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Journal of Physiology (2001), 533.3, pp. 861-870
© Copyright 2001 The Physiological Society
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ABSTRACT |
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INTRODUCTION |
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Concomitant increases in heart rate (HR) and mean arterial pressure (MAP) in response to physical activity have led investigators to conclude that the arterial baroreflex is either attenuated or not necessary during exercise (Bristow et al. 1971; McRitchie et al. 1976; Mancia et al. 1978). However, Melcher & Donald (1981) determined that during exercise the carotid baroreflex maintained its sensitivity. In addition, they suggested that the operating point of the baroreflex was relocated upward on the response arm of the baroreflex function curve in direct relation to the intensity of exercise. The relocation of the arterial baroreflex would enable a coincident increase in both HR and MAP. Subsequently, DiCarlo & Bishop (1992) demonstrated that the arterial baroreflex immediately resets at the start of exercise. Potts et al. (1993) have provided evidence that baroreflex function was maintained during exercise and was relocated upward on the response arm and rightward to higher operating pressures (classical resetting). Furthermore, this study described a relocation of the operating point away from the centring point and closer to the threshold pressure region of the baroreflex function curve. These data suggested that baroreflex function was reset to operate around the prevailing exercise-induced blood pressure. In addition, the relocation of the operating point allowed the baroreflex to respond to a wider range of carotid sinus hypertension. It has been confirmed that the resetting of the carotid baroreflex occurs in direct relation to the intensity of exercise (rest to maximum exercise) (Papelier et al. 1994; Norton et al. 1999) and that the resetting of the CBR occurs during static exercise (Ebert, 1986).
Rowell & O'Leary (1990) presented a hypothetical scheme suggesting that two neural mechanisms were primarily involved in the resetting of the carotid baroreflex during exercise. They proposed that a feed-forward neural mechanism (central command), which activates cardiovascular and motor responses in parallel, was responsible for relocating the operating point of the carotid baroreflex to higher arterial blood pressure (rightward) during exercise. This would allow for the reflex to remain operational despite the increased blood pressure that occurs with exercise. They also proposed that a negative feedback mechanism originating in the exercising muscle (exercise pressor reflex) was involved in the resetting of the baroreflex. It was suggested that the exercise pressor reflex would activate sympathetic neural activity resulting in a vertical relocation of the operating point of the arterial baroreflex. Together, these two neural mechanisms would result in the rightward and upward resetting of the baroreflex during exercise.
Goodwin et al. (1972) have provided evidence that cardiorespiratory control was altered in direct relation to changes in central command during exercise. Furthermore, the use of neuromuscular blockade to activate central command has demonstrated increases in HR, arterial blood pressure (Gandevia et al. 1993; Pawelczyk et al. 1997) and muscle sympathetic nerve activity (Victor et al. 1989). Norton et al. (1999) demonstrated that during prolonged steady-state exercise, carotid baroreflex resetting was directly related to development of muscle fatigue. They hypothesised that since central command was known to influence somatomotor responses, their findings provided evidence of its possible involvement in the resetting of the carotid baroreflex during exercise. Iellamo et al. (1997) have confirmed that in humans subjects central command and the exercise pressor reflex together were involved in the resetting of the arterial baroreflex during exercise. However, the influence of central command alone on the resetting of the carotid baroreflex has yet to be directly investigated.
This study attempted to increase central command influence on cardiovascular variables during steady-state dynamic exercise and static exercise with partial neuromuscular blockade without altering the magnitude of exercise pressor reflex input. The investigation was designed to determine the role of central command in the resetting of the carotid baroreflex during static and dynamic exercise in humans.
