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Division of Cardiovascular Medicine, Departments of Internal Medicine and Human Physiology, University of California, Davis, California 95616
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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In decerebrate unanesthetized cats, we determined whether either "central command," the exercise pressor reflex, or the muscle mechanoreceptor reflex reset the carotid baroreflex. Both carotid sinuses were vascularly isolated, and the carotid baroreceptors were stimulated with pulsatile pressure. Carotid baroreflex function curves were determined for aortic pressure, heart rate, and renal vascular conductance. Central command was evoked by electrical stimulation of the mesencephalic locomotor region (MLR) in cats that were paralyzed. The exercise pressor reflex was evoked by statically contracting the triceps surae muscles in cats that were not paralyzed. Likewise, the muscle mechanoreceptor reflex was evoked by stretching the calcaneal tendon in cats that were not paralyzed. We found that each of the three maneuvers shifted upward the linear relationship between carotid sinus pressure and aortic pressure and heart rate. Each of the maneuvers, however, had no effect on the slope of these baroreflex function curves. Our findings show that central command arising from the MLR as well as the exercise pressor reflex are capable of resetting the carotid baroreflex.
mesencephalic locomotor region; group III and IV afferents; neural control of circulation; cats
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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MODERATE AND SEVERE DYNAMIC EXERCISE increase arterial blood pressure (Pa), cardiac output, and sympathetic discharge to the vasculature of the viscera, skin, and skeletal muscles. The activation of two neural mechanisms, central command (30) and the exercise pressor reflex (13), are believed to cause these effects. The combination of both neural mechanisms along with metabolic vasodilation alters systemic vascular conductance to meet the increased metabolic requirements of exercising muscles.
Meanwhile, Pa is controlled moment to moment by the arterial baroreflex, a feedback mechansim that counteracts acute changes in arterial pressure by effecting cardiac output and systemic vascular conductance (27). The behavior of this reflex during exercise has attracted attention because the baroreflex control of the circulation and the autonomic responses to dynamic exercise represent two potentially conflicting control mechanisms. Specifically, activation of both central command and the exercise pressor reflex increase Pa, whereas the baroreflex would be expected to oppose this increase.
The baroreflex has been shown to function normally during exercise, but its operating point, defined as the pressure at the receptor around which the reflex is regulating Pa (26), appears to be shifted upward. For example, studies in rabbits (6) and humans (28) showed that partial restraint of the pressor response to exercise by slow infusion of nitroglycerine resulted in augmented sympathetic nerve and heart rate effects. Likewise, control of baroreceptor input with neck suction in humans yielded similar effects (24). This upward shift in the operating point has been termed baroreflex resetting (10), and there is substantial evidence that it occurs during exercise (3, 11, 20, 31, 32).
Both central command and input from the thin fiber afferents evoking the exercise pressor reflex have been proposed as the mechanisms causing baroreflex resetting. Strong evidence has emerged in support of the reflex mechanism as the cause of baroreflex resetting during exercise (12, 19, 21, 23). In contrast, evidence in support of central command resetting the baroreflex is less convincing.
We, therefore, sought to provide evidence that central command resets the carotid baroreflex. Central command was evoked in decerebrated paralyzed cats by electrically stimulating the mesencephalic locomotor region (MLR). This procedure, when successful, evokes "fictive locomotion," which is signaled by the recording of rhythmic bursts of discharge from motor nerves supplying the hindlimb. In addition, we sought to provide evidence that the exercise pressor reflex as well as passive stretch of skeletal muscle reset the carotid baroreflex in the decerebrate cat preparation.
