AJP - Heart BIOPAC complete lab solutions
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 280: H237-H245, 2001;
0363-6135/01 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Murata, J.
Right arrow Articles by Matsukawa, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Murata, J.
Right arrow Articles by Matsukawa, K.
Vol. 280, Issue 1, H237-H245, January 2001

Cardiac vagal and sympathetic efferent discharges are differentially modified by stretch of skeletal muscle

Jun Murata and Kanji Matsukawa

Department of Physiology, Institute of Health Sciences, Hiroshima University Faculty of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima City 734-8551, Japan


    ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

We directly measured cardiac vagal efferent nerve activity (CVNA) and cardiac sympathetic efferent nerve activity (CSNA) in cats decerebrated at the level of the precollicular-premammillary body while the hindlimb or the triceps surae muscle was passively stretched. CVNA gradually decreased during passive stretch of the hindlimb, and this decrease was sustained throughout the stretch. CSNA increased at the onset of passive stretch, but this increase was not sustained. CVNA and CSNA responded differentially to graded passive stretches of the triceps surae muscle as well as the hindlimb. The sustained decrease in CVNA but not the initial increase in CSNA became greater depending on muscle length and developed tension. The time course and direction of the cardiac autonomic responses to muscle stretch were not affected by partial sinoaortic denervation, although the magnitude of the CSNA response was augmented. We conclude that the muscle mechanoreflex contributes to differential regulation of cardiac parasympathetic and sympathetic efferent discharges during passive stretch of skeletal muscle irrespective of arterial baroreceptor input.

decerebrate cats; partial sinoaortic denervation; muscle mechanoreflex


    INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

PASSIVE MOVEMENT OF SKELETAL MUSCLE enhances cardiac functions such as heart rate (HR) and cardiac output and increases arterial blood pressure (AP) in conscious humans (1, 24) and anesthetized animals (17, 29). As a mechanism inducing these changes in cardiac function during passive movement, a reflex arising from muscle mechanosensitive afferents activated by the stretch of skeletal muscle is considered. Electrical or chemical stimulation of groups III and IV muscle afferents increases HR, cardiac output, and AP, whereas activation of groups I and II muscle afferents evokes little or insignificant cardiovascular responses (11, 28, 32). In the case of muscle contraction, myelinated group III muscle afferent fibers are more likely to be stimulated by a mechanical event in the contracting skeletal muscle, whereas unmyelinated group IV fibers are more likely to be stimulated by a metabolic product (11, 21). Taken together stimulation of group III mechanosensitive afferents during stretching skeletal muscle may elicit the reflex adjustment of cardiac function via cardiac autonomic nerve activity.

It appears that the cardiac sympathetic nervous system contributes to the reflex control of cardiac function during stretching skeletal muscle, because cardiac sympathetic efferent nerve activity (CSNA) was increased by muscle stretch in anesthetized cats (17). On the other hand, the response of cardiac vagal efferent nerve activity (CVNA) to the stretch of skeletal muscle has not been investigated. HR was increased at the start of muscle contraction evoked by ventral root stimulation in the unanesthetized decerebrate cat, which was blunted after administration of atropine (20). This result suggested that a withdrawal of CVNA is induced by stimulation of muscle mechanosensitive afferents at the start of contraction. It is considered that sympathetic and parasympathetic discharges to the heart show opposite responses during passive stretch. However, to directly identify the reflex cardiac responses, we needed to measure both CVNA and CSNA using unanesthetized animals because general anesthesia influences tonic cardiac autonomic nerve activities and the accompanying baroreflex responses (8, 15). Respiratory sinus arrhythmia, as a noninvasive measure of CVNA, was reduced by thiopental sodium and halothane anesthesia in conscious dogs, although it was preserved during morphine-alpha -chloralose-urethan anesthesia (8). Pentobarbital sodium and alpha -chloralose attenuated tonic and baroreflex cardiac sympathetic outflow in conscious cats (15). These previous results indicate that CVNA and CSNA are strongly affected by any kind of anesthetic agents.

Several research groups have succeeded in recording CVNA in anesthetized dogs and cats either from a cardiac branch of the thoracic vagus (3, 10, 13, 30) or from a filament dissected from the cervical vagus (4, 9, 19, 25). The effect of electrical stimulation of somatic nerves on CVNA has been investigated previously (9, 10, 30). Electrical stimulation of groups II and III cutaneous and muscular afferents induced inhibition of CVNA, which was followed by an increase in CVNA (30). Therefore, it is possible that CVNA is reflexively influenced not only by electrical stimulation of small myelinated muscle afferents but also by mechanical stimulation of skeletal muscle. It is generally thought that the two cardiac sympathetic and vagal neuroregulatory systems have reciprocal functions for the heart. If so, CVNA would decrease and CSNA would increase in response to stretching skeletal muscle. Moreover, the time course of the change in CVNA during the muscle stretch would be expected to have a fixed reciprocal relationship with the time course of the change in CSNA. However, the actual relationship between CVNA and CSNA has been unknown. The purpose of this study was therefore to test, by directly measuring both CVNA and CSNA in unanesthetized decerebrate cats, the hypothesis that cardiac parasympathetic and sympathetic discharges show opposite reflex responses in magnitude and time course when the hindlimb muscles are stretched.


    METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

Preparation

The experiments were performed on 12 cats (2.7 ± 0.1 kg body wt) according to the "Guiding Principles for the Care and Use of Animals in the Fields of Physiological Sciences" approved by the Physiological Society of Japan. Surgery was conducted for implantation of catheters, decerebration, and preparation of the cardiac vagal and sympathetic nerve branches. Anesthesia was introduced by inhalation of a mixture of halothane (4%), N2O, and O2, and then an endotracheal tube was inserted. Subsequently, the cats inhaled the halothane-N2O-O2 mixture through the endotracheal tube during surgery. Electrocardiogram, HR, and respiration were continuously monitored. To maintain the level of surgical anesthesia, the concentration of halothane was increased in a range of 1.0-2.5% if we observed an increase in HR or respiration or withdrawal of the limb in response to a noxious paw pinch or the surgical procedure. Polyvinyl catheters were inserted into the left femoral vein for administering drugs and into the left femoral artery for measuring AP. The left femoral artery catheter was connected to a pressure transducer (DPT III, Baxter). HR was derived from the arterial pressure pulse by a tachometer (model 1321, NEC Sanei). Rectal temperature was maintained at 37-38.5°C with a heating pad and a lamp. The head of the cat was then mounted on a stereotaxic frame. Decerebration was performed by electrocoagulation at the precollicular-premammillary body level as previously described (14, 27). To do this, a stainless steel electrode with insulation removed 5 mm from the tip was inserted into the hypothalamus rostral to the mammillary bodies [from a stereotaxic atlas (2), coordinates from the midpoint of the interaural line were: 13 mm anterior, 6 mm horizontal, and 1-11 mm lateral, with a 14° angle from the perpendicular line]. A negative direct current (1 mA) was passed for 30 s through the electrode. The electrode was withdrawn by 4 mm and the current was passed again. This procedure was repeated for a total of 42 tracks at 0.5-mm intervals. After the decerebration was completed, the cat was removed from the stereotaxic frame. At the end of each experiment the animal was killed by an overdose of pentobarbital sodium and the transected area of the brain was examined histologically. From the histological analysis, the transection that started above the dorsal edge of the diencephalon and extended to the optic chiasma through the thalamus and the hypothalamus was verified. The cerebral cortex, the rostral parts of the thalamus, and the hypothalamus (the anterior hypothalamic area, the supraoptic nucleus, and the rostral part of the lateral hypothalamic area) were disconnected from the brain stem as previously reported (27). Thus the connections between the cerebral cortex and the brain stem were interrupted. The caudal part of the hypothalamus (the posterior hypothalamic area, the caudal part of the lateral hypothalamic area, and the ventromedial nucleus of the hypothalamus) was intact.

Measurement of Cardiac Vagal and Sympathetic Nerve Activities

The cats were placed in the lateral posture. The right thoracotomy was performed. Ribs 1 or 2-5 were removed. The right stellate ganglion was exposed and the nerve bundles of the ventral ansa that extend from the stellate ganglion to the thoracic vagus were identified and cut. For recording cardiac sympathetic discharge (n = 6 cats), a pair of silver wire electrodes were implanted on the central end of the most caudal cut branch of the ventral ansa. Cardiac vagal nerve discharge was measured from a branch of the cardiac vagal nerves that diverge from the right thoracic vagus to the heart; access to the cardiac vagal nerves was reported previously (18). The azygos vein was cut and a cardiac branch of the right vagus nerve was traced to the heart as much as possible. The cardiac vagal branch was cut near the right atrium. To measure cardiac vagal nerve discharge (n = 7 cats), a pair of silver wire electrodes was implanted on the central end of the cut nerve branch; both CVNA and CSNA were measured in one cat. Cardiac vagal discharge was confirmed in two ways, via: 1) augmentation of CVNA when AP was elevated by injection of norepinephrine (3-5 µg/kg iv) or phenylephrine (10-15 µg/kg iv); and 2) abolishment of CVNA after amputation of the right cervical vagus at the end of the experiments.

Original multiunit discharges of CVNA and CSNA were amplified by a differential preamplifier (model S-0476, Nihon Kohden) with a band-pass filter of 50-5,000 Hz. The amplified discharges were converted into standard pulse trains using a digital technique that detects the peaks of the nerve spikes in the original signals (23, 33). The pulse trains were integrated by a resistance-capacitance integrator with a time constant of 20 ms. These integrated signals were used as a monitor of CVNA and CSNA.

After all surgical and preparatory procedures were complete, inhalation anesthesia was stopped. Pancuronium bromide (1-2 mg im) was injected and artificial ventilation was started. After a stabilizing period of a few hours was allowed, the experiment was conducted.

Protocols

Two kinds of muscle stretch were performed to examine the effects on cardiac vagal and sympathetic efferent discharges.

Passive stretch of the hindlimb. The left hindlimb was stretched manually for 180 s in the lateral posture (Fig. 1A). The pelvis was clamped to prevent body-trunk movement during passive stretch of the hindlimb. During the stretch the knee joint was extended from 94 ± 1° to 108 ± 3° and the ankle joint was flexed from 98 ± 3° to 34 ± 2° while the hip-joint angle remained unchanged. From these changes in the joint angles it was estimated that the hamstring muscle was stretched by 9-13 mm and the triceps surae muscle was stretched by 14-17 mm, according to a previous study (5).


View larger version (20K):
[in this window]
[in a new window]
  		Fig. 1.   An experimental setup. A: the cat was placed in the lateral posture and the pelvis was clamped to prevent body movement during passive stretch of the left hindlimb. Hindlimb was stretched manually for 180 s. B: the right triceps surae muscle was isolated and stretched passively (with a manipulator) by 0.5-2 cm for 90 s. Tension during the muscle stretch was measured by connecting the calcaneal tendon to a force transducer. The initial tension loaded to the triceps surae muscle was set at 1 kg.