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METHODS |
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Subjects
Eleven men and two women, with a mean age of 27.1 ± 1.1 years (± S.E.M.), height of 180.9 ± 1.9 cm, weight of 74.4 ± 1.7 kg and maximum oxygen uptake (
O2,max) of 3.49 ± 0.2 l min-1, volunteered to participate in this investigation. Each subject was informed of all aspects of the study and signed an informed consent approved by the Municipal Ethical Committee of Copenhagen, Denmark. All experiments were performed in accordance with the Declaration of Helsinki. All subjects were non-smokers, were not taking medication and were asymptomatic for cardiovascular and respiratory disease. The subjects were asked to abstain from alcoholic beverages and exercise for 24 h and caffeinated beverages for 12 h prior to any session.
Exercise
Each subject performed preliminary incremental work rate (30 W min-1) exercise on a cycle ergometer (modified Krogh) to volitional fatigue for the determination of O2,max. After the maximal exercise test, the subject was familiarised with the protocols for baroreflex testing and static exercise. On a separate day, the subjects performed static and dynamic exercise with and without the administration of whole-body curare (Norcuron; Organon Telemika). For both protocols the subjects were seated in a semi-recumbent position on a hospital bed which supported the subjects' upper body. The bed was modified to allow the subjects to perform one-legged static knee extension from a 90 deg knee angle and two-legged cycling. Preceding any exercise, the subjects attempted three static knee extensions to determine maximal voluntary contraction (MVC). Two bouts of control static knee extension at 20 % of MVC were performed for 3.5 min. The static exercise bouts were followed by a 7 min dynamic exercise protocol at 20 % O2,max. All exercise bouts were separated by a minimum of 30 min. After a minimum of 1 h the static and dynamic exercise bouts were repeated at the same absolute (20 % of control MVC and O2,max) workloads after the whole-body administration of Norcuron. Each exercise bout was preceded by a 5 min collection period for resting baseline measurements.
Static knee extension was accomplished by placing a padded strap around the ankle of the subject's dominant leg. Force was recorded by a strain gauge dynamometer calibrated prior to each trial with an accurate sensitivity (model 540 DNH, The Netherlands). In order for the subject to maintain the desired force, visual feedback of force produced was provided to the subject on a monitor. However, due to the effect of Norcuron on vision, verbal feedback was also used to maintain force during exercise following the administration of curare. For dynamic exercise, the cycle ergometer was adjusted for each subject so that the knee angle at maximal leg extension was consistent for both tests. Subjects were requested to maintain a pedal cadence of 60 r.p.m. as dictated by a metronome and they were instructed to keep their entire upper body relaxed during all testing.
Norcuron (10 mg (10 ml)-1), a non-depolarizing neuromuscular blocking agent, was administered through venous access in the back of the hand. Prior to Norcuron administration, static handgrip MVC was determined in arbitrary units. A bolus dose of Norcuron was injected followed by 10 ml of saline. Supplemental doses were administered until handgrip strength was reduced to 50 % of control. After the desired reduction in strength was achieved, the 5 min rest collection period was initiated followed by the exercise bout. The injections were repeated as required in order to maintain the targeted reduction in muscle strength. At all times an Ambu-E resuscitator apparatus, neostigmine and atropine were available.
Measurements
Heart rate was monitored by a standard lead II electrocardiogram. Mean arterial pressure (MAP) was monitored by a Teflon catheter (20 gauge) placed in the brachial artery of the non-dominant arm. The MAP catheter was connected to a sterile disposable pressure transducer (Baxter, Uden, The Netherlands) interfaced with a pressure monitor (Danico Electronic-Dialogue 2000, Denmark). The zero reference pressure was set at heart level. During each experiment the HR and arterial blood pressure (ABP; i.e. mean (MAP), systolic (SBP) and diastolic (DBP) blood pressures) were acquired using a beat-to-beat customized software data acquisition system interfaced with a personnel computer. In addition, ratings of perceived exertion (RPE) were obtained during the last 30 s of static exercise and at the 4th and 7th minute of dynamic exercise using the 6-20 Borg scale (Borg, 1982).
The subjects respired through a mouthpiece attached to a low-resistance turbine volume transducer (Pneumotach, MedGraphic) for measurements of breath volumes, while gases were continuously sampled from the mouthpiece for analysis of fractional concentrations of O2, CO2 and N2 to determine O2 uptake (mass spectrometer model 2001; Medical Graphics Corporation, St Paul, MN, USA). The system was calibrated before each test using known high-precision standard gases. 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.