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METHODS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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General Preparation
Studies were completed on 20 cats (weight = 3.6 ± 0.6 kg, means ± SD). Anesthesia was induced by inhalation of 5% halothane in O2 and maintained with 2% halothane in O2 by positive pressure ventilation through an endotracheal tube. Catheters were placed in the aorta via the right brachial artery for measurement of arterial blood pressure or sampling of blood and the right jugular vein for intravenous injections. The cats were placed in a Kopf stereotaxic frame and spinal unit and suspended over a treadmill. They were then decerebrated (22) ~2 mm rostral to the superior colliculi.The left renal artery was exposed, and care was taken to avoid damaging
the associated renal nerves. The vessel was then secured within the
housing of a calibrated transit time ultrasonic flow probe (1.5 mm;
Transonic) for measurement of renal blood flow (
ren). The abdominal wound was closed. In nine cats
in which the exercise pressor reflex was studied, a laminectomy was
performed to expose the L7-S1 dorsal and ventral roots. After immersion in warm mineral oil, the L7-S1 ventral roots were cut, and their peripheral ends were placed on a stimulating electrode.
The left knee and ankle were clamped to limit hindlimb movement. In the nine cats in which L7-S1 ventral roots were stimulated, the calcaneal bone was severed, and its tendon was fixed to a strain gauge (model FT-10, Grass) for recording of triceps surae muscle tension. The strain gauge was mounted on a rack and pinion, which permitted external application of tension to the triceps surae muscles. In the remaining cats in which the MLR was stimulated, a recording electrode was placed on a tibial nerve (see MLR stimulation).
After decerebration, anesthesia and mechanical ventilation were
discontinued, and cats were allowed to breathe room air spontaneously. Inspiratory airflow was measured by connecting a heated
pneumotachograph to the endotracheal tube. The signal was integrated
(Gould) to obtain tidal volume and then summed to obtain minute
inspiratory volume (
i). Cats paralyzed during an
experiment were ventilated mechanically with room air, and the rate and
depth of ventilation were adjusted to approximate preparalysis values.
Heart rate (HR) was derived from the pulse frequency of Pa
measurements (Gould Biotech). Intraesophageal temperature was monitored
and maintained near 37.5°C using an infrared heating lamp.
Carotid Sinus Isolation
The distal common and external carotid arteries were exposed bilaterally through a single ventral midline incision. The origin of the lingual artery from the external carotid was exposed, and ligatures were firmly tied around both vessels close to their junction. With the aid of a dissecting microscope, the occipital artery was identified on the dorsal surface of the common carotid artery and tied ~1 cm distal to its origin so that carotid body perfusion was maintained and potential confounding chemoreflex effects were avoided. A functional chemoreflex was confirmed later by observation of increased Pa after carotid sinus perfusion with cold, acidic, or deoxygenated blood at constant pressure (15). Additional smaller arterial branches of the common and external carotid arteries were also ligated on the few occasions they were visible. The internal carotid artery either is not present in the cat or is tiny (5). The integrity of the isolated vascular segment was confirmed postmortem by injection of dye into the segment under pressure and subsequent observation of complete local containment except for staining of the internal carotid artery.The segment of the common carotid artery 1 cm proximal to and distal to
the origin of the thyroid artery was carefully dissected free of the
vagosympathetic trunk. The common carotid was cannulated retrogradely
and anterogradely, and the free ends of both catheters were attached to
a single three-way tap. The tap allowed selective perfusion of the
distal common carotid with blood from either the proximal common
carotid or an external reservoir. The three-way taps from both the left
and right carotid sinus isolations were connected in parallel and then
to a precalibrated pressure transducer (model P23XL, Statham) for
measurement of carotid sinus pressure (PCS). Blood from an
external reservoir was connected in series with the pressure
transducer, thereby allowing simultaneous perfusion of both isolated
carotid sinuses at the same known pressure (Masterflex Perfusion Pump,
Cole-Palmer). When necessary, the amount of blood flowing from the
perfusion pump was increased to allow for any "leakage" into the
internal carotid artery. The pump rate, however, remained constant.
