Role of central command in carotid baroreflex resetting in humans during static exercise

Authors


Abstract

The purpose of the experiments was to examine the role of central command in the exercise-induced resetting of the carotid baroreflex. Eight subjects performed 30 % maximal voluntary contraction (MVC) static knee extension and flexion with manipulation of central command (CC) by patellar tendon vibration (PTV). The same subjects also performed static knee extension and flexion exercise without PTV at a force development that elicited the same ratings of perceived exertion (RPE) as those observed during exercise with PTV in order to assess involvement of the exercise pressor reflex. Carotid baroreflex (CBR) function curves were modelled from the heart rate (HR) and mean arterial pressure (MAP) responses to rapid changes in neck pressure and suction during steady state static exercise. Knee extension exercise with PTV (decreased CC activation) reset the CBR-HR and CBR-MAP to a lower operating pressure (P < 0.05) and knee flexion exercise with PTV (increased CC activation) reset the CBR-HR and CBR-MAP to a higher operating pressure (P < 0.05). Comparison between knee extension and flexion exercise at the same RPE with and without PTV found no difference in the resetting of the CBR-HR function curves (P > 0.05) suggesting the response was determined primarily by CC activation. However, the CBR-MAP function curves were reset to operating pressures determined by both exercise pressor reflex (EPR) and central command activation. Thus the physiological response to exercise requires CC activation to reset the carotid-cardiac reflex but requires either CC or EPR to reset the carotid-vasomotor reflex.

The effect of exercise on the gain of the arterial baroreflex and its functionality have intrigued many investigators since the 1960s (Bevegard & Shepherd, 1966; Robinson et al. 1966; Bristow et al. 1971; Cunningham et al. 1972; Pickering et al. 1972; Ludbrook et al. 1977; Ludbrook et al. 1978; Mancia et al. 1978). However, the findings of these earlier studies were equivocal as to whether baroreflexes were reset or became inactive during exercise. More recently, a number of investigations in humans (Ebert, 1986; Potts et al. 1993; Papelier et al. 1994; Iellamo et al. 1997; Norton et al. 1999) have demonstrated that the arterial baroreflex is reset and continues to operate around the prevailing blood pressure generated during physical activity. This resetting occurs in direct relation to the intensity of the exercise from rest to maximal workloads (Potts et al. 1993; Papelier et al. 1994; Norton et al. 1999). The rapidity of the resetting (DiCarlo & Bishop, 1992) and the involvement of the nucleus tractus solitarius (Mifflin & Felder, 1990; Hasser et al. 1997; Paton et al. 2001; Potts, 2001) as a site of integration for descending cortical outflow (central command) and peripheral receptor input (exercise pressor reflex) identifies a possible central neural mechanism for arterial baroreflex resetting linked to the activation of central command.

Recently, we selectively augmented the influence of central command during steady state static and dynamic leg exercise using partial neuromuscular blockade (norcuron; Gallagher et al. 2001b). In addition, Querry et al. (2001) reduced exercise pressor reflex input while augmenting central command activation during static and dynamic arm exercise by inducing partial axillary neural blockade (lidocaine). Augmentations in central command in both studies resulted in increases in heart rate (HR) and mean arterial blood pressure (MAP) as well as rightward and upward (i.e. parallel) resetting of the carotid baroreflex function curves for both heart rate (CBR-HR) and mean arterial blood pressure (CBR-MAP). However, within these investigations, it remains unclear whether neuromuscular blockade activated undefined central neural pathways associated with increased subject anxiety. Activation of such neural circuitry could contribute to the physiological responses elicited.

In cats, Potts & Mitchell (1998) demonstrated that activation of metabolically and mechanically sensitive skeletal muscle afferent fibres resets the carotid baroreflex. Likewise, McIlveen et al. (2001) demonstrated that selectively stimulating: (i) the mesencephalic locomotor region (a site potentially involved in central command signalling); (ii) statically contracting the triceps surae muscle (activation of the exercise pressor reflex); or (iii) stretching the hindlimb muscle (activation of the skeletal muscle mechanoreflex) reset the carotid baroreflex to higher operating pressures in cats. These findings in animals complement those recently described in humans (Gallagher et al. 2001a,b; Querry et al. 2001).

By using tendon vibration to assist or to oppose an exercising muscle group while developing a given force one can decrease (agonist activation) or increase (antagonist inhibition) the influence of central command without inducing nociceptor afferent input or augmenting normal exercise pressor reflex activation (Goodwin et al. 1972). Using this technique in combination with non-invasive baroreflex testing (i.e. neck pressure/suction), we investigated the role of central command in the resetting of the carotid baroreflex.

Methods

Subjects

Eight subjects (4 men and 4 women, means ±s.e.m.: age, 26.6 ± 1.1 years; height 171.8 ± 3.7 cm; weight, 72.9 ± 6.3 kg) were recruited for voluntary participation in the present study. All subjects were free of known cardiovascular and pulmonary disorders, were normotensive non-smokers and were not taking prescribed or over-the-counter medications. Written informed consent was obtained from all subjects and the study protocol was approved by the University of North Texas Health Science Centre Institutional Review Board for the use of human subjects in conformation with the declaration of Helsinki. Prior to each experimental day, the subjects were asked to abstain from caffeinated beverages for a minimum of 12 h and from strenuous physical activity for 24 h.

Muscle spindle stimulation (vibration)

A physiotherapy vibrator (Shiatsu-Accu-Tap II, Panasonic, Osaka, Japan) was used to induce muscle contraction by activation of the patellar tendon reflex. In the present investigation the oscillating vibration was applied to the patellar tendon while the subjects performed sustained isometric contractions of the quadriceps or the hamstrings. The vibrator's oscillating frequency was selected to elicit a maximal patellar tendon reflex for each subject (4.5 ± 0.4 Hz). Patellar tendon vibration during quadriceps contraction (i.e. agonist vibration) aided tension development and, therefore, lessened the amount of central command required. Conversely, patellar tendon vibration during hamstring contraction (i.e. antagonist vibration) produced disynaptic inhibition of motoneurons innervating the active muscles and, as a result, increased the central command requirement for force generation (Goodwin et al. 1972).