Samples of arterial blood were obtained at rest and during the last 30 s of exercise for determination of plasma catecholamines and lactate concentration. Blood was placed in tubes kept on ice containing reduced glutathione and EGTA and centrifuged at 3000 g for 5 min at 3 °C. The plasma fraction was stored at -20 °C for blind analysis of noradrenaline (NA) and adrenaline (A). Samples were assayed by a single isotope radioenzymatic method (Knigge et al. 1990). Remaining syringe blood samples were used immediately for lactate determination (Lac TSI 2300; Yellow Springs Instrument Co., Inc., OH, USA).
Carotid baroreflex (CBR) control of HR and MAP was assessed using a neck pressure/neck suction (NP/NS) technique. Pressure stimuli were applied through a cushioned malleable collar placed around the anterior 2/3 of the neck. The neck collar was modified from a design described by Sprenkle et al. (1986). Due to the brevity of the exercise protocols, a NP/NS technique with a rapid ramping of pressure was used. Twelve computer controlled pulsatile pressures ranging from +40 to -80 mmHg (40, 40, 40, 40, 20, 10, 0, -10, -20, -40, -60, -80) were generated by a variable pressure source and delivered to the neck collar through large bore two-way solenoid valves (model 8215B, Asco, Florham Park, NJ, USA). Between each pressure pulse the neck chamber pressure was vented to atmospheric pressure. The generated neck collar pressure was measured by a pressure transducer (model DP45, Validyne Engineering, Northridge, CA, USA). The computer software gated the pressure pulses to occur 50 ms after initiation of the R-wave detected by ECG. The 50 ms delay allowed the artificial pressure/suction to coincide with the arterial pressure wave at the carotid sinus. Each pulse was 500 ms in duration. The NP/NS pulse train was conducted at end-expiratory breath hold to eliminate the confounding effects of respiratory sinus arrhythmia. The total duration of breath hold varied between 10 and 12 s. Six subjects were unable to maintain the end-expiratory breath hold throughout the entire NP/NS pulse train during dynamic exercise. Therefore only seven subjects were included in the dynamic exercise data. During static exercise, two trains of pressure pulses were applied after the second minute of exercise. Three to four trains of pressure pulses were applied during dynamic exercise after the 4th minute of exercise. A minimum of 45 s of recovery was allotted between rapid pulse trains of NP/NS. Pulse trains of NP/NS were also performed at rest before all exercise bouts.
Data and statistical analysis
The dependent variables HR and MAP were used to create either the carotid-cardiac (CSP-HR) or carotid-vasomotor (CSP-MAP) stimulus-response function curves when plotted against the independent variable of estimated carotid sinus pressure (CSP). These curves were individually fitted for each subject to a four parameter logistic function described by Kent et al. (1972). This function incorporates the following equation:
HR or MAP = A1{1 + exp[A2(CSP - A3)]}-1 + A4.
Carotid sinus pressure was calculated by subtracting the chamber pressure from the pre-stimulus MAP. Parameter A1 was the range of response of the dependent variable (maximum-minimum), A2 was the gain coefficient, A3 was the CSP required to elicit equal pressor and depressor responses (centring point) and A4 was the minimum response of HR or MAP. Individual data were applied to this model by a non-linear least-squares regression that predicts a curve of 'best fit' for the data and minimizes the sum of squares error.