Blood in the reservoir was collected periodically in 10-ml samples from
the proximal common carotid catheter, warmed, heparinized (100 units),
and autotransfused to the carotid sinus using controlled pulsatile
pressure. The PO2 of the carotid sinus perfusate ranged between 90 and 105 mmHg. Likewise, the
PCO2 ranged between 38 and 44 mmHg, and the pH
ranged between 7.31 and 7.39. Carotid sinus pulse frequency and
amplitude were adjusted to approximate Pa characteristics
(see Fig. 1). The reproducibility and reversibility of this stimulus
within cats was confirmed by comparing throughout experiments the
PCS amplitude and frequency and the responses to
PCS changes. The physiological significance of a pulsatile stimulus was readily demonstrated by observing a pressor response whenever the pulsatile pressure was changed to a constant pressure of
equal mean value.
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Aortic Baroreceptor Denervation
With the aid of a dissecting microscope, the origin of the superior laryngeal nerve from the nodose ganglion was exposed, and the nerve containing aortic arch baroreceptors was identified by recording pulse synchronous activity from it. The nerve was severed bilaterally before it fused with the vagus. This procedure abolished more than 90% of the bradycardia evoked by intravenous injection of phenylephrine (1 µg) in unanesthetized cats with their carotid sinus circulation isolated and perfused at constant mean pressure. Vagus nerve integrity was confirmed by the observation of bradycardia in response to increases of PCS or the development of tachycardia after administration of atropine methyl bromide (1 mg/kg iv).Experimental Protocol
Approximately 1 h was allowed for the cat to equilibrate. Collection of data describing the carotid sinus baroreflex control of Pa, HR,i, and ren
was then commenced. Experiments followed one of five protocols:
1) baroreflex analysis alone; 2) baroreflex analysis while stimulating the MLR in nonparalyzed cats, a maneuver that produced actual locomotion and that will be designated as MLR
stimulation before paralysis; 3) baroreflex analysis while stimulating the MLR during paralysis, a maneuver that produced fictive
locomotion; 4) baroreflex analysis during electrical
stimulation of L7-S1 ventral roots, a maneuver that statically
contracted the hindlimb muscles; and 5) baroreflex analysis
during passive stretch of the triceps surae muscles to a tension equal
to that induced by L7-S1 ventral root stimulation.
Baroreflex stimulation. In each experiment, baroreflex data points were obtained by initially holding PCS to a mean value of ~100 mmHg for 1 min to allow other variables to stabilize. The treatment (no stimulation, MLR stimulation, ventral root stimulation, or muscle stretch) was then commenced. After 30 s, the carotid sinus baroreflex was manipulated by rapidly (<3 s) raising or lowering PCS. The new PCS was maintained for ~30 s before being returned to control, and the treatment was discontinued. A total of seven data points were collected describing the response to raising and lowering PCS by zero (i.e., no change), by ~30 mmHg, by ~60 mmHg, and by ~90 mmHg.
MLR stimulation. A monopolar stimulating electrode was guided into the MLR using stereotaxic coordinates as described by Eldridge et al. (9). The criteria for correct positioning of the electrode was the appearance of coordinated locomotion accompanied by increases in Pa and HR (9). The MLR was stimulated with 10-150 µÅ current for 0.75 ms at a frequency of 35-70 Hz using a Grass 88 stimulator. Actual locomotion was evoked by stimulation in the unparalyzed state, whereas fictive locomotion was evoked by stimulation in the paralyzed state, which was induced by pancuronium bromide (0.1 mg/kg). The criteria for the successful elicitation of central command was that stimulation of the MLR evoked rhythmic bursts of discharge from the tibial nerve in paralyzed cats.
L7-S1 ventral root stimulation and passive stretch of triceps surae muscles. The L7 and S1 ventral roots were stimulated in each cat at no more than three times motor threshold (0.1 ms; 20-40 Hz). In each cat, the passive muscle stretch was applied at a tension equal to that evoked by ventral root stimulation. Resting tension was set at 0.5 kg.
Data Collection and Analysis
In all protocols, Pa, HR,ren,
i, and PCS data were collected in
control and response pairs. The control data were defined as the
average values of a parameter in the 5 s preceding a treatment intervention, and the response data were the average values 25 s
after treatment had commenced. This allowed collection of data describing the steady-state hemodynamic response after acute reflex adjustments were completed. Renal conductance (Cren) was
calculated as the quotient of ren and
Pa.