Exercise protocol

On the first day, subjects performed three maximal static 90 deg knee angle extensions (quadriceps muscle exercise) and flexions (hamstring muscle exercise) of the dominant leg to determine maximal voluntary contraction (MVC). After the MVC trials, the subject was familiarized with the experimental protocol, the physiological measurements to be obtained and the carotid baroreflex testing procedures.

Study 1

On a second day, subjects (n= 8) performed static knee extension and flexion with and without patellar tendon vibration. The subjects were seated in an exercise chair equipped for static knee extension or flexion from a 90 deg knee angle. After a preliminary 30 min resting period in the upright seated position, each subject performed the same protocol under four different conditions: (i) knee flexion, (ii) knee extension, (iii) knee flexion with patellar tendon vibration and (iv) knee extension with patellar tendon vibration. The protocol consisted of a 5 min resting control period followed by 3 min of static contraction at 30 % of the subject's pre-determined MVC completed by a 2 min recovery period. All exercise bouts were randomized and separated by a minimum of 30 min.

Study 2

On a third day, subjects (n= 7) performed exercise at a workload that elicited the same ratings of perceived exertion (RPE, an index of central command activity) as those obtained during Study 1. As a result, static knee extension was performed at 22.6 ± 13 % MVC while the knee flexion protocol required subjects to work at 41.0 ± 2.4 % MVC. These intensities were determined for each subject using the Borg scale (Borg, 1982) value obtained during the initial 30 % MVC extension or flexion exercise with patellar tendon vibration. All exercise protocols and measurements were the same for both investigations. A diagrammatic representation of the exercise is presented in Fig. 1.

Figure 1.

Experimental designs of Study 1 (I and II) and Study 2 (II and III)

A, knee extension at : (I) 30 % MVC; (II) 30 % MVC with applied vibration (agonist patellar tendon vibration) and (III) 22.6 % MVC. Vibration was used to excite the primary afferents of the muscle spindles of the contracting muscle. Thereby agonist vibration contributed an element of reflex excitation to the motoneurones innervating the contracting quadriceps. Study 1 (I and II), during trial II less central command was required (+++→++) to achieve the same tension as trial I (30 % MVC) because of the reflex excitation associated with the agonist patellar tendon vibration. Study 2 (II and III), during trial III less intensity (22.6 % MVC) was required (+++→++) to adjust the RPE to the same of that recorded during the 30 % MVC force plus vibration of trial II. B, knee flexion at: (I) 30 % MVC; (II) 30 % MVC with applied vibration (vibration of an antagonistic muscle) and (III) 41.0 % MVC. Vibration of the antagonist quadriceps muscle groups contributed an element of reflex inhibition to the motoneurones innervating the contracting hamstrings. Study 1 (I and II), during trial II greater central command was required (+++→++++) to achieve the same tension as trial I (30 % MVC) because of reflex inhibition accompanied by vibration of an antagonistic muscle. Study 2 (II and III), during trial III (the greater tension, 41.0 % MVC) the hamstring muscle group work was required (+++→++++) to achieve the same RPE of that recorded in trial II.

Static knee exercise was accomplished by pushing the dominant leg against a fixed metal bar connected to a strain gauge dynamometer (DP41-S-A, Omega Engineering Inc., Stanford, CA, USA) wrapped around the subject's ankle. The subjects were encouraged to maintain constant muscular activity through visual feedback from a monitor displaying their force. Heart Rate (HR) and mean arterial pressure (MAP) data were collected continuously throughout the experiment. Two carotid baroreflex function (CBR) curves using rapid changes in neck collar pressure (Pawelczyk & Raven, 1989) were performed between minutes two and three of each contraction.

Measurements

During Study 1 the subject's HR was recorded from a standard lead II electrocardiogram (ECG) and arterial blood pressure was obtained from a radial, brachial, or femoral (non-dominant arm or leg) arterial catheter inserted by a consultant cardiologist or cardiothoracic surgeon. The site of catheterization was determined by the physician on a case-to-case basis. Blood pressure was transduced using a sterile, disposable pressure transducer (Maximum Medical, Athens, TX, USA) and tubing kit (Cobe, Lakewood, CO, USA). The computer interface (model 78342A, Hewlett-Packard, Andover, MA, USA) integrated the pressure transducer signal for systolic, diastolic and mean arterial blood pressure (MAP). During Study 2 arterial blood pressure was measured non-invasively on a continuous basis using finger photoplethysmography (Finapres, Ohmeda, Madison, WI, USA). Diastolic blood pressure recordings of the finapres were matched with diastolic blood pressure obtained by brachial auscultation before recordings were started. In addition, individual RPEs were obtained at the end of each minute of exercise using the Borg scale (Borg, 1982).

During each exercise test, the subjects breathed through a sterilized mouthpiece attached to a turbine volume transducer (model VMM Modem 2A, SensorMedics, Anaheim, CA, USA) and a sampling port for a mass spectrometer (model MGA1100B, Perkin-Elmer, St. Louis, MO, USA) to determine O2 uptake. Device input signals underwent analog-to-digital conversion for on-line breath-by-breath determination. Standardized calculations of metabolic data were corrected for ambient conditions.