Several characteristic parameters are derived from the resulting model including the estimated threshold (CSPthr), saturation (CSPsat) and maximal gain (Gmax) of the CSP-HR and CSP-MAP reflexes. Baroreceptor CSPthr and CSPsat were described as the minimum and maximum CSPs, respectively, that elicited a reflex change in HR or MAP. 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. They determined that these calculations of CSPthr and CSPsat represent the CSP at which MAP or HR were within 5 % of their maximal or minimal responses. The gains of the CSP-HR and CSP-MAP reflexes were derived from the first derivative of the Kent logistic function, with the maximal gain being defined as the gain value located at the centring point (CP) of the reflex. In addition, the operating point (OP) was defined as the intersection of the pre-stimulus HR or MAP and CSP (i.e. resting MAP). Centring point minus the operating point (CP - OP) was used to define the relocation of the OP away from the CP. Parameters for all subjects within an experimental condition were averaged to provide group mean responses.
A two-way analysis of variance (ANOVA) with repeated measures was employed to determine significant differences at rest and exercise between either static or dynamic exercise with or without curare. Student-Newman-Keuls post hoc pairwise comparisons were used to establish significant group mean differences. In addition, Student's paired t test was used for individual comparisons. Data are presented as mean values with standard errors (mean ± S.E.M.). Significance was set at P < 0.05. All analyses were conducted using SigmaStat (Jandell Corp.).
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RESULTS |
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Selected physiological responses
Partial neuromuscular blockade with curare (Norcuron) reduced static handgrip strength 50-60 % during rest, static and dynamic exercise (Table 1). The subjects reported that after partial neuromuscular blockade, increased effort was required to maintain the same absolute workload as control. This was reflected by significantly increased ratings of perceived exertion (RPE) during static and dynamic curare exercise as compared to the control exercise condition (Table 1). In addition, HR and MAP were significantly elevated by curare during static and dynamic exercise (Fig. 1 and Fig. 2). The HR and MAP reached steady state without additional elevations at the second minute of static exercise and at the fourth minute of dynamic exercise during control and neuromuscular blockade. Plasma arterial noradrenaline and lactate concentrations were significantly increased during static and dynamic exercise with curare compared with control (Table 1). Heart rate, MAP, noradrenaline and lactate were unaffected by curare at rest. At the same absolute work rate, oxygen uptake and plasma adrenaline concentration were unaltered by curare at rest and throughout exercise (Table 1).
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Figure 1. HR and MAP during 3 min of static exercise Heart rate and mean arterial pressure responses at rest and during 3 min one-legged static exercise (20 % maximal voluntary contraction) with ( | ||
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Figure 2. HR and MAP during 7 min of dynamic exercise Heart rate and mean arterial pressure responses at rest and during 7 min dynamic cycling exercise (20 % maximum oxygen uptake) with ( | ||
Logistic parameters of carotid baroreflex
The stimulus-response relationships for baroreflex control of HR (CSP-HR) and MAP (CSP-MAP) at rest and during static and dynamic exercise are shown in Fig. 3 and Fig. 4. The four logistic parameters describing carotid baroreflex control of HR and MAP during static and dynamic exercise are presented in Table 2. The centring point of the reflex (A3) was progressively relocated from rest during control exercise and was significantly increased from rest and control exercise during partial neuromuscular blockade. The minimal HR and MAP response (A4) was significantly increased during control exercise and was further augmented by the administration of curare. The range of HR and MAP responses (A1) and the gain coefficient (A2) were unaltered by exercise under control conditions and following administration of curare.