The control and response data were compared using repeated measures ANOVA. Where appropriate, comparisons between control and response data were made with Bonferroni tests.
The effect of each treatment on baroreflex control of Pa,
HR, ren, Cren, and i
was examined by plotting graphs of each parameter versus
PCS. All data for all cats collected within a given
protocol were plotted on the same graph. With the exception of
Pa, attempts to fit the data to a sigmoidal function were
not successful (see Sigmoidal Function Analysis). This
caused us to analyze the data in two ways. First, separate linear
regression lines for each treatment were fitted to all the data. Over
the range of PCS tested, linear regression analysis
permitted approximation of the linear portion of characteristic sigmoid
baroreflex curves while simplifying subsequent statistical
calculations. Regression coefficients and elevations of each treatment
were compared using analysis of covariance (ANCOVA). Multiple
comparisons between treatment elevations were made using Tukey
adjustments. Second, for Pa data, sigmoidal functions were
fitted for each of the treatments. These plots allowed us to determine
if the treatments shifted the curves laterally or vertically. This
comparison was made using either a paired t-test or a
repeated measures ANOVA.
Values presented are means ± SE. Statistical analyses were carried out on absolute values before conversion to percentages. All detected differences were significant if P < 0.05.
To assess the potential for misinterpretation of HR data due to the hyperbolic relationship between HR and R-R interval, HR was also converted to heart period and all analyses described for HR were repeated using heart period. The results and their interpretation after analysis of heart period data were the same as those obtained for HR. Therefore, only HR data are presented.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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Response to Electrical Stimulation of MLR
MLR stimulation before paralysis raised Pa, HR, andi and decreased ren and
Cren (Fig. 1). On average,
MLR stimulation raised Pa to 191%, HR to 124%, and
i to 138% of control and lowered Cren
to 41% (all P < 0.05 compared with control; Fig. 2). ren fell in eight of nine animals to
an average of 81% of control, but this change was not statistically
significant. Coordinated walking over the treadmill was observed in the
three nonfixed limbs and was associated with synchronization between
hindlimb muscle contractions and tibial electroneurogram (ENG)
activity. PCS was fixed at 92 ± 2.4 mmHg and was
unchanged by MLR stimulation.
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Paralysis alone (Fig. 2) raised
baseline HR to 112% of control (P < 0.05 compared
with unparalyzed HR) but had no effect on Pa,
PCS, ren, or Cren (all
variables P > 0.05). It also abolished spontaneous
ventilation and muscle movement, but ENG activity was still present.
The hemodynamic response to MLR stimulation after paralysis was
qualitatively similar to the response before paralysis (Figs. 1 and 2).
On average, Pa and HR increased to 183 and 109% of
control, respectively (both P < 0.05),
Cren decreased to 56% (P < 0.05), and
PCS and ren did not change. Paralysis
also had no effect on the magnitude of the Pa and
Cren responses to MLR stimulation (P > 0.05 for comparison of changes in unparalyzed and paralyzed states).
However, paralysis approximately halved the HR response and abolished
the ren and i responses
(P < 0.05 for comparison of changes in unparalyzed and
paralyzed states), the latter being due to the fact that the lungs were
ventilated mechanically.
MLR stimulation during paralysis also was accompanied by phasic increases of ENG amplitude (frequency ~2 Hz) characteristic of fictive locomotion (9). The bursts of ENG activity were mostly visible on the oscilloscope and chart recorder (Fig. 1). On occasions when background noise of the ENG recording obscured visual detection, phasic ENG activity was confirmed audibly.
Response to Carotid Sinus Pressure Change
In all cats, the hemodynamic effects of raising and lowering PCS were consistent with baroreflex control of the circulation (Figs. 1 and 3). For example, raising PCS to 150% of control decreased Pa to 85%, HR to 97%, andi to 93% of control (all
variables: slope P < 0.05 compared with zero slope).