Carotid baroreflex function curves

Carotid baroreflex control of HR and MAP was evaluated using a neck pressure/neck suction (NP/NS) technique. Pressure stimuli were accomplished by applying NP/NS using a flexible lead collar wrapped around the anterior two-thirds of the subject's neck. This collar was modified from the design previously described by Eckberg et al. (1975). In this method, pressure and suction were delivered from commercial vacuum motors and timed using large bore (2.5 cm i.d.), two-way solenoid valves (Model 8215B, Asco, Florham Park, NJ, USA). Due to the brevity of the exercise protocol, carotid baroreceptor stimulation was conducted using rapid changes in the neck collar pressures (Pawelczyk & Raven, 1989). The protocol of the rapid pulse train was comprised of twelve pulsed pressures ranging from +40 to −80 mmHg of 500 ms duration. Each pulse was computer-controlled to deliver the NP/NS pulse to the carotid sinus precisely 50 ms after initiation of the R-wave detected by ECG. Between each pressure pulse the neck chamber pressure was vented to atmospheric pressure by computer control to create a pulsatile stimulus. The generated neck collar pressure applied to the carotid sinus region was measured by a pressure transducer (model DP45, Validyne Engineering, Northridge, CA, USA). The NP/NS pulse train was conducted during a 10 to 15 s breath-hold at end-expiration to minimize the respiratory-related modulation of HR and MAP (Eckberg, 1976). Two rapid pulse trains were applied during static exercise with a minimum of 45 s of recovery between pulse trains. Pulse trains of NP/NS were also performed at rest before each exercise bout.

The beat-to-beat responses of HR and MAP were recorded along with the chamber pressure measured within the neck collar. Estimated changes in carotid sinus pressure (CSP) were calculated as MAP minus the neck chamber pressure. The CBR stimulus-response curve was defined as the nine-beat data period corresponding to the four positive-pressure pulses and five negative-pressure stimuli. The nine-beat HR and MAP responses that best represented the peak reflex response range were selected and aligned with the calculated CSP to complete the stimulus-response data set.

Data and statistical analysis

The carotid HR and the carotid MAP responses were evaluated by plotting the peak changes in HR and MAP against estimated CSP, respectively. Each carotid baroreflex stimulus-response curve was fitted to the logistic model described by Kent et al. (1972). This function incorporates the following equation:

HR or MAP =A1{1 + exp[A2(ECSP –A3)]}−1+A4,

where HR or MAP is the dependent variable, ECSP is the estimated carotid sinus pressure, A1 is the range of response of the dependent variable (maximum – minimum), A2 is the gain coefficient (i.e. slope), A3 is the carotid sinus pressure required to elicit equal pressor and depressor responses (centring point), and A4 is the minimum response of HR or MAP. The gain was calculated from the first derivative of the logistic function and the maximal gain (Gmax) was applied as the index of carotid baroreflex responsiveness. Threshold CSP (CSPthr), the point where no further increase in the dependent variable occurred despite reductions in ECSP and saturation CSP (CSPsat), the point where no further decrease in the dependent variable occurred despite increases in ECSP, were calculated as the maximum and minimum second derivatives, respectively, of the logistic function curve. For calculation of CSPthr and CSPsat, we applied equations described by Chen & Chang (1991): CSPthr=−2.0/A2+A3 and CSPsat= 2.0/A2+A3. These calculations of CSPthr and CSPsat have been found to be the carotid sinus pressure at which MAP or HR are within 5 % of their maximal or minimal responses.

Data are expressed as mean ± the standard error of the mean (s.e.m.). A two-way analysis of variance (ANOVA) with repeated measures was employed to determine significant differences at rest, recovery and static exercise. Comparison of CBR parameters were analysed using a one-way ANOVA with repeated measures. If significance was found, a Student Newman-Keuls post hoc test was employed to establish significant group mean differences. In addition, Student's paired t test was used for individual comparisons. Statistical significance was set at P < 0.05. Analyses were conducted using SigmaStat for Windows (SPSS Inc., Chicago, IL, USA).

Results

Vibration to the patellar tendon elicited a reflex tension in the quadriceps muscle. In this study, the average of this tension was 9.6 ± 1.8 % of the maximum knee extension tension of which the subject was capable. However, the vibration to the patellar tendon did not cause a significant increase or decrease in the resting HR or MAP when the vibration condition was compared with the control; i.e. HR 65.7 ± 3.3 vs. 63.8 ±2.9 beats min−1 (P= 0.364) and MAP 86.8 ± 2.3 vs. 88.2 ± 2.2 mmHg (P= 0.243).

Effects of patellar tendon vibration (PTV) during static exercise

The subjects reported that during knee extension with PTV a decreased effort was required. During knee flexion with PTV an increased effort was required to maintain the same absolute force as when performing the exercise without PTV. These subjective responses were reflected in each subject's RPE. A comparison of RPE is shown in Fig. 2A and 2D. The RPE of knee extension with PTV was significantly decreased from 14.0 ± 0.9 during control extension to 12.4 ± 0.9 (P < 0.01) at the third minute of exercise. During knee flexion at 30 % MVC the subjects' RPE were significantly increased during PTV. The RPE increased from 11.1 ± 0.5 to 13.4 ± 0.8 (P < 0.01) at the third minute of exercise. The HR responses recorded at rest and during the 3 min of static knee extension and flexion with and without the PTV are shown in Fig. 2B and 2E, respectively. The HR obtained a steady state value without additional elevations during the first minute of static extension and flexion exercise with and without PTV. The HR response to static knee extension was decreased by 4.1 ± 1.6 beats min−1 at the third minute with PTV compared with the control extension exercise throughout (P < 0.05). Conversely, during static knee flexion the HR was elevated by 5.8 ± 1.6 beats min−1 at the third minute when PTV was applied (P < 0.05). The MAP responses to static knee extension and flexion are shown in Fig. 2C and 2F, respectively. MAP increased linearly throughout static knee extension and flexion with and without PTV. The effect of the PTV on MAP responses was similar to that observed for the HR responses. There was a decrease in MAP of 9.9 ± 3.7 mmHg at the third minute during knee extension with the PTV compared with the extension exercise without PTV (P < 0.001). Conversely, the MAP response to static knee flexion was increased by 11.9 ± 3.4 mmHg at the third minute with PTV compared with flexion exercise without PTV (P < 0.001). Oxygen uptake (VO2) increased significantly throughout static knee extension and flexion with and without PTV (Table 1). However, there was no significant difference between with and without PTV during static knee extension at 30 % MVC. Because the VO2 was not different during the exercise with PTV compared to the exercise without PTV (Table 1) it was concluded that the vibration technique did not alter the absolute muscle tension during the static extension exercise bouts. However, the VO2 during knee flexion was increased by PTV (P < 0.05). We suggest that because the amplitude of the electromyographic activity (EMG) of the hamstring muscle group during flexion with PTV was greater than the control flexion exercise (Fig. 8) the absolute muscle tension generated during flexion with PTV was greater than during flexion alone.

