Central command blunts the baroreflex bradycardia to aortic nerve stimulation at the onset of voluntary static exercise in cats

To examine whether the central characteristics of the aortic baroreflex alter from moment to moment during static exercise, we identified the dynamic changes in the sizes of the bradycardia and depressor response evoked by stimulation of the aortic depressor nerve (ADN). Three conscious cats were trained to voluntarily extend the right forelimb and press a bar for 31 +/- 1 s with a peak force of 337 +/- 22 g while maintaining a sitting posture. The ADN stimulation-induced bradycardia was attenuated at the initial period of exercise (up to 8 s from the exercise onset) to 62 +/- 5% of the preexercise bradycardia and remained blunted until the end of exercise. The most blunted bradycardia was observed immediately before or when the forelimb was extended before force development. The baroreflex-induced bradycardia was suppressed again at cessation of exercise when the forelimb was retracted and recovered within a few seconds. In contrast, static exercise did not affect the ADN stimulation-induced depressor response. The ADN stimulation-induced bradycardia was also blunted at the beginning of naturally occurring body movement such as spontaneous postural change or grooming behavior. Thus it is likely that the central characteristics of the aortic baroreflex dynamically change from moment to moment during voluntary static exercise and during natural body movement and that particularly a central inhibition of the cardiac component of the aortic baroreflex is induced by central command at the onset of static exercise, whereas the central property of the vasomotor component of the baroreflex is preserved.     

Gadolinium does not blunt the cardiovascular responses at the onset of voluntary static exercise in cats: a predominant role of central command

The cardiovascular adaptation at the onset of voluntary static exercise is controlled by the autonomic nervous system. Two neural mechanisms are responsible for the cardiovascular adaptation: one is central command descending from higher brain centers, and the other is a muscle mechanosensitive reflex from activation of mechanoreceptors in the contracting muscles. To examine which mechanism played a major role in producing the initial cardiovascular adaptation during static exercise, we studied the effect of intravenous administration of gadolinium (55 micromol/kg), a blocker of stretch-activated ion channels, on the increases in heart rate (HR) and mean arterial blood pressure (MAP) at the onset of voluntary static exercise (pressing a bar with a forelimb) in conscious cats. HR increased by 31 +/- 5 beats/min and MAP increased by 15 +/- 1 mmHg at the onset of voluntary static exercise. Gadolinium affected neither the baseline values nor the initial increases of HR and MAP at the onset of exercise, although the peak force applied to the bar tended to decrease to 65% of the control value before gadolinium. Furthermore, we examined the effect of gadolinium on the reflex responses in HR and MAP (18 +/- 7 beats/min and 30 +/- 6 mmHg, respectively) during passive mechanical stretch of a forelimb or hindlimb in anesthetized cats. Gadolinium significantly blunted the passive stretch-induced increases in HR and MAP, suggesting that gadolinium blocks the stretch-activated ion channels and thereby attenuates the reflex cardiovascular responses to passive mechanical stretch of a limb. We conclude that the initial cardiovascular adaptation at the onset of voluntary static exercise is predominantly induced by feedforward control of central command descending from higher brain centers but not by a muscle mechanoreflex.     

Differential effect of central command on aortic and carotid sinus baroreceptor-heart rate reflexes at the onset of spontaneous, fictive motor activity