Passive stretch of the triceps surae muscle. The stretch of the hindlimb might involve stimulation of skin and joint receptors in addition to muscle receptors. To identify the sole effect of stimulation of muscle mechanoreceptors on cardiac vagal and sympathetic efferent discharges, the triceps surae muscle was stretched passively. The pelvis and the knee and toe joints of the right hindlimb were clamped to prevent body-trunk and hindlimb movement during passive muscle stretch, as shown in Fig. 1B. The right triceps surae muscle, calcaneus tendon, and calcaneus bone were exposed. The right triceps surae muscle was isolated from surrounding tissue. The tendon was severed from the calcaneus bone and attached to a force transducer (model LC1205-KC50, A & D). Tension during the stretch of the triceps surae muscle was measured by the force transducer. The initial tension loaded to the triceps surae muscle was set at 1 kg. The triceps surae muscle was stretched for 90 s (with a manipulator) from precisely 0.5-2 cm at 0.5-cm intervals.

Timings at the start and end of stretch for the hindlimb and the triceps surae muscle were manually marked with an electric switch. CVNA or CSNA, AP, HR, muscle tension, and the marking signal for the start and the end of the muscle stretch were continuously recorded on an eight-channel pen-writing recorder (Recti-8K, NEC Sanei) and were also sampled at 400 Hz by a computer. The beat-to-beat calculated parameters of CVNA, CSNA, mean AP (MAP), HR, and muscle tension and the corresponding mean values over 1 s were stored on a hard disk using a customized software program (Cordat II, Data Integrated Scientific Systems, Pinckney, MI) for off-line analysis.

Partial Sinoaortic Denervation and Left Vagotomy

To identify whether the responses of CVNA and CSNA during passive stretch of the hindlimb are influenced by arterial baroreflexes, the responses to the stretch were measured when arterial baroreceptor input was decreased. We performed partial sinoaortic denervation (PSAD) by cutting the bilateral carotid sinus nerves after identifying baroreceptor activity and the left cervical vago-aortic nerve complex in five cats. The right aortic nerve and the cervical vagus were kept intact in these cats. These nerves are fused and become one vagoaortic nerve complex in most cats; therefore the right aortic depressor nerve cannot be distinguished from the cervical vagus. Because of this, we performed PSAD in this study instead of complete SAD. It was reported that the arterial baroreflex inhibition of renal sympathetic nerve activity was significantly impaired by such incomplete amputation of the afferent nerves from arterial baroreceptors, although one of the four baroafferent nerves remained intact (22). The passive stretches of the hindlimb and the triceps surae muscle were repeated according to the same protocols outlined before PSAD and left vagotomy. PSAD was tested by observing the responses of CVNA and CSNA to alterations in MAP induced by bolus injections of norepinephrine (3-5 µg/kg iv) and phenylephrine (10-15 µg/kg iv). Even though the drug-induced changes in MAP became greater with PSAD and left vagotomy, the slope of the MAP-CSNA-relationship curve significantly blunted with PSAD (-0.8 impulse · s-1 · mmHg-1) compared with that without PSAD (-2.5 impulse · s-1 · mmHg-1). The same tendency was also seen in the MAP-CVNA relationship; the slope of the curve with PSAD (0.4 impulse · s-1 · mmHg-1) became smaller (P < 0.05) than that without PSAD (1.8 impulse · s-1 · mmHg-1). These data indicate that the effects of the arterial baroreflexes on cardiac autonomic nerve activity were attenuated by PSAD.

Data Treatment and Statistical Analysis

The data of CVNA, CSNA, MAP, HR, muscle tension, and the marking signal were shown on a computer display, and the beginning and ending of the muscle stretch was visually determined by the marking signal. The average values obtained for 30 s before the onset of muscle stretch were defined as the prestretch baseline levels. Changes in each variable from the prestretch levels were obtained every 1 s for 30 s before, for 180 s during, and for 60 s after the intervention, and the average values over a period of 5 s were sequentially calculated. The data of the changes in CVNA and CSNA were expressed as relative percent changes from the prestretch values, because the absolute values of the baseline CVNA and CSNA varied among animals. The changes in CVNA (percentage), CSNA (percentage), MAP (mmHg), HR (beats/min), and muscle tension (kg) from the baseline levels for an individual animal were aligned at the onset of muscle stretch and were further averaged among animals.

These data of the relative changes were statistically analyzed using one-way ANOVA. When a significant F value in the main effect (time) was present, Dunnett's post hoc test was performed to detect a significant difference between the baseline control level and the value at a given time. Furthermore, in the experimental protocol for passive stretch of the triceps surae muscle, the peak changes in CVNA, CSNA, MAP, and HR detected during muscle stretch were calculated from the original data stored every 1 s for CSNA and from the average data over 5 s for CVNA, MAP, and HR. The peak changes in CVNA, CSNA, MAP, HR, and tension development in response to passive muscle stretch were statistically compared among the four grades of the stretch using one-way ANOVA. If a significant F value in the main effect (extent of muscle stretch) was found, Tukey's post hoc test was performed to detect a significant difference in mean values among the four grades of muscle stretch. The level of statistical significance was defined as P < 0.05. The data are expressed as means ± SE.


