae muscles at 15-min intervals
until 120 min had elapsed.
A muscle mechanoreceptor reflex (33) was evoked by
stretching the calcaneal (Achilles) tendon by manually turning the rack-and-pinion, which was placed in series with the
force transducer. Baseline tension was set at 1.0 kg. Tendon
stretch and muscle contraction were performed on the same
cats, whereas, with one exception, MLR stimulation was
performed on a separate group of cats. Hence, the following
doses of 17␤-estradiol were used: 0.01, 0.1, and 1.0 ␮g/kg.
Only one dose of 17␤-estradiol was given to each cat. After
injecting that dose, we stretched the calcaneal tendon at
15-min intervals until 120 min had elapsed.
Data analysis. Values for mean arterial blood pressure
(MAP), heart rate, and minute ventilation are means ⫾ SE.
Baseline MAP and heart rate were recorded immediately
before a maneuver; peak values represent the highest level
reached during a maneuver. Ventilation was calculated as a
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ESTROGEN AND EXERCISE
Fig. 1. Lack of effect of 17␤-estradiol, administered intravenously in 3 doses, on pressor,
cardioaccelerator, and ventilatory responses
to static contraction of triceps surae muscles.
Peak responses are depicted by open bars,
and corresponding baseline values for each
response, with 1 exception, are shown inside
the open bars. All responses are significantly
greater (P ⬍ 0.05) than their corresponding
baseline values. Before, responses before estradiol administration; 60, responses 60 min
after estradiol administration; MAP, mean
arterial pressure; HR, heart rate [beats/min
(bpm)]; V̇E, minute volume of ventilation
measured during expiration.
to MLR stimulation 60 min after injection. In addition,
this subsequent dose of 17␤-estradiol decreased the
cardioaccelerator (from 41 ⫾ 17 to 27 ⫾ 12 beats/min)
and the phrenic neural (from 253 ⫾ 36 to 203 ⫾ 43 AU)
responses to MLR stimulation, but neither effect was
significant (P ⬍ 0.05) presumably because of the small
sample size. The data from these three cats are not
included in Fig. 3.
Estrogen receptor antagonist. In three cats, the cardiovascular and phrenic neural responses to MLR
Fig. 2. Lack of effect of 17␤-estradiol, administered intravenously in 3 doses, on pressor,
cardioaccelerator, and ventilatory responses
to stretch of the calcaneal tendon. Peak responses are depicted by open bars, and corresponding baseline values for each response,
with 1 exception, are shown inside open bars.
All pressor and cardioaccelerator responses
are significantly greater (P ⬍ 0.05) than their
corresponding baseline values. None of the
ventilatory responses are significantly different (P ⬎ 0.05) from their corresponding baseline values. See Fig. 1 legend for abbreviations.
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Smaller doses of 17␤-estradiol. In three decerebrate
cats, we were not able to attenuate the pressor cardioaccelerator and phrenic neural responses to MLR stimulation 60 min after injection of 17␤-estradiol at 0.001
␮g/kg iv. Moreover, this lowest dose of 17␤-estradiol
had no effect on baseline arterial blood pressure, heart
rate, and phrenic nerve activity. In these three cats,
subsequent administration of a logarithmically higher
dose (0.01 ␮g/kg iv) significantly attenuated the pressor response (from 60 ⫾ 15 to 43 ⫾ 13 mmHg, P ⬍ 0.05)
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ESTROGEN AND EXERCISE
731 ⫾ 127 AU, respectively. The antagonist had no
effect on baseline values.
Table 1. Peak tension developed by contracting and
stretching triceps surae muscles
n
0.01 ␮g/kg
CX
Before
60 min
TS
Before
60 min
0.1 ␮g/kg
CX
Before
60 min
TS
Before
60 min
1.0 ␮g/kg
CX
Before
60 min
TS
Before
60 min
4
Tension, kg
DISCUSSION
4.6 ⫾ 0.7
4.3 ⫾ 0.7
3.9 ⫾ 0.4
4.0 ⫾ 0.4
5
3.4 ⫾ 0.3
3.3 ⫾ 0.4
4.1 ⫾ 0.3
4.1 ⫾ 0.2
5
3.7 ⫾ 0.6
3.3 ⫾ 0.5
4.1 ⫾ 0.4
4.1 ⫾ 0.4
Values are means ⫾ SE; n, number of data points comprising each
mean. CX, static contraction; TS, tendon stretch; Before, tension
developed before administration of 17␤-estradiol; 60 min, tension
developed 60 min after administration of 17␤-estradiol.
stimulation were not attenuated by the highest dose of
17␤-estradiol tested (1 ␮g/kg iv) when ICI-182780 (100
␮g/kg iv) was injected 5 min before administration of
this sex steroid. Specifically, the pressor, cardioaccelerator, and phrenic neural responses to MLR stimulation before the antagonist averaged 74 ⫾ 19 mmHg,
34 ⫾ 13 beats/min, and 624 ⫾ 145 AU, respectively.