Equal but opposite changes were evoked by lowering PCS.
Both ren and Cren did not change over
the range of PCS tested (slope P > 0.05 compared with zero slope).
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Effects of MLR Stimulation on Carotid Sinus Baroreflex
Slope of baroreflex curves.
The slopes of the Pa and HR versus PCS curves
were not changed by paralysis alone, MLR stimulation before paralysis,
or MLR stimulation during paralysis (P > 0.05 for
ANCOVA comparison of regression coefficients), indicating preserved
baroreflex control during real and fictive locomotion (Fig. 3).
Similarly, the slope of the ren versus
PCS curve was not changed by either treatment (P > 0.05 for ANCOVA comparison of regression
coefficients). The slopes of all ren versus
PCS curves were statistically indistinguishable from zero slope.
i versus PCS curve was not changed by
MLR stimulation but became zero after paralysis and MLR stimulation
after paralysis due to imposed mechanical ventilation (Fig. 3).
Elevation of baroreflex curves. MLR stimulation before paralysis raised the curve describing carotid sinus baroreflex control of Pa to 167% of its control position (P < 0.05 for ANCOVA comparison of elevations). However, MLR stimulation during paralysis raised the Pa versus PCS curve to 148% of its control position (P < 0.05), an effect representing a significantly smaller upward shift than that in the unparalyzed state (P < 0.05). The Pa versus PCS curves obtained before and after paralysis alone (no MLR stimulation) were similar (P > 0.05).
MLR stimulation before paralysis raised the entire HR versus PCS curve to 123% of its control position (P < 0.05). MLR stimulation during paralysis also raised the HR versus PCS curve. This upward shift was to 106% of the curve obtained after paralysis alone (P < 0.05). The final position of the HR versus PCS curves obtained during MLR stimulation before paralysis and MLR stimulation during paralysis were the same (P > 0.05) despite a significant effect of paralysis alone on the baroreflex control of HR. The HR versus PCS curve obtained during paralysis alone was raised to 112% of that obtained in the absence of paralysis. The elevations of Cren versus PCS curves obtained during MLR stimulation before paralysis and MLR stimulation during paralysis were lowered to 51 and 67%, respectively, of the curve obtained in the unparalyzed state. Both curves were equally lowered (P > 0.05), and paralysis alone had no effect on the Cren versus PCS relationship (P > 0.05). In contrast, the elevation of theren versus PCS curve was not changed by
paralysis alone, by MLR stimulation before paralysis, or by MLR
stimulation after paralysis (P > 0.05).
MLR stimulation before paralysis raised the entire
i versus PCS curve to 144% of its
control position (P > 0.05). The elevations of curves
obtained during paralysis and during MLR stimulation while paralyzed
were equal; both were also less than elevations of the curves obtained
during control conditions and MLR stimulation before paralysis.
Response to Ventral Root Stimulation
Electrical stimulation of the ventral roots caused immediate tetanic contraction of the triceps surae muscles, producing a peak tension of 4.0 ± 0.3 kg, which gradually halved over the next minute. Pa and HR rose to 145 and 117% of control, respectively (both P < 0.05),ren,
i and PCS did not change (all
P > 0.05), and Cren fell to 72% of
control (P < 0.05; Figs.
4 and
5). These effects were abolished by
paralysis and sectioning L7-S1 dorsal roots.
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Effects of Ventral Root Stimulation on Carotid Sinus Baroreflex
The slopes of curves for all measured variables during ventral root stimulation were unchanged (all variables: P > 0.05 for comparison of slopes in absence and presence of ventral root stimulation), indicating functional preservation of hemodynamic control mechanisms during muscle contraction (Fig. 6). The Pa and HR versus PCS curves were raised to 135 and 112%, respectively, of their control positions (both variables: P < 0.05). In contrast, the Cren versus PCS curve was lowered to 80% of its control position (P < 0.05). The elevation ofren and i versus
PCS curves were not changed by ventral root stimulation
(both variables: P > 0.05).