    RESULTS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

CVNA and CSNA measurements. The baseline discharges of CVNA and CSNA had bursts synchronized with AP pulse and respiration as shown in Fig. 2. During the cardiac cycle, CVNA appeared near the systolic AP and peaked within 100-150 ms from the systolic AP. CVNA tended to decrease near the peak of respiration-induced fluctuation in AP and tended to increase before or near the bottom of the fluctuation. CSNA mainly appeared in the phase from diastolic AP to systolic AP and was inhibited with a delay of 80-130 ms from systolic AP. CSNA tended to decrease before the bottom of the respiration-induced fluctuation in AP.


View larger version (42K):
[in this window]
[in a new window]
  		Fig. 2.   Example of original multiunit discharges of cardiac vagal efferent nerve activity (CVNA) and cardiac sympathetic efferent nerve activity (CSNA), which were recorded in different cats. Baseline discharges of CVNA and CSNA had bursts synchronized with arterial blood pressure (AP) pulse and respiration. During a cardiac cycle, CVNA appeared around systolic AP and peaked within 100-150 ms from systolic AP. CVNA also tended to decrease near the peak of respiration-induced fluctuation in AP () and increase before or near the bottom of the fluctuation. CSNA mainly appeared in the phase from diastolic AP to systolic AP and was inhibited with a delay of 80-130 ms from systolic AP. CSNA tended to decrease before the bottom of the respiration-induced fluctuation in AP.

CVNA was augmented by intravenous injection of norepinephrine (Fig. 3). The increase in CVNA was caused by profound increases in the occurring frequency and magnitude of bursts synchronized with the AP pulse. The CVNA discharge was eliminated by amputation of the cervical vagus. Using these criteria, cardiac vagal efferent nerve discharge was confirmed.


View larger version (31K):
[in this window]
[in a new window]
  		Fig. 3.   Identification of CVNA. Norepinephrine (2 µg/kg iv) was injected as indicated by arrow (A). CVNA was enhanced by this injection. The same data (A) are reproduced with a faster sweep speed (B, C). Baseline discharge of CVNA had bursts synchronized with respiration and AP pulse (B). After injection of norepinephrine, profound increases in the occurring frequency and magnitude of bursts synchronized with AP pulse were observed in the discharge of CVNA (C). CVNA discharge was eliminated by amputation of the cervical vagus as indicated by the horizontal bar (D).

An example of the responses of CVNA and AP during passive stretch of the hindlimb is shown in Fig. 4. CVNA decreased during stretching of the hindlimb muscles, whereas AP was increased by the stretch. This decrease in CVNA was developed progressively until 30 s from the onset of the stretch and was sustained throughout the stretch of the hindlimb muscles. After the cessation of stretch, CVNA slowly recovered to the baseline level.


View larger version (20K):
[in this window]
[in a new window]
  		Fig. 4.   Example of changes in CVNA and AP during stretching of the left hindlimb in a decerebrate cat. Stretch of hindlimb shows duration of the passive stretch. CVNA decreased and AP increased during the stretch.

Time course of CVNA and CSNA responses during passive stretch of the hindlimb. The baseline values of CVNA and CSNA were 131 ± 1.1 and 87 ± 0.9 impulse/s, respectively; HR and MAP were 158 ± 1.1 beats/min and 112 ± 1.0 mmHg, respectively. Time courses of the responses before, during, and after passive stretch of the hindlimb are shown in Fig. 5. CVNA significantly decreased during the stretch. The decrease in CVNA reached a maximum value of 33 ± 7.7% at 30 s from the onset of the stretch, which was maintained during the later period of the stretch. CVNA returned slowly to the control level after the cessation of the stretch. The decrease in CVNA became insignificant after the end of the stretch and CVNA returned to the control level within 3 min. MAP was significantly increased by 14 ± 3.9 mmHg during the stretch. There was no statistically significant increase in HR.


View larger version (27K):
[in this window]
[in a new window]
  		Fig. 5.   Time course of average changes (Delta ) in CVNA, CSNA, mean AP (MAP), and heart rate (HR) (n = 6-7 cats) before, during, and after passive stretch of the hindlimb. CVNA decreased during the stretch and this decrease reached a maximum value at 30 s from the onset of the stretch. In contrast, CSNA increased only at the onset of the stretch. Values are means ± SE. The horizontal dotted lines show the control levels of individual variables before the hindlimb stretch.

In contrast to the sustained response of CVNA, CSNA was transiently increased by the hindlimb stretch. A significant increase of 47 ± 19.7% in CSNA was obtained only for a brief period immediately after the start of the stretch and was not sustained during the later period of the stretch.

CVNA and CSNA responses during passive stretch of the triceps surae muscle. Figure 6 shows an example of the responses of CVNA, CSNA, AP, and muscle tension to graded passive stretches when the right triceps surae muscle was stretched passively by 1.0-2.0 cm at 0.5-cm intervals. The developed tensions were 4.8-10.4 kg. The decrease in CVNA progressively became greater depending on the extent of the stretch and was maintained during the stretch. On the other hand, the increase in CSNA was observed just after the onset of the stretch, which was unchanged among the three grades of the stretch.


View larger version (24K):
[in this window]
[in a new window]
  		Fig. 6.   Example of the responses of CVNA, CSNA, AP, and muscle tension to graded passive stretches of the right triceps surae muscle. CVNA and CSNA were measured from the same decerebrate cat. The muscle was stretched passively by 1.0-2.0 cm at 0.5-cm intervals. Decrease in CVNA became greater depending on the extent of the stretch (A). However, the initial increase (*) in CSNA was unchanged among the three grades of the stretch (B).