Our laboratory has reported that central command blunts the sensitivity of the aortic baroreceptor-heart rate (HR) reflex at the onset of voluntary static exercise in conscious cats and spontaneous contraction in decerebrate cats. The purpose of this study was to examine whether central command attenuates the sensitivity of the carotid sinus baroreceptor-HR reflex at the onset of spontaneous, fictive motor activity in paralyzed, decerebrate cats. We confirmed that aortic nerve (AN)-stimulation-induced bradycardia was markedly blunted to 26 ± 4.4% of the control (21 ± 1.3 beats/min) at the onset of spontaneous motor activity. Although the baroreflex bradycardia by electrical stimulation of the carotid sinus nerve (CSN) was suppressed (P < 0.05) to 86 ± 5.6% of the control (38 ± 1.2 beats/min), the inhibitory effect of spontaneous motor activity was much weaker (P < 0.05) with CSN stimulation than with AN stimulation. The baroreflex bradycardia elicited by brief occlusion of the abdominal aorta was blunted to 36% of the control (36 ± 1.6 beats/min) during spontaneous motor activity, suggesting that central command is able to inhibit the cardiomotor sensitivity of arterial baroreflexes as the net effect. Mechanical stretch of the triceps surae muscle never affected the baroreflex bradycardia elicited by AN or CSN stimulation and by aortic occlusion, suggesting that muscle mechanoreflex did not modify the cardiomotor sensitivity of aortic and carotid sinus baroreflex. Since the inhibitory effect of central command on the carotid baroreflex pathway, associated with spontaneous motor activity, was much weaker compared with the aortic baroreflex pathway, it is concluded that central command does not force a generalized modulation on the whole pathways of arterial baroreflexes but provides selective inhibition for the cardiomotor component of the aortic baroreflex.     

Central inhibition of the aortic baroreceptors-heart rate reflex at the onset of spontaneous muscle contraction.

Animals decerebrated at the precollicular-premammillary body level exhibit spontaneous locomotion without any artificial stimulation. Our laboratory reported that the cardiovascular and autonomic responses at the onset of spontaneous locomotor events are evoked by central command, generated from the caudal diencephalon and the brain stem (Matsukawa K, Murata J, and Wada T. Am J Physiol Heart Circ Physiol 275: H1115-H1121, 1998). In this study, we examined whether central command and/or a reflex resulting from muscle afferents modulates arterial baroreflex function using a decerebrate cat model. The baroreflex was evoked by stimulating the aortic depressor nerve (ADN) at the onset of spontaneous muscle contraction (to test the possible influence of central command) and during electrically evoked contraction or passive stretch (to test the possible influence of the muscle reflex). When the ADN was stimulated at rest, heart rate and arterial blood pressure decreased by 40 +/- 2 beats/min and 11 +/- 1 mmHg, respectively. The baroreflex bradycardia was attenuated to 55 +/- 4% at the onset of spontaneous contraction. The attenuating effect on the baroreflex bradycardia was not observed at the onset and middle of electrically evoked contraction or passive stretch. The depressor response to ADN stimulation was identical among resting and any muscle interventions. The inhibition of the baroreflex bradycardia during spontaneous contraction was seen after beta-adrenergic blockade but abolished by muscarinic blockade, suggesting that the bradycardia is mainly evoked through cardiac vagal outflow. We conclude that central command, produced within the caudal diencephalon and the brain stem, selectively inhibits the cardiac component, but not the vasomotor component, of the aortic baroreflex at the onset of spontaneous exercise.     

Sympathetic cholinergic nerve contributes to increased muscle blood flow at the onset of voluntary static exercise in conscious cats

We examined whether a sympathetic cholinergic mechanism contributed to increased blood flow of the exercising muscle at the onset of voluntary static exercise in conscious cats. After six cats were operantly conditioned to perform static bar press exercise with a forelimb while maintaining a sitting posture, a Transonic or pulsed Doppler flow probe was implanted on the brachial artery of the exercising forelimb, and catheters were inserted into the left carotid artery and jugular vein. After the baseline brachial blood flow and vascular conductance decreased and became stable in progress of postoperative recovery, the static exercise experiments were started. Brachial blood flow and vascular conductance began to increase simultaneously with the onset of exercise. Their initial increases reached 52 +/- 8% and 40 +/- 6% at 3 s from the exercise onset, respectively. Both a sympathetic ganglionic blocker (hexamethonium bromide) and atropine sulfate or methyl nitrate blunted the increase in brachial vascular conductance at the onset of static exercise, whereas an inhibitor of nitric oxide synthesis (N(omega)-nitro-l-arginine methyl ester) did not alter the increase in brachial vascular resistance. Brachial blood flow and vascular conductance increased during natural grooming behavior with the forelimb in which the flow probe was implanted, whereas they decreased during grooming with the opposite forelimb and during eating behavior. Thus it is likely that the sympathetic cholinergic mechanism is capable of evoking muscle vasodilatation at the onset of voluntary static exercise in conscious cats.     