Figure 2.

The haemodynamic and effort sense responses to static exercise

Ratings of perceived exertion (RPE), heart rate (HR) and mean arterial pressure (MAP) responses at rest, recovery and during 3 min one-legged static knee extension (A-C) or flexion (D-F) (30 % maximal voluntary contraction (MVC)) without (•) and with (○) the application of vibration in 8 healthy subjects. Values are means ±s.e.m. * Indicates significantly different from control extension or flexion without vibration (P < 0.05).

Table 1. Oxygen uptake during 3 min of static exercise
  Rest VO2(l min−1)Exercise VO2 (l min−1)
  1. Values are means ±s.e.m.*Significantly different from rest; †significantly different from control exercise; ‡ significantly different from vibration exercise (P < 0.05).

I. Comparisonbetween control and vibration trials
 Knee extension30% MVC(n= 8)0.341 ± 0.0180.465 ± 0.014*
 30% MVC + vibration (n= 8)0.335 ± 0.0110.484 ± 0.038*
 Knee flexion30% MVC(n= 8)0.342 ± 0.0210.409 ± 0.030*
 30% MVC + vibration (n= 8)0.326 ± 0.0190.475 ± 0.046*†R
II. Comparison between workloads with and without vibration at the same RPE
 Knee extension30% MVC + vibration (n= 8)0.335 ± 0.0110.484 ± 0.038*
 22.6% MVC (n= 7)0.357 ± 0.0320.411 ± 0.026‡
 Knee flexion30% MVC + vibration (n= 8)0.326 ± 0.0190.475 ± 0.046*
 41.0% MVC(n= 7)0.370 ± 0.0240.465 ± 0.034*
Figure 8.

Electromyograph (EMG) signal from the quadriceps and the hamstrings muscles during flexion with (A) or without (B) the applied vibration at 30 % MVC for one subject.

CBR control of HR

The stimulus-response curves for the CBR control of HR are shown in Fig. 3A for static knee extension and Fig. 4A for static knee flexion modelled at rest, during the exercise with and without PTV. The data presented in Fig. 3A indicate that the application of PTV during the static extension exercise resets the CBR downward to a decreased operating carotid sinus pressure (OP). The data summarized in Fig. 4A indicate that the increases in central command evoked by the PTV reset the CBR upward to a higher OP.

Figure 3.

The effects of reduction of central command on carotid baroreflex (resetting)

Reflex responses in HR (A) and MAP (B) after rapid pulse train perturbation to the carotid sinus baroreceptors at rest (a); during control static knee extension (30 % MVC) one-legged exercise (c) and during static knee extension exercise with application of agonist patellar tendon vibration (b; dotted line). Lines represent mean fit of the individual subjects' data. Parameters calculated from logistic function curve model (Table 2) are as follows: prestimulus operating point (▵), centring point or point of maximal gain (▾), carotid sinus pressure threshold (•) and carotid sinus pressure saturation (○). Maximal gain and differences between at rest and during exercise in threshold pressure (dThr), saturation pressure (dSat), operating point (dHRop or dMAPop), centring point (dHRcp or dMAPcp) and different HR or MAP between OP and CP (CP – OP) are illustrated in the histogram summary of the data. Values are means ±s.e.m. * Significantly different from rest; # significantly different from control exercise (P < 0.05). Downward shift of stimulus-response curves is representative of central command effect on carotid baroreflex resetting during exercise. Maximal gain of reflex was not altered from resting control values during control or agonist patellar tendon vibration exercise.

Figure 4.

The effects of increase of central command on carotid baroreflex (resetting)

Reflex responses in HR (A) and MAP (B) after rapid pulse train perturbations to the carotid sinus baroreceptors at rest (a); during control static knee flexion (30 % MVC) one-legged exercise (b) and during static knee flexion exercise with application of antagonist patellar tendon vibration (c; dotted line). Lines represent mean fit of the individual subjects' data. Parameters calculated from the logistic function curve model (Table 2) are as follows: prestimulus operating point (▵) centring point or point of maximal gain (▾), carotid sinus pressure threshold (•), and carotid sinus pressure saturation (○). Maximal gain and differences between at rest and during exercise in threshold pressure (dThr), saturation pressure (dSat), operating point (dHRop or dMAPop), centring point (dHRcp or dMAPcp) and different HR or MAP between OP and CP (CP – OP) are illustrated in the histogram summary of the data. Values are means ±s.e.m. * Significantly different from rest; # significantly different from control flexion (P < 0.05). Maximal gain of reflex was not altered from resting control values during control or antagonist patellar tendon vibration exercise.

The reset of the CBR-HR function curve was confirmed by the fact that PTV, when applied during static extension and flexion exercise, resulted in significant changes in the carotid-cardiac baroreflex (CBR-HR) parameters. The four logistic parameters (A1-A4) for the carotid-cardiac baroreflex during static knee extension and flexion are presented in Table 2. The range of HR responses (A1) and the gain coefficient (A2) were unaltered between the control exercises and the exercises with PTV during both knee flexion and extension. However, when the exercise data were compared with the resting values, the carotid sinus pressure (CSP) at the centring point (CP), A3, was increased during both control knee extension and flexion. The A3 pressure of the CP was increased further from control exercise during knee flexion with PTV (P < 0.01), while during knee extension with PTV the A3 pressure of the CP was decreased from the control extension exercise (P < 0.01). Similarly, the minimal HR response (A4) was increased during both knee extension and flexion from rest (P < 0.05). During flexion the A4 or the minimal HR response was further augmented by application of PTV (P > 0.05), while the A4 value, (or the minimal HR response) during extension was significantly reduced by PTV.