When the right triceps surae muscle was stretched passively by 0.5-2.0 cm at 0.5-cm intervals, the peak responses of CVNA, CSNA, MAP, HR, and muscle tension were measured (Fig. 7). The developed tension of the triceps surae muscle increased progressively from the initial tension of 1.0 kg by 2.9 ± 0.2, 5.1 ± 0.2, 8.2 ± 0.6, and 9.7 ± 0.5 kg, respectively, according to the grade of muscle stretch. The decrease in CVNA became greater from 9 ± 2.5 to 17 ± 4.3% depending on the muscle length and the tension development. However, there was no significant difference in the initial increase in CSNA among the four grades of the stretch (Fig. 7). The increases in MAP and HR were augmented depending on the muscle length and tension development.


View larger version (15K):
[in this window]
[in a new window]
  		Fig. 7.   Peak changes (Delta ) in CVNA, CSNA, MAP, and HR (n = 5 cats) detected during passive stretch of the right triceps surae muscle. When the muscle was passively stretched by 0.5-2.0 cm at 0.5-cm intervals, the decrease in CVNA became greater depending on the muscle length and the tension development but not the CSNA response. Increases in MAP and HR were also augmented depending on the extent of the stretch. Significant differences in peak changes are indicated (*P < 0.05) compared with peak values during 2.0-cm stretch.

Influence of PSAD and left vagotomy. The baseline values of CVNA and CSNA observed after PSAD and left vagotomy were 45 ± 0.5 and 110 ± 0.8 impulse/s, respectively; HR and MAP were 144 ± 0.1 beats/min and 108 ± 0.4 mmHg, respectively. The time courses of their responses during passive stretch of the hindlimb after PSAD and left vagotomy are shown in Fig. 8. CVNA decreased by 35 ± 16.5% during the stretch, and CSNA increased by 86 ± 19.7% at the onset of the stretch. The magnitude of the relative response of CVNA was the same as that of the CVNA response in the intact condition before PSAD and left vagotomy. In contrast, the increase in CSNA during the stretch after PSAD and left vagotomy was greater than before PSAD and left vagotomy (Fig. 8). MAP with PSAD showed a greater increase in response to the stretch (by 47 ± 7.6 mmHg) than MAP without PSAD.


View larger version (28K):
[in this window]
[in a new window]
  		Fig. 8.   Effect of partial sinoaortic denervation and left vagotomy on the responses of CVNA, CSNA, MAP, and HR during passive stretch of the hindlimb (n = 4-5 cats). Relative response of CVNA was similar to that without partial sinoaortic denervation and left vagotomy. On the other hand, the response of CSNA observed at the onset of the stretch was enhanced by partial sinoaortic denervation and left vagotomy. Response of MAP was also augmented. The horizontal dotted lines show the control levels of individual variables before the hindlimb stretch.

The effects of PSAD and left vagotomy on the responses of CVNA, CSNA, and MAP during passive stretch of the triceps surae muscle were similar to the responses shown during stretch of the hindlimb.


    DISCUSSION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

The reflex effects of the stimulation of muscle mechanoreceptors on vagal and sympathetic outflows to the heart have been studied for the first time using unanesthetized, decerebrate cats. Our major new finding is that cardiac vagal outflow is decreased throughout passive stretch of the hindlimb or the triceps surae muscle, whereas cardiac sympathetic outflow is increased only at the start of the passive stretch. The decrease in CVNA and the increase in CSNA were also observed after partial sinoaortic denervation, indicating that the muscle mechanoreflex contributes to the regulation of cardiac parasympathetic and sympathetic nerve discharges during passive stretch, irrespective of arterial baroreceptor input. Furthermore, the finding that the time courses of the responses of cardiac vagal and sympathetic outflows to the stretch were quite different suggests that the two neuroregulatory systems of the heart are differentially modified by skeletal muscle mechanoreceptors.

A technical limitation of the present study is that the right cardiac vagal branch was amputated to eliminate contamination of afferent signals from the heart during the measurement of cardiac vagal efferent discharge. Moreover, cardiac sympathetic nerves that diverged from the right stellate ganglion were also cut to avoid contamination of cardiac sympathetic discharge. Therefore, one of the potential problems in this study is that afferent signals, which should be conveyed from the heart to the central nervous system via the cardiac vagal branch and the cardiac sympathetic nerves, were partly interrupted. A second problem is that the increase in HR in response to passive stretch of the hindlimb or the triceps surae muscle may be underestimated. A third problem is that the triceps surae muscle might be stretched beyond the physiological range when passive tension is greatly developed. Stebbins and colleagues (29) reported that the peak change in passive tension of the triceps surae due to the maximal flexion of the ankle joint was 2.0 kg from the initial resting value, although the knee-joint angle was not recorded. When passive tension of the muscle was measured at various joint angles of the knee and ankle, the maximal absolute tension within the physiological working range was ~3.0-7.0 kg, depending on a set of the knee and ankle joint angles (6, 7). From the comparison between these previous data and the tension responses produced by passive stretch of the triceps surae muscle obtained in this study, it cannot be excluded that passive stretch of the triceps surae muscle with a greater tension development such as a 1.5- to 2.0-cm stretch may be beyond the physiological range of the muscle length and may activate not only mechanoreceptors but also nociceptors. However, it is likely that passive stretch of the muscle with a smaller tension development, such as a 0.5-cm stretch, does not exceed the limit of the physiological range and is able to elicit the reflex responses of CVNA and CSNA. Thus we feel that passive stretch of the muscle within the physiological range is capable of stimulating muscle mechanosensitive afferents, which in turn elicit the reflex effects on cardiac autonomic nerve activity. This is also supported by our data that mechanical stretch (by hand) of the hindlimb produced the same reflex responses of CSNA and CVNA as were obtained during the passive stretch of the triceps surae muscle alone.