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Figure 3. Reflex responses in HR and MAP during static exercise Reflex responses in HR (carotid-cardiac) and MAP (carotid-vasomotor) after perturbations to carotid sinus baroreceptors at rest ( | ||
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Figure 4. Reflex responses in HR and MAP during dynamic exercise Reflex responses in HR (carotid-cardiac) and MAP (carotid-vasomotor) after perturbations to carotid sinus baroreceptors at rest ( | ||
Carotid baroreflex variables during static exercise
The calculated variables describing the CSP-HR and CSP-MAP stimulus-response curves during static exercise are shown in Tables 3 and 4. The maximal gains of the HR and MAP responses were found to be unaltered from that of rest by static exercise under control conditions and following administration of curare. Threshold (CSPthr) and saturation (CSPsat) carotid sinus pressures for CSP-HR and CSP-MAP responses were relocated to higher CSPs from that measured at rest during control static exercise and were significantly increased from control exercise by partial neuromuscular blockade. The difference between CSPthr and CSPsat measured under control conditions and following administration of curare was only significant using an a priori paired t test. The pre-stimulus (PS) HR and MAP were significantly increased from rest by control static exercise and were further significantly augmented by partial neuromuscular blockade. The relationship between the operating point (pre-stimulus CSP) and the centring point (A3) was not altered by control static exercise, but exercise following administration of curare increased the distance between the operating point and the centring point for CSP-HR, moving the operating point closer to the threshold of the reflex. The relationship between the operating point and the centring point for CSP-MAP was unaltered by exercise both under control conditions and following administration of curare. Collectively, the relocation upward on the response arm and rightward to higher operating pressures of the CSP-HR and CSP-MAP stimulus-response curves suggested resetting of the CBR during control exercise which was further augmented by partial neuromuscular blockade or an increased central command influence (Fig. 3).
Carotid baroreflex variables during dynamic exercise
The maximal gains of the HR and MAP responses were unaltered by dynamic exercise under control conditions and following administration of curare (Tables 3 and 4). Threshold (CSPthr) and saturation (CSPsat) carotid sinus pressures for CSP-HR and CSP-MAP responses were relocated to higher carotid sinus pressures from that measured at rest during control dynamic exercise and were significantly increased from control exercise pressures by partial neuromuscular blockade. Pre-stimulus HR was significantly increased from rest by control dynamic exercise. The operating point (pre-stimulus CSP) of CSP-HR was significantly shifted away from the centring point (A3) of the reflex, moving closer to threshold during control exercise; partial neuromuscular blockade had no additional effect. Pre-stimulus MAP was not altered by control exercise, but was significantly elevated from control exercise by partial neuromuscular blockade. In addition, the relationship between the operating point and the centring point for MAP was not altered by control dynamic exercise, but exercise following administration of curare significantly relocated the operating point away from the centring point, closer to the threshold of the reflex when compared to control. Collectively, the relocation upward on the response arm and rightward to higher operating pressures of the stimulus-response curves for CSP-HR and CSP-MAP suggest resetting of the CBR during control exercise which was augmented by partial neuromuscular blockade or when central command was increased (Fig. 4).
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DISCUSSION |
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The carotid baroreflex resets during dynamic and static exercise without alterations in sensitivity or maximal gain (Melcher & Donald, 1981; Ebert, 1986; DiCarlo & Bishop, 1992; Potts et al. 1993). In addition, the carotid baroreflex continuously resets in direct relationship to the intensity of exercise (Papelier et al. 1994; Norton et al. 1999). Rowell & O'Leary (1990) hypothesized that afferent neural signals from the exercise pressor reflex and efferent signals from central command combine to produce carotid baroreflex resetting during exercise. The present investigation was designed to selectively increase central command in order to determine its role in the resetting of the carotid baroreflex during dynamic and static exercise. We confirmed that the carotid baroreflex was reset during both static and dynamic exercise. The major new finding from this study was that the carotid baroreflex was further reset upward on the response arm and rightward to higher operating pressures from control exercise when central command was enhanced without alterations in gain. This response suggests that central command actively contributes to the resetting of the carotid baroreflex at the onset of static and dynamic exercise.
The cardiovascular responses to exercise are mediated in part by central command input (Goodwin et al. 1972; Innes et al. 1992). Central command is a 'feed-forward' controller that when activated has a diffuse outflow of efferent communication from its putative location in the hypothalamic locomotor region. Central command activates multiple centres involved in the initiation of motor activity (Waldrop et al. 1996) and is capable of initiating locomotion when stimulated (Waller, 1940). Additionally, locomotor region activation stimulates cardiovascular control centres in the ventrolateral medulla and lateral reticular nucleus of the medulla (Nolan et al. 1992). Thus it is thought that central command involves a parallel, simultaneous excitation of neuronal circuits that elicits motor unit recruitment and adjusts cardiovascular activity in a manner appropriate for the work (exercise) being performed (Waldrop et al. 1996). One model for independently studying central command has utilized partial neuromuscular blockade (Leonard et al. 1985; Galbo et al. 1987; Victor et al. 1989, 1995; Pawelczyk et al. 1997). Subjects exercising during partial neuromuscular blockade require increased motor unit recruitment to maintain the same absolute work rates as during control exercise. Therefore, since central command contributes to motor unit recruitment, partial neuromuscular blockade was hypothesized to augment central command (Mitchell, 1990).