Central neural correlates of learned heart rate control during exercise: central command demystified

Chefer, Svetlana I., Mark I. Talan, and Bernard T. Engel.Central neural correlates of learned heart rate control during exercise: central command demystified. J. Appl.Physiol. 83(5): 1448-1453, 1997.To identify thebrain areas involved in central command, four monkeys were trained toattenuate the tachycardia of exercise while different brain sitesaffecting heart rate (HR) were simultaneously stimulated electrically.Among 24 brain sites located mostly in the limbic structures, we haveidentified four types of control systems that mediate cardiovascularand motor behavior during exercise. One system increases HRequivalently during both exercise and operantly controlled HR, whereasanother increases HR during both tasks and abolishes operant HRcontrol. In the third system, the effect of brain stimulation on HR is attenuated during exercise and during exercise with operantly controlled HR. The fourth system increases HR in both tasks, but itseffect is significantly attenuated during operant HR control. Webelieve that this last system, which includes the mediodorsal nucleus,nucleus ventralis anterior, and cingulate cortex, plays a significantrole in central command.

     

The role of central command in ventilatory control during static exercise

The role of central command in the respiratory response to 15 min of rhythmic-static (isometric) exercise was studied in humans. Voluntary exercise (VE) was compared with electrically induced exercise (EE) at three different work intensities, i.e. 5%, 15% and 25% of maximal voluntary contraction. A group of 12 volunteers participated in the study and each of them performed six sessions. A session consisted of at least 5 min rest, 15 min rhythmic-static single leg exercise (4 s contraction/12 s relaxation) and at least 5 min recovery. Force, minute ventilation (V _E) and oxygen uptake (VO₂) were measured. In EE, both V _E and VO₂ increased continuously during the entire exercise period after an initial rapid increase at all three work intensities. Correlation between VE and VO₂ was highly significant during EE. During all three work intensities of VE, VE and VO₂ achieved a steady-state after the initial increase. During VE, VE did not correlate as closely with VO₂ as during EE. All these findings indicate that central command was not imperative for an adequate ventilatory response to exercise within all three work intensities investigated. Without the influence of central command, correlation between VE and VO₂ was even better than during VE.     

Kinetics of oxygen uptake and heart rate at onset of exercise in children

Requirements for cellular homeostasis appear to be unchanged between childhood and maturity. We hypothesized, therefore, that the kinetics of O2 uptake (VO2) in the transition from rest to exercise would be the same in young children as in teenagers. To test this, VO2 and heart rate kinetics from rest to constant work rate (75% of the subject's anaerobic threshold) in 10 children (5 boys and 5 girls) aged 7-10 yr were compared with values found in 10 teenagers (5 boys and 5 girls) aged 15-18 yr. Gas exchange was measured breath to breath, and phases I and II of the transition and phase III (steady-state exercise) were evaluated from multiple transitions in each child. Phase I (the VO2 at 20 s of exercise expressed as percent rest-to-steady-state exercise VO2) was not significantly correlated with age or weight [mean value 42.5 +/- 8.9% (SD)] nor was the phase II time constant for VO2 [mean 27.3 +/- 4.7 (SD) s]. The older girls had significantly slower kinetics than the other children but were also found to be less fit. When the teenagers exercised at work rates well below 75% of their anaerobic threshold, phase I VO2 represented a higher proportion of the overall response, but the phase II kinetics were unchanged. The temporal coupling between the cellular production of mechanical work at the onset of exercise and the uptake of environmental O2 appears to be controlled throughout growth in children.     

Control of heart rate variability by cardiac parasympathetic nerve activity during voluntary static exercise in humans with tetraplegia.