Because the decrease in CVNA and the increase in CSNA were produced by passive stretch of the hindlimb within a range of physiological motion, it is likely that CVNA and CSNA are influenced by passive movement that can happen in a natural situation. However, passive stretch of the hindlimb might involve stimulation of cutaneous and joint receptors as well as muscle mechanoreceptors. Accordingly, the triceps surae muscle alone was stretched to identify the sole effect of stimulation of muscle mechanoreceptors on cardiac vagal and sympathetic efferent discharges. The sustained inhibition of CVNA and the brief augmentation of CSNA were also seen during passive stretch of the triceps surae muscle as well as passive stretch of the hindlimb, although the responses of CVNA and CSNA to the stretch of the triceps surae muscle became slightly smaller than during the stretch of the hindlimb. This difference in the responses of CVNA and CSNA is probably caused by a difference in stretched muscle mass. This result indicates that stimulation of skeletal muscle afferents plays an important role in the regulation of cardiac function via the autonomic nervous system during passive body movement. The muscle mechanosensitive reflex may augment the sympathetic outflow controlling other organs, because it has been reported that renal sympathetic outflow is increased by stimulating muscle mechanoreceptors during static contraction (31) and passive stretch (16) in anesthetized cats. Passive stretch of muscle predominantly stimulates mechanoreceptors but not metaboreceptors, because there are no changes in the blood gases, K+, pH, and lactate of muscle venous blood during passive stretch (29). Moreover, passive stretch of muscle excites most group III muscle afferents but fails to activate the majority of group IV muscle afferents (11). The reflex modification of the autonomic nerve activities to the heart, which causes the augmentation in cardiac function, seems to be mediated by activation of group III muscle afferents recruited during passive stretch.

As an autonomic mechanism that is responsible for tachycardia during exercise, it has been postulated that withdrawal of CVNA would be primary and augmentation of CSNA would be secondary contributions to raising HR during exercise (26). If so, the rapid cardiac vagal withdrawal at the start of exercise would be induced by central command or by the muscle mechanoreflex from the contracting muscle. However, in this study, when cardiac parasympathetic and sympathetic outflows were directly measured while skeletal muscles were stretched, the reflex decrease in CVNA was slowly developed and sustained during the muscle stretch. In contrast, the reflex increase in CSNA was observed immediately after the onset of the muscle stretch but was not sustained. Based on the present data, an opposite rationale for the physiological role of the muscle mechanoreflex is considered. The augmentation of CSNA is promptly induced by the muscle mechanoreflex, which in turn produces an initial response of HR at the start of the muscle stretch. On the other hand, the withdrawal of CVNA, which is gradually evoked by the muscle mechanoreflex, contributes to a sustained response in tachycardia during the later period of the muscle stretch.

In general it has been speculated that the responses in the two neuroregulatory (vagal and sympathetic) systems of the heart usually have a fixed reciprocal relationship in magnitude and time course such as the baroreflex responses to stimulation of arterial baroreceptor afferents (12). However, we revealed that the CVNA response during mechanical stretch of skeletal muscle is quite different in the characteristics of magnitude and time course compared with the CSNA response. CVNA was inhibited throughout the passive stretch of the hindlimb or the triceps surae muscle, whereas CSNA was enhanced only at the start of the stretch. Furthermore, the sustained decrease in CVNA but not the initial increase in CSNA was dependent on the muscle length and tension development. These results indicate that cardiac parasympathetic and sympathetic outflows are controlled separately and differentially by the muscle mechanoreflex when stretching skeletal muscle.

Because of a rise in AP by injection of norepinephrine during resting, the arterial baroreflexes cause augmentation of CVNA and inhibition of CSNA, as shown in Fig. 3. We examined whether the responses in CVNA and CSNA during the stretch were affected by the arterial baroreflexes. CVNA was decreased during stretch of the hindlimb or the triceps surae muscle despite an increase in AP. The response of CVNA to the muscle stretch did not change before and after partial sinoaortic denervation. These results demonstrate that the CVNA response is predominantly evoked by stimulation of muscle mechanosensitive afferents but not by arterial baroreceptors. In other words, the arterial baroreflexes seem to have little influence on CVNA in the MAP range of ~110-130 mmHg before and during the passive stretch. Moreover, the increase in CSNA seen at the onset of the muscle stretch preceded the rise in AP, suggesting that this increase in CSNA is induced by the muscle mechanoreflex. However, the response of CSNA was augmented by partial sinoaortic denervation, which indicates that the activation of CSNA during the muscle stretch is restrained by input of arterial baroreceptors due to the elevation of AP. Taken together, the reflexes from arterial baroreceptors mainly influence CSNA rather than CVNA during passive stretch.

Finally, regarding reflex mechanisms of skeletal muscle mechanoreceptors to the cardiac autonomic nerve activities, we conclude that stimulation of mechanosensitive afferents causes a gradual and sustained withdrawal of cardiac vagal outflow, which is quite different from the augmented response of cardiac sympathetic outflow.


    ACKNOWLEDGEMENTS

This study was supported by a grant-in-aid for Scientific Research in the Ministry of Education, Science, and Culture of Japan, a Research Grant for cardiovascular diseases from the Ministry of Health and Welfare of Japan, and a Satake Research Grant from the Hiroshima University Foundation.