We used whole-body curare (Norcuron) to partially block the neuromuscular junction during exercise in order to increase central command input. Each subject's handgrip strength was reduced to 40-50 % of their control MVC during partial neuromuscular blockade. Therefore, subjects required an increase in effort, i.e. central command, in order to maintain the same absolute work rates as during control exercise. This augmentation of central command was reflected by increased ratings of perceived exertion (RPE) during partial neuromuscular blockade. In addition, complementing previous work (Leonard et al. 1985; Pawelczyk et al. 1997), HR and MAP responses were augmented during partial neuromuscular blockade. Interestingly, oxygen uptake appeared to be unaffected by partial neuromuscular blockade. Despite the increased central effort needed to execute the work, the subjects were still performing the same absolute amount of work. In other words, increased central command activated additional motor units, but due to the neuromuscular blockade, the same amount of muscle fibres were required to achieve the same absolute work rate. Therefore, it is apparent that, due to its effects on HR and RPE, partial neuromuscular blockade effectively augmented central command without increasing the work of the active muscle, thereby maintaining the exercise pressor reflex input constant between conditions.
A unique finding of the present investigation was that partial neuromuscular blockade significantly increased blood lactate concentration above control exercise during both dynamic and static exercise protocols. Curare selectively inhibits slow-twitch muscle fibres resulting in a predominance of fast-twitch fibres remaining to perform work (Galbo et al. 1987). Activation of primarily fast-twitch muscle fibres would result in an augmentation of glycolytic production of lactate. It is also possible that activation of the sympathetic nervous system by central command may have stimulated the glycolytic pathway. However, the elevation of lactate values does raise the possibility of activation of the exercise pressor reflex via stimulation of chemically sensitive metaboreceptors.
Activation of proposed locations for central command originating in the motor cortex, insular cortex and the posterior hypothalamus (Bauer et al. 1988; Dillon et al. 1991; Waldrop et al. 1996; Saleh & Connell, 1998) have demonstrated alterations in baroreflex control of HR. In addition, medullary neurons that form the central baroreceptor pathway receive synaptic input from central command (McMahon et al. 1992; Waldrop et al. 1996; Potts et al. 1998). Thus, central command input may actively reset the carotid baroreflex by modulating medullary neuron pools that form the central baroreceptor pathway. During dynamic and static exercise in the present investigation, threshold and saturation carotid sinus pressures and the minimal response for the carotid-cardiac and carotid-vasomotor baroreflex curves were increased from rest during control exercise and were significantly elevated from control exercise by partial neuromuscular blockade. In addition, the centring point of the responses (A3) was significantly raised by control exercise and further significantly increased during neuromuscular blockade. The maximal gains of the HR and MAP responses were found to be unaltered by either control or neuromuscular blockade exercise. These responses coincide with Heesch & Carey's (1987) description of resetting of the carotid baroreflex as parallel increases in saturation and threshold without alterations in gain. Therefore, the carotid-cardiac and carotid- vasomotor stimulus- response curves were reset by control dynamic and static exercise and this resetting was further augmented upward on the response arm and rightward to higher operating pressures by neuromuscular blockade. The data of the present investigation suggest that central command was actively involved in the classic upward and rightward resetting of the carotid baroreflex during both dynamic and static exercise.