Heart rate (HR) is controlled solely by via cardiac parasympathetic outflow in tetraplegic individuals, who lack supraspinal control of sympathetic outflows and circulating catecholamines but have intact vagal pathways. A high-frequency component (HF; at 0.15-0.40 Hz) of the power spectrum of HR variability and its relative value against total power (HF/Total) were assessed using a wavelet transform to identify cardiac parasympathetic outflow. The relative contribution of cardiac parasympathetic and sympathetic outflows to controlling HR was estimated by comparing the HF/Total-HR relationship between age-matched tetraplegic and normal men. Six tetraplegic men with complete cervical spinal cord injury performed static arm exercise at 35% of the maximal voluntary contraction until exhaustion. Although resting cardiac output and arterial blood pressure were lower in tetraplegic than normal subjects, HR, HF, and HF/Total were not statistically different between the two groups. When tetraplegic subjects developed the same force during exercise as normal subjects, HF and HF/Total decreased to 67-90% of the preexercise control and gradually recovered 1.5 min after exercise. The amount and time course of the changes in HF/Total during and after exercise coincided well between both groups. In contrast, the increase in HR at the start of exercise was blunted in tetraplegic compared with normal subjects, and the HR recovery following exercise was also delayed. It is likely that, although the withdrawal response of cardiac parasympathetic outflow is preserved in tetraplegic subjects, sympathetic decentralization impairs the rapid acceleration of HR at the onset of exercise and the rapid deceleration following exercise.     

Central command contributes to increased blood flow in the noncontracting muscle at the start of one-legged dynamic exercise in humans

Whether neurogenic vasodilatation contributes to exercise hyperemia is still controversial. Blood flow to noncontracting muscle, however, is chiefly regulated by a neural mechanism. Although vasodilatation in the nonexercising limb was shown at the onset of exercise, it was unclear whether central command or muscle mechanoreflex is responsible for the vasodilatation. To clarify this, using voluntary one-legged cycling with the right leg in humans, we measured the relative changes in concentrations of oxygenated-hemoglobin (Oxy-Hb) of the noncontracting vastus lateralis (VL) muscle with near-infrared spectroscopy as an index of tissue blood flow and femoral blood flow to the nonexercising leg. Oxy-Hb in the noncontracting VL and femoral blood flow increased (P < 0.05) at the start period of voluntary one-legged cycling without accompanying a rise in arterial blood pressure. In contrast, no increases in Oxy-Hb and femoral blood flow were detected at the start period of passive one-legged cycling, suggesting that muscle mechanoreflex cannot explain the initial vasodilatation of the noncontracting muscle during voluntary one-legged cycling. Motor imagery of the voluntary one-legged cycling increased Oxy-Hb of not only the right but also the left VL. Furthermore, an increase in Oxy-Hb of the contracting VL, which was observed at the start period of voluntary one-legged cycling, had the same time course and magnitude as the increase in Oxy-Hb of the noncontracting muscle. Thus it is concluded that the centrally induced vasodilator signal is equally transmitted to the bilateral VL muscles, not only during imagery of exercise but also at the start period of voluntary exercise in humans.     

Skeletal muscle vasodilation at the onset of exercise

The purpose of this study was to determinewhether -adrenergic or muscarinic receptors are involved in skeletalmuscle vasodilation at the onset of exercise. Mongrel dogs(n = 7) were instrumented with flow probes on both externaliliac arteries and a catheter in one femoral artery. Propranolol (1 mg), atropine (500 µg), both drugs, or saline was infusedintra-arterially immediately before treadmill exercise at 3 miles/h,0% grade. Immediate and rapid increases in iliac blood flow occurredwith initiation of exercise under all conditions. Peak blood flows werenot significantly different among conditions (682 ± 35, 646 ± 49, 637 ± 68, and 705 ± 50 ml/min, respectively). Although thedoses of antagonists employed had no effect on heart rate or systemicblood pressure, they were adequate to abolish agonist-induced increasesin iliac blood flow. Because neither propranolol nor atropine affected iliac blood flow, we conclude that activation of -adrenergic andmuscarinic receptors is not essential for the rapid vasodilation inactive skeletal muscle at the onset of exercise in dogs.