Likewise, these responses 60 min after the antagonist
averaged 81 ⫾ 21 mmHg, 41 ⫾ 20 beats/min, and
We have shown that intravenous injection of 17␤estradiol (i.e., estrogen) attenuated the cardiovascular
and ventilatory responses to electrical stimulation of
the MLR but had no effect on the responses to static
contraction and to stretch of the triceps surae muscles.
The MLR is believed to be an anatomic locus for central
command (10). Stimulation of the MLR in a paralyzed
preparation activates central command in the absence
of the exercise pressor reflex. Likewise, contraction of
the triceps surae muscles, a maneuver induced by
electrical stimulation of motoneurons in the ventral
roots, activates the exercise pressor reflex in the absence of central command.
An important issue for our experiments concerns the
relationship between the amount of estrogen injected
and physiological levels of this hormone. In our experiments, we did not measure the concentration of 17␤estradiol in the blood. Nevertheless, some estimates
can be calculated. For example, if we assume that all
the 17␤-estradiol injected remained in the blood and
that the blood volume of a 3-kg cat is 240 ml, then our
dose of 0.01 ␮g/kg would have created a blood concentration that would have been about twice that measured at peak estrus (34). Clearly, the actual concentration of 17␤-estradiol in the blood would have been
less than this amount, because some would have diffused into the cells and some would have been metabolized. Previous studies reported that intravenously
administered sex steroids were almost completely
eliminated from the blood 60 min after injection (14,
16). In any event, the attenuation of these responses by
Fig. 3. 17␤-Estradiol, administered intravenously in 3 doses, attenuated pressor, cardioaccelerator, and ventilatory responses to
mesencephalic locomotor region (MLR) stimulation. Peak responses are depicted by open
bars, and corresponding baseline values are
shown inside or outside open bars. All responses are significantly greater (P ⬍ 0.05)
than their corresponding baseline values.
* Response to MLR stimulation 60 min after
estradiol injection (60) was significantly less
(P ⬍ 0.05) than response to MLR stimulation
before (before) or 120 min after (120) injection
of estradiol. PNA, phrenic nerve activity in
arbitrary units (AU); see Fig. 1 legend for
other abbreviations.
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17␤-Estradiol
ESTROGEN AND EXERCISE
1639
Fig. 4. Effect of 17␤-estradiol (0.01 ␮g/kg iv) on pressor, cardioaccelerator, and integrated phrenic nerve responses to stimulation of the
MLR (40 Hz, 0.5 ms, 45 ␮A) in a paralyzed cat. A: responses to MLR
stimulation before injection of 17␤-estradiol. B: responses to MLR
stimulation 60 min after injection of 17␤-estradiol. C: responses to
MLR stimulation 120 min after injection of 17␤-estradiol. Period of
stimulation is represented by horizontal bar, which also depicts a
60-s time period. Activity recorded from the tibial nerve was rhythmic but cannot be seen at the chart recorder speed shown. ENG,
electroneurogram recorded from cut central end of the tibial nerve;
BP, arterial blood pressure.
17␤-estradiol was unlikely to be a nonspecific steroid
effect, because it was prevented by the estrogen receptor antagonist ICI-182780.
We do not know the mechanisms by which estrogen
administration in our experiments attenuated the responses to MLR stimulation but had no effect on responses to static contraction or to tendon stretch. One
possible cause might have been that the hormone increased the sensitivity of the baroreceptor reflex (30). If
this were the case, however, sensitization of the
baroreflex by estrogen should have been observed for
the reflexes arising from the triceps surae muscles as
well as for the responses to MLR stimulation. Moreover, the pressor responses arising from static contraction and tendon stretch, although not as large as those
arising from MLR stimulation, were more than sufficient to reveal baroreflex sensitization by estrogen. For
example, previous studies have shown that 17␤-estradiol administration sensitized the baroreflex when it
J Appl Physiol • VOL
Fig. 5. Time course of attenuating effects of 17␤-estradiol at 0.01 ␮g
on cardiovascular and phrenic neural (PNA) responses to MLR
stimulation in 6 cats. C, control responses evoked before administration of 17␤-estradiol. * Significantly different from control response
(P ⬍ 0.05).
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was evoked by increases in arterial pressure ranging
from 20 to 40 mmHg (13, 29, 30).
A second cause of the estrogen-induced attenuation
of the responses to MLR stimulation but not those to
contraction or tendon stretch might involve the distribution of estrogen receptors in the brain and spinal
cord. If this distribution is the cause, it is not readily
apparent from a review of the literature. For example,
there appears to be a paucity of estrogen receptors in
the cunneiform nucleus, the midbrain site that contains the MLR (20, 26). In contrast, estrogen receptors
are abundant in the superficial and deep laminae of the
dorsal horn (1, 32), sites that receive synaptic input
from group III and IV muscle afferents (5, 25).