    FOOTNOTES

Address for reprint requests and other correspondence: K. Matsukawa, Dept. of Physiology, Institute of Health Sciences, Hiroshima Univ. Faculty of Medicine, Kasumi-cho 1-2-3, Minami-ku, Hiroshima 734-8551, Japan (E-mail: matsu-k{at}mcai.med.hiroshima-u.ac.jp).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 11 April 2000; accepted in final form 10 August 2000.


    REFERENCES
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

1.   Baum, K, Selle K, Leyk D, and Essfeld D. Comparison of blood pressure and heart rate responses to isometric exercise and passive muscle stretch in humans. Eur J Appl Physiol 70: 240-245, 1995.

2.   Berman, AL. The Brain Stem of the Cat: A Cytoarchitectonic Atlas with Stereotaxic Coordinates. Madison, WI: University of Wisconsin Press, 1968.

3.   Cerati, D, and Schwartz PJ. Single cardiac vagal fiber activity, acute myocardial ischemia, and risk for sudden death. Circ Res 69: 1389-1401, 1991[Abstract/Free Full Text].

4.   Davidson, NS, Goldner S, and McCloskey DI. Respiratory modulation of baroreceptor and chemoreceptor reflexes affecting heart rate and cardiac vagal efferent nerve activity. J Physiol (Lond) 259: 523-530, 1976[Abstract/Free Full Text].

5.   Goslow, GE, Jr, Reinking RM, and Stuart DG. The cat step cycle: hindlimb joint angles and muscle lengths during unrestrained locomotion. J Morphol 141: 1-41, 1973[Web of Science][Medline].

6.   Grillner, S. Muscle stiffness and motor control: forces in the ankle during locomotion and standing. In: Motor Control, , edited by Gydikov AA, Tankov NT, and Kosarov DS.. New York: Plenum, 1973, p. 195-215.

7.   Grillner, S. The role of muscle stiffness in meeting the changing postural and locomotor requirements for force development by the ankle extensors. Acta Physiol Scand 86: 92-108, 1972[Web of Science][Medline].

8.   Halliwill, JR, and Billman GE. Effect of general anesthesia on cardiac vagal tone. Am J Physiol Heart Circ Physiol 262: H1719-H1724, 1992[Abstract/Free Full Text].

9.   Iriuchijima, J, and Kumada M. Activity of single vagal fibers efferent to the heart. Jpn J Physiol 14: 479-487, 1964.

10.   Iriuchijima, J, and Kumada M. Efferent cardiac vagal discharge of the dog in response to electrical stimulation of sensory nerves. Jpn J Physiol 13: 599-605, 1963[Web of Science][Medline].

11.   Kaufman, MP, Longhurst JC, Rybicki KJ, Wallach JH, and Mitchell JH. Effects of static muscular contraction on impulse activity of groups III and IV afferents in cats. J Appl Physiol 55: 105-112, 1983[Abstract/Free Full Text].

12.   Kollai, M, and Koizumi K. Cardiac vagal and sympathetic nerve responses to baroreceptor stimulation in the dog. Pflügers Arch 413: 365-371, 1989[Web of Science][Medline].

13.   Kunze, DL. Reflex discharge patterns of cardiac vagal efferent fibres. J Physiol (Lond) 222: 1-15, 1972.

14.   Matsukawa, K, Murata J, and Wada T. Augmented renal sympathetic nerve activity by central command during overground locomotion in decerebrate cats. Am J Physiol Heart Circ Physiol 275: H1115-H1121, 1998[Abstract/Free Full Text].

15.   Matsukawa, K, Ninomiya I, and Nishiura N. Effects of anesthesia on cardiac and renal sympathetic nerve activities and plasma catecholamines. Am J Physiol Regulatory Integrative Comp Physiol 265: R792-R797, 1993[Abstract/Free Full Text].

16.   Matsukawa, K, Wall PT, Wilson LB, and Mitchell JH. Reflex responses of renal nerve activity during isometric muscle contraction in cats. Am J Physiol Heart Circ Physiol 259: H1380-H1388, 1990[Abstract/Free Full Text].

17.   Matsukawa, K, Wall PT, Wilson LB, and Mitchell JH. Reflex stimulation of cardiac sympathetic nerve activity during static muscle contraction in cats. Am J Physiol Heart Circ Physiol 267: H821-H827, 1994[Abstract/Free Full Text].

18.   McAllen, RM, and Spyer KM. The location of cardiac vagal preganglionic motoneurones in the medulla of the cat. J Physiol (Lond) 258: 187-204, 1976[Abstract/Free Full Text].

19.   McCloskey, DI, and Potter EK. Excitation and inhibition of cardiac vagal motoneurones by electrical stimulation of the carotid sinus nerve. J Physiol (Lond) 316: 163-175, 1981[Abstract/Free Full Text].

20.   McMahon, SE, and McWilliam PN. Changes in R-R interval at the start of muscle contraction in the decerebrate cat. J Physiol (Lond) 447: 549-562, 1992[Abstract/Free Full Text].

21.   Mense, S, and Stahnke M. Responses in muscle afferent fibres of slow conduction velocity to contractions and ischaemia in the cat. J Physiol (Lond) 342: 383-397, 1983[Abstract/Free Full Text].

22.   Ninomiya, I, and Irisawa H. Summation of baroceptor reflex effects on sympathetic nerve activities. Am J Physiol 216: 1330-1336, 1969.