     

Peripheral circulatory factors limit rate of increase in muscle O2 uptake at onset of heavy exercise

We used anexercise paradigm with repeated bouts of heavy forearm exercise to testthe hypothesis that alterations in local acid-base environment thatremain after the first exercise result in greater blood flow andO₂ delivery at the onset of the second bout of exercise.Two bouts of handgrip exercise at 75% peak workload were performed for5 min, separated by 5 min of recovery. We continuously measured bloodflow using Doppler ultrasound and sampled venous blood forO₂ content, PCO₂, pH, and lactateand potassium concentrations, and we calculated muscle O₂uptake (O₂). Forearm blood flow waselevated before the second exercise compared with the first andremained higher during the first 30 s of exercise (234 ± 18 vs. 187 ± 4 ml/min, P < 0.05). Flow was notdifferent at 5 min. Arteriovenous O₂ content difference waslower before the second bout (4.6 ± 0.9 vs. 7.2 ± 0.7 mlO₂/dl) and higher by 30 s of exercise(11.2 ± 0.7 vs. 10.8 ± 0.7 ml O₂/dl,P < 0.05). Muscle O₂was unchanged before the start of exercise but was elevated during thefirst 30 s of the transition to the second exercise bout(26.0 ± 2.1 vs. 20.0 ± 0.9 ml/min, P < 0.05). Changes in venous blood PCO₂, pH, andlactate concentration were consistent with reduced reliance onanaerobic glycolysis at the onset of the second exercise bout. Thesedata show that limitations of muscle blood flow can restrict theadaptation of oxidative metabolism at the onset of heavy muscular exertion.

     

Role of muscular factors in cardiorespiratory responses to static exercise: contribution of reflex mechanisms

We investigated the effects of muscle mass and contractionintensity on the cardiorespiratory responses to static exercise and onthe contribution afforded by muscle metaboreflex and arterial baroreflex mechanisms. Ten subjects performed static handgrip at 30%maximal voluntary contraction (MVC) (SHG-30) and one-leg extension at15% (SLE-15) and 30% (SLE-30) MVC, followed by postexercise circulatory occlusion (PECO). Mean arterial pressure (MAP) and heartrate (HR) responses were greater during SLE-30 than during SHG-30. Thedifference in MAP was maintained by PECO, and the part of the pressorresponse maintained by PECO was greater after SLE-30 than after SHG-30(88.3 ± 10.6 and 67.8 ± 12.7%, respectively, P = 0.02). There were no differences in MAP and HR responses between SHG-30and SLE-15 trials. Baroreflex sensitivity was maintained during SHG-30and SLE-15, whereas it was significantly reduced during SLE-30 andrecovered back to the resting level during PECO. Minute ventilation andoxygen uptake increased more during SLE-30 than during both SHG-30 andSLE-15 trials. Minute ventilation remained significantly elevated aboverest only during PECO following SLE-30. These data suggest that duringstatic exercise the muscle mass and contraction intensity affect1) the magnitude of the cardiorespiratory responses,2) the contribution of muscle metaboreflex to thecardiorespiratory responses, and 3) the arterialbaroreflex contribution to HR control.

     

Physical exercise at night blunts the nocturnal increase of plasma melatonin levels in healthy humans

The effects of physical exercise on nighttime melatonin secretion have never been investigated in humans. For this purpose, plasma melatonin levels were measured at different times during the day and the night in seven healthy men (aged 26-33 yrs), both in resting condition and before and after a physical exercise performed between 10.40 and 11.00 p.m.. The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximal work capacity (MWC) for 10 min, followed by other 10 min of bicycling at 80% of the MWC. The results clearly showed that physical stress at night significantly blunts the nocturnal increase in plasma melatonin levels (group X time interaction: p less than 0.00001; two-way ANOVA with repeated measures). These findings, taken together with the data of the literature, suggest that the response of the pineal gland to provocative stimuli may depend on its level of activity when the stimulus is applied.