Table 2. Logistic model parameter describing carotid sinus baroreceptor reflex control of HR and MAP (comparison between control and vibration trials)
 I. Carotid-cardiac baroreflex
  A 1, range(max-min)(beats min−1) A 2, gain coefficient A 3, carotid sinus pressure at midpoint ‡(mmHg) A 4, minimal response (beats min−1)
Rest (n= 8)15.7 ± 1.30.14 ± 0.0392.3 ± 4.752.5 ± 3.8
 Knee extension    
 30% MVC (n= 8)14.8 ± 2.40.16 ± 0.04129.4 ± 6.2*69.9 ± 3.8*
 30% MVC + vibration (n= 8)16.1 ± 2.70.13 ± 0.03109.8 ± 4.9*†63.8 ± 4.7*†
Knee flexion    
 30% MVC(n= 8)12.9 ± 2.10.22 ± 0.0693.2 ± 8.861.8 ± 4.6*
 30% MVC + vibration (n= 8)16.0 ± 2.80.17 ± 0.04112.6 ± 5.4*†64.4 ± 5.1*
 II. Carotid-vasomotorbaro reflex
  A 1, range (max-min)(mmHg) A 2, gain coefficient A 3, sinus pressureat midpoint ‡(mmHg) A 4, minimal response (mmHg)
  1. Values are means ±s.e.m.‡ Centring point. *Significantly different from resting; † significantly different from control exercise (P < 0.05).

Rest (n= 8)13.4 ± 1.30.12 ± 0.0496.8 ± 5.281.9 ± 3.0
Knee extension    
 30% MVC(n= 8)11.4 ± 1.50.15 ± 0.05132.3 ± 5.6*108.0 ± 4.1*
 30% MVC + vibration (n= 8)11.5 ± 1.30.18 ± 0.05110.5 ± 5.2†102.4 ± 4.1*
Knee flexion    
 30%MVC(n= 8)12.2 ± 2.00.10 ± 0.0298.3 ± 6.189.1 ± 5.3
 30% MVC + vibration (n= 8)14.3 ± 1.20.11 ± 0.02104.6 ± 8.299.1 ± 4.9*†

The stimulus-response variables that were calculated from the four logistic parameters for the carotid-cardiac baroreflex are presented in Fig. 3A and Fig. 4A. During extension and flexion control exercise, the carotid sinus pressure of threshold (CSPthr) and saturation (CSPsat) for the CSP-HR stimulus-response curves were reset to higher CSP values from those measured at rest. In addition, the CSPthr and CSPsat during static knee flexion were increased from control exercise with PTV. Conversely, these values during static knee extension were decreased from control exercise by PTV. The operating point (OP) and centring point (CP) of HR were relocated to a higher value than at rest during both static exercises (P < 0.05). In addition, both OP and CP were further relocated to a higher CSP (P < 0.05) during knee flexion and to a lower CSP (P < 0.05) during knee extension when the exercises were performed with PTV when compared to the control exercises. The relationship between the OP and CP for CSP-HR was unaltered by the knee flexion exercise performed with and without PTV (P > 0.05). However, it was observed that the PTV decreased the distance between OP and CP for CSP-HR during knee extension (Fig. 3A). The maximal gain (Gmax) of the HR response was similar between all experimental conditions.

CBR control of MAP

The stimulus-response curves for the CBR control of MAP are shown in Fig. 3B for static knee extension and Fig. 4B for static knee flexion, at rest, and exercise with and without the PTV. The carotid-MAP reflex curves were also reset upwards during flexion and downwards during extension by the application of PTV. The four logistic parameters (A1-A4) for the carotid-MAP baroreflex during static knee extension and flexion are presented in Table 2. The range of MAP responses (A1) and the gain coefficient (A2) were not different between rest and control exercises. Also, these values were not changed during either of the exercise conditions by the application of PTV. The CSP at the centring point (CP-A3) was increased from rest during both control knee extension and flexion exercise. A3 or the CP was non-significantly increased further from control exercise during knee flexion with PTV, while the A3 pressure or centring point (CP) pressure for the knee extension exercise with vibration was decreased significantly from the CP of the control extension exercise. Similarly, the minimal MAP response (A4) was increased during both knee extension and flexing from rest. Therefore, during flexion, the A4 pressure was augmented by PTV (P < 0.05) while during extension the A4 pressure was reduced by PTV (P > 0.05).

The stimulus-response variables that were calculated from the four logistic parameters for the carotid-MAP baroreflex are presented in Fig. 3B and Fig. 4B. The maximal gain (Gmax) and the CBR control of MAP were not different between either of the experimental conditions. There was an increase in the carotid sinus pressure of threshold (CSPthr) and saturation (CSPsat) for the CSP-MAP stimulus- response curve with static knee extension (P < 0.05) and flexion (P > 0.05) compared with rest. In addition, there were increases in the CSPthr and CSPsat pressures during static knee flexion with PTV. Conversely, the CSPthr and CSPsat during static knee extension were significantly decreased from control exercise by PTV. The operating point (OP) and centring point (CP) pressures were relocated to a higher pressure than at rest during static exercise (P < 0.05) and were increased from control exercise during knee flexion with PTV (P < 0.05). During knee extension with PTV the OP and CP of MAP was decreased from the control exercise (P < 0.05). The relationship between the OP and CP pressures for the CSP-MAP stimulus-response curve was unaltered by exercise with and without PTV during flexion (P > 0.05). However, it was observed that the PTV decreased the pressure between OP and CP for the CSP-MAP stimulus-response curve (P < 0.05) during knee extension (Fig. 3B).