Estrogen is well known to be antinociceptive in humans and rats (6, 22), a finding that raises an interesting issue for any conclusions drawn from our data.
Specifically, the possibility exists that static contraction of the triceps surae muscles stimulated nociceptive
as well as nonnociceptive afferents (17, 18). Consequently, one might expect that estrogen injection in our
experiments would attenuate the reflex cardiovascular
and ventilatory responses to static (i.e., tetanic) con-
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J Appl Physiol • VOL
sex hormone on the baroreceptor reflex. These investigators found that estrogen injected intravenously potentiated the baroreceptor reflex after a latency of
30–90 min, a period of time that is reasonably similar
to the latency reported by us. Estrogen appears to have
an effect on the central neural circuitry controlling
cardiovascular function, the cellular mechanism of
which remains to be determined. Nevertheless, the 30to 90-min latency found in each of these studies suggests that the effect may have been genomic (21).
A body of evidence is developing that suggests that
estrogen acting on the central nervous system has
important effects on the control of the circulation. Specifically, estrogen appears to decrease sympathetic
tone and to increase parasympathetic tone. For example, microinjection of 17␤-estradiol into the rostral
ventrolateral medulla of anesthetized rats decreased
renal sympathetic discharge and increased cervical
vagal discharge (29). In addition, oral administration
of a single dose of estrogen to men attenuated the
pressor response to mental stress (7). Furthermore,
centrally acting estrogen is believed, at least in part, to
be the cause of the finding that parasympathetic tone
to the heart is higher in women than in men (8). Thus,
in our studies, estrogen might have acted on some
central neural circuit, such as that described in the
rostral ventrolateral medulla (29), to reduce the cardiovascular responses to MLR stimulation. Although
the specific nature and location of this circuit remain to
be described, we note with interest that the MLR has
been shown to project to the rostral ventrolateral medulla (3), a site that has a relatively high density of
estrogen receptors (32).
In conclusion, we could find no evidence in decerebrate male cats that estrogen attenuated the pressor
reflex response to static contraction or to tendon
stretch. In contrast, we were able to show that estrogen
across a range of doses tested attenuated the cardiovascular and ventilatory responses to MLR stimulation. Our findings raise the possibility that gender
differences in the autonomic and ventilatory responses
to exercise in humans are caused by estrogen-induced
attenuation of central command.
We thank E. English for typing the manuscript.
This work was supported by National Heart, Lung, and Blood
Institute Grants HL-30710 and HL-64125.
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Our finding that administration of 17␤-estradiol had
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might appear at first glance to conflict with the finding
by Ettinger et al. (11), who reported that premenopausal women displayed smaller pressor and muscle
sympathetic nerve activity responses to static handgrip than did men of similar age. Ettinger et al. attributed this difference to an attenuated muscle metaboreflex in women. There are three important differences
between our experiments and those of Ettinger et al.
First, we used a 1-min contraction period, whereas
Ettinger et al. used a 2-min period. This difference
might have produced more metabolites in the working
muscles in the experiments of Ettinger et al. than in
our experiment. Second, and possibly most important,
we used cats, whereas Ettinger et al. used humans.
The importance of this difference, in addition to the
obvious difference pertaining to species, is that in cats
the metabolic by-products of triceps surae contraction
have been measured by microdialysis (23), whereas in
humans the by-products for static handgrip have been
measured by NMR (11). The time course and the specific metabolites measured by the two techniques were
different. Consequently, any comparison between the
two studies (11, 23) would be difficult. A difference
between humans and cats in these metabolites might
be critical if estrogen exerts its effects on the responsiveness of metaboreceptors to contraction. Third, we
injected estrogen as a bolus, whereas Ettinger et al.
(11, 12) allowed this hormone to vary naturally. We
suspect that the effects of estrogen on neural function
would be maximized by our approach, and clearly this
effect would have contributed to our findings.
In contrast to humans, gender in dogs appears to
play no role in attenuating the cardiovascular responses to exercise (19). One explanation for this finding might be that the frequency of changes in plasma
levels of estrogens in dogs is only twice per year,
whereas in humans it is 12 times per year. Consequently, the effects of estrogen surges on neural function in dogs might have dissipated at the time of
testing.
We can offer no explanation as to why the attenuating effect of estrogen usually occurred 45–60 min after
intravenous injection in our studies. Nevertheless,
some interesting parallels can be drawn between our
findings and those of He et al. (13) and Saleh and
Connell (30), both of whom examined the effect of this
ESTROGEN AND EXERCISE
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