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Response to Muscle Stretch
Stretch of the triceps surae muscles increased Pa to 126% of control (P < 0.05) and HR to 105% of control (P < 0.05). Stretch had no effect on eitherren and i (both P > 0.05; Figs. 4 and 5). Stretch decreased Cren to 73% of
control (P < 0.05) but had no effect on
PCS (P > 0.05). Paralysis had no effect on
the responses to stretch, whereas sectioning of the L7-S1 dorsal roots abolished them. During stretch, the tension applied to the calcaneal tendon was constant and averaged 4.0 ± 0.4 kg. Baseline tension averaged 0.5 ± 0.1 kg.
Effects of Muscle Stretch on Carotid Sinus Baroreflex
Muscle stretch had similar effects on the baroreflex control of Pa, HR, Cren,ren, and
i as those evoked by static contraction (Fig. 6).
The slopes of Pa, HR, Cren,
ren, and i versus PCS curves were unchanged (all variables: P > 0.05).
Pa and HR versus PCS curves were raised to 111 and 112% of control positions, respectively (both variables:
P < 0.05). The Cren versus PCS
curve was lowered to 85% of its control position (P < 0.05), and the elevations of ren and
i versus PCS curves were unchanged
(P > 0.05).
Sigmoidal Function Analysis
We were able to fit Boltzman sigmoidal curves to the data relating Pa to PCS during MLR stimulation (i.e., central command), during calcaneal tendon stretch, and during contraction of the triceps surae muscles (Fig. 7). With the use of a midpoint analysis, we found that central command significantly shifted (P < 0.01) the midpoint of the baroreflex function curves vertically but not laterally (Table 1). Likewise, contraction significantly shifted (P < 0.01) the midpoint of the curves vertically but not laterally (Table 1). Tendon stretch, however, did not shift the midpoint of the baroreflex function curve either vertically or laterally (P > 0.05; Table 1).
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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This study demonstrated that central command, in isolation, can reset the carotid sinus baroreflex. MLR stimulation, which evoked fictive locomotion in decerebrate cats, translated the curves describing the carotid sinus baroreflex control of Pa and HR to higher Pa and HR values, respectively. Likewise, MLR stimulation translated the curve describing baroreflex control of renal vascular conductance to lower Cren values. This means that during activation of central command, the baroreflex control of Pa, HR, and Cren is maintained with equal sensitivity to that of the resting state but is adjusted to operate at higher (Pa and HR) or lower (Cren) levels.
These findings directly support hypotheses made by two groups of investigators studying barodenervated conscious exercising rabbits. Ludbrook and colleagues (16, 17) speculated that the observed blunting of hemodynamic control mechanisms may be the result of central command interacting with the baroreflex. Similarly, DiCarlo and Bishop (6) and Rowell and O'Leary (25) speculated that central command causes the upward shift in operating point of baroreflex control of mean arterial pressure during exercise. Although each of these authors has hypothesized a role of central command in baroreflex resetting, definitive evidence confirming or refuting their hypothesis was not presented. Recently, Iellamo et al. (12) attempted to isolate the effect of central command on baroreflex resetting during exercise in humans. They found that excluding central command from an exercise protocol decreased the sensitivity of the relationship between systolic arterial pressure and pulse interval. Although this finding is consistent with a role played by central command in resetting the baroreflex during exercise, it is not the equivalent of directly examining the effect of central command (i.e., fictive locomotion) on this reflex.
At first glance, our finding that central command reset both the HR and
Pa components of the baroreflex might appear to differ somewhat from that of Bauer et al. (2), who reported that
central command reset the cardiac but not the arterial pressure
component of this reflex. Several factors may explain this difference.