Cardiovascular response to exercise at the same RPE with and without patellar tendon vibration (PTV)

Seven subjects performed static knee extension or flexion at the same amount of central command (RPE) as knee extension or flexion at 30 % MVC with the application of PTV. These amounts of effort sense (or central command) were confirmed by matching the RPE obtained during flexion or extension exercises with PTV. The HR responses to static knee extension or flexion at 30 % MVC with PTV were not different (P > 0.05) from the decreased or increased force produced without PTV but matched to the same RPE (Fig. 5). The MAP recorded during extension at the decreased force produced at the same RPE was lower than the MAP obtained during the 30 % MVC exercise with the PTV (P < 0.05). However, it was observed that the MAP response during knee flexion at the greater exercise intensity without PTV but at the same RPE as that obtained for the PTV trial at 30 % MVC was not different (P > 0.05). Because of low muscle work, the VO2 during knee extension at decreased workload was significantly lower than that during the PTV trial at 30 % MVC (Table 1). However, the VO2 during knee flexion at increased exercise intensity was not different from that during the PTV trial at 30 % MVC (Table 1).

Figure 5.

The haemodynamic responses to muscle tension performed at the same effort sense

Ratings of perceived exertion (RPE), heart rate (HR) and mean arterial pressure (MAP) responses at rest, recovery and during 3 min one-legged static knee extension (A-C) or flexion (D-F) at the decreased or increased intensity required to equalize RPE without vibration (○; 20 % or 40 % maximal voluntary contraction (MVC); n= 7) and with vibration (•; 30 % MVC; n= 8) in healthy subjects. Values are means ±s.e.m. *Significantly different from lower intensity extension without vibration (P < 0.05).

CBR control of HR at the same RPE with and without patellar tendon vibration (PTV)

The stimulus-response curves for the CBR control of HR are shown in Fig. 6A for static knee extension and Fig. 7A for static knee flexion; these figures summarize the data for the exercise with the PTV and the lower or higher exercise intensity at the same RPE during extension and flexion, respectively. Figure 6A and Figure 7A indicate that the CSP-HR stimulus-response curve was unaltered by the difference in exercise intensity during static exercise performed at the same RPE. The A1 and A2 of the HR responses were unaltered during knee extension or flexion with PTV during the decreased or increased exercise intensity conditions (Table 3) at the same RPE. The A3 and A4 of HR responses demonstrated progressive increases from rest during knee extension or flexion at both conditions. However, A3 and A4 of HR responses at 30 % MVC with PTV were the same as those obtained during flexion or extension performed at the same RPE.

Figure 6.

The effects of reduction of muscle tension performed at the same effort sense on carotid baroreflex resetting

Reflex responses in HR (A) and MAP (B) after rapid pulse train perturbations to the carotid sinus baroreceptors at rest (a); during static knee extension at 30 % MVC exercise with the application of agonist patellar tendon vibration (b); and during the decreased intensity (22.6 % MVC) extension without vibration (c; dotted line). Lines represent mean fit of individual subjects' data. Parameters calculated from logistic function curve model (Table 3) are as follows: prestimulus operating point (▵), centring point or point of maximal gain (▾), carotid sinus pressure threshold (•), and carotid sinus pressure saturation (○). Maximal gain and differences between at rest and during exercise in threshold pressure (dThr), saturation pressure (dSat), operating point (dHRop or dMAPop), centring point (dHRcp or dMAPcp) and different HR or MAP between OP and CP (CP – OP) are illustrated in the histogram summary of the data. Values are means ±s.e.m. * Significantly different from rest; # significantly different from the extension exercise with applied vibration (P < 0.05). Maximal gain of reflex was not altered from resting control values during agonist patellar tendon vibration or low intensity extension.

Figure 7.

The effects of increase of muscle tension performed at the same effort sense on carotid baroreflex resetting

Reflex responses in HR (A) and MAP (B) after rapid pulse train perturbations to the carotid sinus baroreceptors at rest (a); during static knee flexion exercise with application of antagonist patellar tendon vibration (b) and at greater intensity (41.0 % MVC) of flexion without vibration (c; dotted line). Lines represent mean fit of individual subjects' data. Parameters calculated from logistic function curve model (Table 3) are as follows: prestimulus operating point (▵), centring point or point of maximal gain (▾), carotid sinus pressure threshold (•), and carotid sinus pressure saturation (○). Maximal gain and differences between at rest and during exercise in threshold pressure (dThr), saturation pressure (dSat), operating point (dHRop or dMAPop), centring point (dHRcp or dMAPcp) and different HR or MAP between OP and CP (CP – OP) are illustrated in the histogram summary of the data. Values are means ±s.e.m. * Significantly different from rest (P < 0.05). Maximal gain of reflex was not altered from resting control values during antagonist patellar tendon vibration or high intensity flexion.

Table 3. Logistic model parameter describing carotid sinus baroreceptor reflex control of HR and MAP (the comparison between 30% MVC plus vibration and intensities only at equal RPE)
 I. Carotid-cardiac baro reflex
 RPE A 1, range (max-min) (beats min−1) A 2, gain coefficient A 3, carotid sinus pressure at midpoint ‡ (mmHg) A 4, minimal response (beats min−1)
Rest (n= 8) 15.7 ± 1.30.14 ± 0.0392.3 ± 4.752.5 ± 3.8
Knee extension     
 30% MVC + vibration(n= 8)12.416.1 ± 2.70.13 ± 0.03109.8 ± 4.9*63.8 ± 4.7*
 22.6% MVC (n= 7)12.618.4 ± 3.30.23 ± 0.06104.3 ± 3.362.1 ± 5.0*
Knee flexion     
 30% MVC + vibration(n= 8)13.416.0 ± 2.80.17 ± 0.04112.6 ± 5.4*64.4 ± 5.1*
 41.0% MVC(n= 7)13.714.4 ± 2.00.24 ± 0.11115.5 ± 4.7*62.3 ± 5.4*
 II. Carotid-vasomotor baroreflex
 RPE A 1, range (max – min) (mmHg) A 2, gain coefficient A 3, carotid sinus pressure at midpoint ‡ (mmHg) A 4 minimal response (mmHg)
  1. Values are means ±s.e.m.‡ Centring point. *Significantly different from resting; † significantly different from exercise with vibration (P < 0.05).