23.   Ninomiya, I, Matsukawa K, Honda T, Nishiura N, and Shirai M. Cardiac sympathetic nerve activity and heart rate during coronary occlusion in awake cats. Am J Physiol Heart Circ Physiol 251: H528-H537, 1986[Abstract/Free Full Text].

24.   Nobrega, AC, Williamson JW, Friedman DB, Araujo CG, and Mitchell JH. Cardiovascular responses to active and passive cycling movements. Med Sci Sports Exerc 26: 709-714, 1994[Web of Science][Medline].

25.   Potter, EK. Inspiratory inhibition of vagal responses to baroreceptor and chemoreceptor stimuli in the dog. J Physiol (Lond) 316: 177-190, 1981[Abstract/Free Full Text].

26.   Rowell, LB. Human Cardiovascular Control. New York: Oxford University Press, 1993.

27.   Sadamoto, T, and Matsukawa K. Cardiovascular responses during spontaneous overground locomotion in freely moving decerebrate cats. J Appl Physiol 83: 1454-1460, 1997[Abstract/Free Full Text].

28.   Sato, A, Sato Y, and Schmidt RF. Heart rate changes reflecting modifications of efferent cardiac sympathetic outflow by cutaneous and muscle afferent volleys. J Auton Nerv Syst 4: 231-247, 1981[Web of Science][Medline].

29.   Stebbins, CL, Brown B, Levin D, and Longhurst JC. Reflex effect of skeletal muscle mechanoreceptor stimulation on the cardiovascular system. J Appl Physiol 65: 1539-1547, 1988[Abstract/Free Full Text].

30.   Terui, N, and Koizumi K. Responses of cardiac vagus and sympathetic nerves to excitation of somatic and visceral nerves. J Auton Nerv Syst 10: 73-91, 1984[Web of Science][Medline].

31.   Victor, RG, Rotto DM, Pryor SL, and Kaufman MP. Stimulation of renal sympathetic activity by static contraction: evidence for mechanoreceptor-induced reflexes from skeletal muscle. Circ Res 64: 592-599, 1989[Abstract/Free Full Text].

32.   Waldrop, TG, Rybicki KJ, and Kaufman MP. Chemical activation of group I and II muscle afferents has no cardiorespiratory effects. J Appl Physiol 56: 1223-1228, 1984[Abstract/Free Full Text].

33.   Wiemer, W, Kacck D, Kezdi P, and Klatt H. Peak discrimination as a method for quantitative evaluation of neural activity by computor. Med Biol Eng 13: 337-357, 1975[Web of Science][Medline].

Am J Physiol Heart Circ Physiol 280(1):H237-H245
0363-6135/01 $5.00 Copyright © 2001 the American Physiological Society


This article has been cited by other articles:


Home page
 J. Appl. Physiol.Home page
R. C. Drew, M. P. D. Bell, and M. J. White
Modulation of spontaneous baroreflex control of heart rate and indexes of vagal tone by passive calf muscle stretch during graded metaboreflex activation in humans
J Appl Physiol, March 1, 2008; 104(3): 716 - 723.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
K. Matsukawa and T. Nakamoto
Muscle mechanosensitive reflex is suppressed in the conscious condition: effect of anesthesia
J Appl Physiol, January 1, 2008; 104(1): 82 - 87.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
S. Koba, J. Xing, L. I. Sinoway, and J. Li
Sympathetic nerve responses to muscle contraction and stretch in ischemic heart failure
Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H311 - H321.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. Matsukawa, T. Nakamoto, and A. Inomoto
Gadolinium does not blunt the cardiovascular responses at the onset of voluntary static exercise in cats: a predominant role of central command
Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H121 - H129.
[Abstract] [Full Text] [PDF]

Home page
 Exp PhysiolHome page
K. Tokizawa, M. Mizuno, and I. Muraoka
Forearm vascular responses to combined muscle metaboreceptor activation in the upper and lower limbs in humans
Exp Physiol, July 1, 2006; 91(4): 723 - 729.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
M. Takahashi, A. Sakaguchi, K. Matsukawa, H. Komine, K. Kawaguchi, and K. Onari
Cardiovascular control during voluntary static exercise in humans with tetraplegia
J Appl Physiol, December 1, 2004; 97(6): 2077 - 2082.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
K. Tokizawa, M. Mizuno, Y. Nakamura, and I. Muraoka
Passive triceps surae stretch inhibits vasoconstriction in the nonexercised limb during posthandgrip muscle ischemia
J Appl Physiol, November 1, 2004; 97(5): 1681 - 1685.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
J. Murata, K. Matsukawa, H. Komine, H. Tsuchimochi, and T. Nakamoto
Central inhibition of the aortic baroreceptors-heart rate reflex at the onset of spontaneous muscle contraction
J Appl Physiol, October 1, 2004; 97(4): 1371 - 1378.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
H. Tsuchimochi, K. Matsukawa, H. Komine, and J. Murata
Direct measurement of cardiac sympathetic efferent nerve activity during dynamic exercise
Am J Physiol Heart Circ Physiol, November 1, 2002; 283(5): H1896 - H1906.
[Abstract] [Full Text] [PDF]

Home page
 J. Physiol.Home page
V F Gladwell and J H Coote
Heart rate at the onset of muscle contraction and during passive muscle stretch in humans: a role for mechanoreceptors
J. Physiol., May 1, 2002; 540(3): 1095 - 1102.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (18)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Murata, J.
Right arrow Articles by Matsukawa, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Murata, J.
Right arrow Articles by Matsukawa, K.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online