First, we electrically stimulated a locomotor region of the midbrain, whereas Bauer et al. (2) chemically stimulated the
posterior hypothalamus, an area that evokes the defense reaction
(1, 4). Second, we evoked fictive locomotion, whereas
Bauer et al. (2) did not report whether or not this
occurred. Third, we used decerebrate unanesthetized cats, whereas Bauer
et al. (2) used intact 
-chloralose-anesthetized
cats. Because of these differences, any comparison of our
findings with those of Bauer et al. (2) is not likely to
be useful.
Collection of data during neuromuscular blockade in the present study
required evaluation of the effects of paralysis on the observed
responses. All responses to both baroreflex activation and MLR
stimulation were unchanged by paralysis, with the exception of
i and HR responses (Figs. 2 and 3). Both of these
used cholinergic mechanisms and were therefore susceptible to the
anticholinergic paralytic agent pancuronium bromide. Although baseline
HR was elevated by the paralytic agent, the sensitivity (slope) of the HR versus PCS curve was unchanged. This suggests that, like
control of Pa and Cren, the sensitivity of
baroreflex control of HR was unaffected by pancuronium bromide.
Prior studies of baroreflex control established the importance of a pulsatile pressure stimulus on baroreflex function. In both dogs (27) and cats (7) with isolated carotid sinus circulations, depulsation of PCS with maintenance of the mean pressure produces a pressor response characteristic of baroreceptor unloading. A similar response was observed in the present study. This not only confirms the integrity and sensitivity of the baroreflex after preparation but also reinforces the importance of having matched both pulse frequency and amplitude to resting values in all cats. The stimulus to the baroreceptors in the present study was also reproducible and reversible, ensuring a constant, controlled, and nondeleterious intervention that did not interfere with results. In addition, comparison within cats of the response to a given PCS change at the beginning and end of each experiment showed that the direction and magnitude of changes were predictable, that the response did not deteriorate with time, and that all values returned readily to control values after restoration of PCS to control (Figs. 1 and 4).
Our findings are consistent with those of Potts and Mitchell
(23), who experimented on -chloralose-anesthetized
vagotomized dogs whose isolated carotid sinus circulations were
perfused by nonpulsatile pressure. By slowly raising the carotid sinus
perfusion pressure from 50 mmHg, they determined that the threshold
PCS at which Pa and HR began to fall was
elevated by both passive hindlimb muscle stretch and by hindlimb
muscular contraction. Potts and Mitchell (23) hypothesized
that "baroreflex resetting" was responsible for their results. Our
findings extend those of Potts and Mitchell (23) because
they describe data over a wide physiological range of PCS
and therefore represent a more complete demonstration of baroreflex
resetting (27). In addition, our findings represent a more
natural situation than that used by Potts and Mitchell
(23) because we raised and lowered PCS from a
"normotensive" physiological level, i.e., 100 mmHg. Moreover, we
used pulsatile pressure to stimulate carotid baroreceptors, whereas
Potts and Mitchell (23) used nonpulsatile pressure to stimulate these receptors.
The conclusion that muscle afferent input can reset the carotid sinus baroreflex control of Pa, HR, and Cren assumes that electrically induced muscle contraction activated group III and IV muscle afferents. This is well known to be the case (13, 14). Specifically, static muscle contraction is known to activate group III and IV muscle afferents responsive to both mechanical and metabolic stimuli (13, 14). Moreover, activation of these thin fiber afferents produced similar hemodynamic responses to those observed in the present study (13, 18). In addition, contraction was performed after L7-S1 dorsal root sectioning, a procedure that abolished the previously evoked effects. The responses to muscle contraction were also abolished by paralysis, thereby obligating muscle contraction as the initiating event of the cardiovascular responses evoked by electrical stimulation of the ventral roots.
The close circulatory proximity of carotid body chemoreceptors to
carotid sinus baroreceptors presented an additional consideration to
the quality of the baroreflex stimulus. Indeed, the potential for
confounding effects was highlighted by the demonstration that characteristic chemoreflex effects of simultaneously increased Pa and i could be evoked by perfusing
the carotid sinus with acidic or hypoxic blood (15). This
showed that the chemoreceptors and chemoreflex pathways remained intact
in this preparation. Despite this, these effects were not observed
during the experiment when the carotid sinus perfusate was carefully
controlled. It is therefore unlikely that the observed responses were
contaminated by the carotid body chemoreflex.