Rest (n= 8)13.4 ± 1.30.12 ± 0.0496.8 ± 5.281.9 ± 3.0 
Knee flexion     
 30% MVC + vibration (n= 8)12.411.5 ± 1.30.18 ± 0.05110.5 ± 5.2102.4 ± 4.1*
 22.6% MVC (n= 7)12.613.0 ± 2.70.16 ± 0.0495.9 ± 5.196.2 ± 3.5*†
Knee flexion     
 30% MVC + vibration (n= 8)13.414.3 ± 1.20.11 ± 0.02104.6 ± 8.299.1 ± 4.9*
 41.0% MVC (n= 7)13.711.7 ± 2.20.14 ± 0.02105.1 ± 5.9102.6 ± 3.5*

The stimulus-response variables that were calculated from the four logistic parameters for carotid-cardiac baroreflex obtained during knee flexion or extension exercise performed at the same RPE as obtained during the PTV experiments are presented in Fig. 6A and Fig. 7A. The parameters of CSPthr, CSPsat, OP and CP for the CSP-HR stimulus-response curves were unaltered by PTV and the lower or higher exercise intensity performed at the same RPE. In addition, the relationship between the OP and CP for the CSP-HR stimulus-response curve was unaltered by patellar tendon activation during both flexion and extension for exercise performed at the same RPE. Moreover, the maximal gain (Gmax) of the HR response was similar for all experimental conditions.

CBR control of MAP at the same RPE with and without patellar tendon vibration (PTV)

The stimulus-response curves for the CBR control of MAP are shown in Fig. 6B for static knee extension and Fig. 7B for static knee flexion, summarizing the data for the exercise with the PTV and the lower or higher exercise intensity at the same RPE during extension and flexion, respectively. The carotid-MAP reflex curves of the lower force produced at the same RPE as the 30 % MVC extension with PTV were relocated to a lower CSP. However, the CSP-MAP stimulus-response curve was similar during flexion exercises at the greater force produced at the same RPE observed during flexion with PTV.

The response range (A1) and the gain coefficient (A2) of the MAP responses were not different between the two conditions during knee extension or flexion when the exercises were performed at the same RPE (Table 3). In addition, the centring point (CP) A3 of MAP was unaltered by the decreased or incremental exercise intensity during extension or flexion, respectively, when the exercises were performed at the same RPE. However, the minimal response (A4) of MAP was unaltered by the increased exercise intensity but was significantly reduced from the A4 obtained in the PTV trial during extension performed at the same RPE (Table 3). The stimulus-response variables that were calculated from the four logistic parameters for the carotid-vasomotor baroreflex are presented in Fig. 6B and Fig. 7B. The Gmax of the CBR control of MAP was not different between all conditions during extension or flexion. There were reductions in CSPthr and CSPsat during knee extension at the decreased force exercise during the same RPE trial compared with the PTV trial, but these changes were not significant. In addition, the OP and the CP were decreased (P < 0.05) during knee extension at the decreased exercise intensity at the RPE of the vibration trial. However, during knee flexion these parameters (CSPthr, CSPsat, OP and CP) were unaltered when the increased exercise intensity was performed at the same RPE of the flexion plus PTV exercise. The relationship between the OP and CP for the CSP-MAP stimulus-response curve was unaltered by exercise at the lesser or greater exercise intensity during both exercises performed at the same RPE.

Discussion

The data of the present investigation independently verify previous reports in animals (McIlveen et al. 2001) and humans (Gallagher et al. 2001b) that central command actively contributes to carotid baroreflex resetting during exercise. By using the uniquely selective tendon vibration paradigm, we were able to demonstrate that the carotid baroreflex was further reset upwards on the response arm and rightwards to higher operating arterial pressures during knee flexion exercise with antagonist patellar tendon vibration (i.e. increased central command). In contrast, but of equal importance, the data obtained during knee extension exercise with agonist patellar tendon vibration (i.e. decreased central command) demonstrated that the carotid baroreflex was reset lower on the response arm and leftwards to lower operating arterial pressures. Further, this resetting occurred in the absence of the increased subject anxiety and/or nociceptive input often caused during neural blockade experiments.

In an effort to determine the selectivity of the tendon vibration technique in activating central command, seven of the subjects were asked to repeat the knee extension and knee flexion exercise at the same RPE. Williamson et al. (2001) have demonstrated that the individual's RPE or ‘effort sense’ during physical activity, independent of the force production, appears to dictate the magnitude of central command (Asmussen, 1965; Hobbs & Gandevia, 1985; Leonard et al. 1985; Gandevia & Hobbs, 1990). Hence, by comparing exercise with vibration to the exercise without vibration (Study 2, Fig. 1) at the same RPE (or effort sense) we expected to account for activation of the exercise pressor reflex (Potts & Mitchell, 1998; Gallagher et al. 2001a) in the resetting of the carotid baroreflex.

Although, the same amount of central command was reflected by there being no significant difference in RPE and HR between 30 % MVC with agonist vibration exercise and the smaller 22.6 % MVC force without vibration (Fig. 5), the MAP responses were decreased significantly during static knee extension with the smaller force development. Therefore, it was apparent that the smaller force effectively reduced the input of the exercise pressor reflex at the same amount of central command activation during knee extension. This reduction in exercise pressor reflex afferent input resulted in the carotid-HR response curves being unaltered by the decreased muscle tension when performed using the same amount of central command. However, the carotid-MAP reflex curves were reset downwards during decreased muscle contraction performed at the same central command. These data suggest a predominant effect of central command on the HR responses to exercise and its effect on the resetting of the carotid-HR baroreflex function curve. However, the data also suggest that the resetting of the carotid-vasomotor (CBR-MAP) baroreflex function curve was accomplished by a redundant activation of both central command and the exercise pressor reflex.