Potts et al. (1993) and Norton et al. (1999) report that steady-state HR and MAP (or CSP operating point) are relocated away from the centring point and progressively closer to the threshold region of the stimulus-response curve with each increment in dynamic exercise intensity. These findings suggest that a relocation of the operating point permits the carotid baroreflex to respond to a wider range of carotid sinus hypertension. We did not demonstrate any shifts in the location of the operating point on the baroreflex stimulus-response curves during static and dynamic exercise, except for the HR response to dynamic exercise. This was possibly due to the low dynamic and static work rates used in the present experiment. However, relocation of the pre-stimulus HR and MAP away from the centring point and closer to the threshold did occur during dynamic exercise following neuromuscular blockade. Therefore, central command appears to contribute to the relocation of the operating point during exercise, as previously suggested (Potts et al. 1993; Norton et al. 1999). This relocation may enable the carotid baroreflex to respond to systemic hypertension during exercise with a greater range of responses, a concept demonstrated by Sheriff et al. (1987) to provide a functional brake on the exercise pressor reflex.
The findings of the present investigation by no means exclude the involvement of the exercise pressor reflex in the resetting of the carotid baroreflex during exercise. McWilliam et al. (1991) have clearly demonstrated in animal studies that peripheral reflex mechanisms contribute to changes in the baroreceptor reflex during muscle contraction. The redundant nature of central command input and the exercise pressor reflex in the regulation of the cardiovascular system is generally accepted (Mitchell, 1990). In addition, several studies have provided evidence of vertical resetting of the carotid baroreflex during exercise pressor reflex stimulation (Eiken et al. 1992; Shi et al. 1993, 1997; Papelier et al. 1997). Potts & Mitchell (1998) have demonstrated rightward relocation of threshold CSP with activation of skeletal muscle afferents. Furthermore, medullary neurons that form the central baroreceptor pathway receive synaptic input from skeletal muscle receptors (Kalia et al. 1981; Nyberg & Blomqvist, 1984; Waldrop et al. 1996). Thus, it appears that the exercise pressor reflex is involved in the resetting of the carotid baroreflex. Given the findings of the present study, we suggest that central command (a feed-forward mechanism) is the primary mediator of carotid baroreflex resetting at the onset and during exercise. Further, the magnitude of resetting may be modulated by exercise pressor reflex input (a feedback mechanism) in response to mechanical and metabolic demands placed on active muscle.
In summary, we have confirmed that the stimulus- response relationship of the carotid baroreflex is reset during dynamic and static exercise to the prevailing systemic pressure. We also demonstrated that increased central command further resets the carotid baroreflex upward on the response arm and rightward to higher operating pressures (classical resetting) in the same manner during dynamic and static exercise without altering the gain of the reflex. In addition, we found that increased central command relocated the pre-stimulus HR and MAP, i.e. the operating point, away from the centring point and closer to the threshold of the reflex during exercise. We conclude that central command is actively involved in the 'classical resetting' of the carotid baroreflex that occurs between rest and the onset of exercise. Furthermore, the degree of resetting of the baroreflex is directly related to the intensity of the exercise which is commensurate with the magnitude of central command activation.
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Acknowledgements
The authors would like to thank Kasper Horn for his technical support and Lisa Marquez for secretarial support during the preparation of the manuscript. This study was supported by the Danish National Research Foundation Grant (504-14) from the Copenhagen Muscle Research Center, Copenhagen, Denmark. This paper was submitted by K. M. Gallagher to the University of North Texas Health Science Center at Fort Worth in partial fulfillment of the requirements for the degree of Doctor of Philosophy.
Corresponding author
P. B. Raven: Department of Integrative Physiology, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX 76107-2699, USA.
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) and without (
) administration of curare (partial neuromuscular blockade). Values are means ± S.E.M. * Significant difference between control and partial neuromuscular blockade exercise (P < 0.05).
) and during static exercise after administration of curare (Norcuron) for partial neuromuscular blockade (
). Data points represent means ± S.E.M. Lines represent mean fits of data from individual subjects. Arrows indicate operating points. Curare-rest curves were not significantly different from control-rest curves and have been omitted for clarity.