In our experiments, neither static contraction nor muscle stretch translated the curves describing carotid baroreflex control of ventilation to higher values. In contrast, MLR stimulation before paralysis shifted this curve upward. Although we cannot rule out the possibility that resetting of ventilation required the interaction of both central command and the exercise pressor reflex, the simplest conclusion is that MLR stimulation alone is responsible for the upward resetting of baroreflex control of ventilation. This conclusion must be considered as speculation because we did not record phrenic nerve discharge, an index of ventilation when the cats were paralyzed (8). Finally, any conclusion that the exercise pressor reflex does not reset the ventilatory component of the baroreflex must be tempered by the fact that the static contractions used in our experiments were modest, developing active or passive tensions that averaged only about one-third of the maximum for the triceps surae muscles of cats (33, 34).
Our conclusion that both central command and the exercise pressor reflex "reset" the baroreflex needs to be clarified. Sagawa (27) described an upward shift of the baroreflex curve as "reference resetting" and attributed this effect to a secondary input. With reference resetting the baroreceptor reflex continues to operate normally in the face of a second input (e.g., central command or the exercise pressor reflex) that increases the output variables uniformly across the full range of PCS. In contrast to reference resetting, Sagawa (27) also described "receptor resetting," which is a lateral shift of the baroreflex curves. In our experiments, we found evidence that the sigmoidal relationship between PCS and mean arterial pressure was shifted upward but not laterally. These findings suggest that central command and the exercise pressor reflex caused reference resetting of the baroreflex.
Tendon stretch is well established to reflexively increase Pa and HR by stimulating group III mechanoreceptors in skeletal muscle (29, 33). Despite the fact that these reflex responses were evoked by tendon stretch in our experiments, this maneuver caused minimal if any baroreflex resetting. Specifically, tendon stretch significantly shifted the baroreflex function curve upward when the data were analyzed linearly, but the magnitude of the effect was quite modest. Alternatively, tendon stretch did not significantly shift the baroreflex curve upward when the data were analyzed as a sigmoidal function. Taken together, these findings suggest that group III mechanoreceptors probably play little if any role in baroreflex resetting in exercise. Nevertheless, one qualification needs to be mentioned: namely, that the tension developed by tendon stretch in our experiments was not large, averaging only 3.5 kg. More severe tendon stretch might lead to a different conclusion about the relationship between baroreflex resetting and stimulation of group III mechanoreceptors.
In summary, the present study has shown, for the first time, that activation of central command in decerebrate cats can reset the carotid sinus baroreflex control of Pa, HR, and Cren. Likewise, a similar role has been demonstrated for the exercise pressor reflex. Although the precise mechanisms of these interactions are unknown, resetting probably occurs rapidly at the start of exercise and most likely is initiated by central command. Once the muscles have started to contract, the exercise pressor reflex most likely contributes to resetting as well.
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ACKNOWLEDGEMENTS |
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The authors thank Dr. J. Legramante and Dr. A. Degtyarenko for scientific consultation, P. Walgenbach and E. English for assistance with preparation of the manuscript, and N. Moya del Pino and K. Tamojian for technical assistance.
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FOOTNOTES |
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This study was supported by National Heart, Lung, and Blood Institute Grant HL-30710.
Address for reprint requests and other correspondence: M. P. Kaufman, Div. of Cardiovascular Medicine, TB 172, One Shields Ave., Davis, CA 95616 (E-mail: mpkaufman{at}ucdavis.edu).
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 12 March 2000; accepted in final form 31 October 2000.
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REFERENCES |
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TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
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, Control conditions;
, MLR stimulation in unparalyzed cats;
, MLR stimulation in paralyzed cats.
, either
tendon stretch or contraction.
, either tendon stretch or
contraction.