Conversely, during static knee flexion the subjects performed at a greater force (41.0 ± 2.4 % MVC) to achieve the same RPE as that obtained during the knee flexion exercise at 30 % MVC with vibration. Thus, the subjects required the same central effort with increased activation of the exercise pressor reflex to achieve the greater absolute force (41.0 % MVC) compared to the static knee flexion of 30 % MVC plus patellar tendon vibration. Surprisingly, the MAP responses were not increased significantly during static knee flexion at the 41.0 % MVC force compared with the 30 % MVC plus vibration flexion exercise. During knee flexion carotid-HR and carotid-MAP had the same responses during the 41.0 % MVC flexion exercise performed without vibration compared with the 30 % MVC flexion exercise performed with vibration (Fig. 7). We suggest that because the amplitude of the EMG in the hamstrings during flexion with the patellar tendon vibration was greater than the control flexion exercise in some subjects (Fig. 8), it was possible that the technique was unable to selectively isolate central command by utilizing the patellar tendon vibration technique during knee flexion. It was likely that the increased exercise pressor reflex activity of the 41.0 % MVC force without vibration (Fig. 1, Trial III) was not much different from the exercise pressor reflex activation that occurred during the 30 % MVC flexion plus patellar tendon vibration trial. In summary, the patellar tendon vibration technique appeared to jointly activate both the central command and the exercise pressor reflex in the control of the carotid-vasomotor (CBR-MAP) reflex and suggests that the resetting of the carotid-vasomotor reflex during exercise functions through both central command and the exercise pressor reflex. Because of technical difficulties in consistently maintaining the vibrator at the same position on the patellar tendon during dynamic exercise, we are currently unable to verify similar findings using this exercise modality. However, based upon the similarity of responses to both static and dynamic exercise obtained during muscle weakness experiments (Gallagher et al. 2001b) and activated exercise pressor reflex experiments (Gallagher et al. 2001a) we would expect similar findings to be obtained from patellar tendon vibration studies during dynamic exercise.

Previously, Strange et al. (1993) evaluated the role of central command and the exercise pressor reflex in the control of the cardiovascular response to exercise. In nine subjects exercise was performed under three conditions: (i) voluntarily; (ii) during electrically stimulated (E-S) muscle contraction (i.e. no central command); and (iii) during E-S muscle contraction with epidural anaesthesia (i.e. no central command and no exercise pressor reflex). During voluntary exercise, arterial blood pressure was increased. During E-S exercise, the increase in blood pressure was augmented. However, during E-S muscle contraction under epidural anaesthesia the increase in arterial blood pressure was abolished. In a separate study, Winchester et al. (2000) demonstrated the contribution of central command and the exercise pressor reflex to cardiovascular control during static exercise in patients with Brown-Sequard syndrome (i.e. spinal cord hemi-section). Their data indicated that the magnitude of the HR and blood pressure responses in these patients was affected by the level of central command activity. In addition, the cardiovascular response was determined to be mediated by the exercise pressor reflex in the absence of central command in these individuals. Importantly, these studies also suggested that activation of either central command or the exercise pressor reflex was requisite for the parallel resetting of the arterial baroreflex. These investigations along with the data of the present study provide evidence of the redundancy of the two major neural control mechanisms involved in the control of the cardiovascular system during exercise.

Although the relative intensity during knee extension was the same as for knee flexion (30 % MVC), the RPE, HR and MAP responses to knee extension were larger than during the knee flexion exercise (Fig. 2). Petrofsky et al. (1981) indicated the importance of muscle fibre composition in determining the blood pressure response for isometric contractions. In addition, Silva et al. (1999) found that the HR increase or EMG activity was significantly higher in isometric knee extension than flexion. Therefore, it is likely that the predominant mechanism responsible for the larger increase in these responses to knee extension as compared to flexion was dependent on qualitative and quantitative differences in the fibre type composition found in each muscle group.

The neural pathways involved in the activation of central command remain an area of intense investigation. Anatomical and physiological investigations in animals (Yasui et al. 1991; Waldrop et al. 1996) have identified the insular cortex and the locomotor regions of the hypothalamus and mesencephalon as potential sites for the generation of central command (Waldrop et al. 1996). In addition, the dorsolateral, ventrolateral, periventricular and commissural regions of the nucleus tractus solitarius have been identified as possible sites of integration of inputs from sites generating central command with the afferent input from the arterial baroreflexes and the exercise pressor reflex (Yasui et al. 1991; Potts & Mitchell, 1998). In humans, the use of Single Photon Emission Computerized Tomography (SPECT) or Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) for measures of the anatomical location of active metabolic brain activity used in conjunction with hypnotic manipulation of effort sense (Fink et al. 1995; Williamson et al. 2001) and imagined exercise (Thornton et al. 2001; Williamson et al. 2002) have anatomically identified sites where motor and cardiovascular activities vary in relation to perception of effort (Williamson et al. 2001, 2002). Most recently, Thornton et al. (Thornton et al. 2002) demonstrated that electrical stimulation of the thalamus and basal ganglia of the midbrain in humans evoked increases in heart rate and arterial blood pressure. These findings suggest that activation of the insular and cingulate cortices and the midbrain may play a major role in the central activation of the cardiovascular responses to exercise.

In conclusion, the present investigation supports the hypothesis that central command actively contributes to baroreflex resetting during static exercise. The data further suggest that central command plays a predominant role in the resetting of the carotid-cardiac reflex. In contrast, both central command and exercise pressor reflex activation are requisite for carotid-vasomotor resetting.

Acknowledgements

We appreciate the support provided by Scott Smith, PhD, University of Texas Southwestern Medical Center, Dallas, Texas, and the secretarial support in preparation of the manuscript by Lisa Marquez. We also sincerely thank the subjects for their interest and cooperation. This study was supported in part by the National Institutes of Health (NIH) Grant HL45547 and by the National Life Sciences Division of the National Aeronautics and Space Administration (NASA) of the United States under grant NAG5-4668.

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