INTRODUCTION

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THERE IS CONSIDERABLE EVIDENCE that inputs from the vestibular system have direct effects on the cardiovascular system. Doba and Reis (2) found that the vestibular system is involved in blood pressure regulation during postural changes. They demonstrated that, in paralyzed, anesthetized cats, bilateral transection of the vestibular nerve impairs the reflex changes in blood pressure produced by nose-up tilt. Animal studies have demonstrated increases in sympathetic nerve discharge during stimulation of the vestibular system. Increases in sympathetic outflow have been reported to a number of vascular beds (e.g., renal, splanchnic, and cardiac) (1, 4, 6, 13).

We have demonstrated in humans that head-down neck flexion (HDNF) elicits marked increases in muscle sympathetic nerve activity (MSNA) and calf vascular resistance (8, 10). This increase in MSNA appeared to be related to engagement of the vestibulosympathetic reflex. However, one factor that was not specifically evaluated during these studies was the possible influence of neck muscle afferents. Neck afferents have been reported to play an important role in a number of vestibular reflexes (12).

The purpose of this study was to determine whether neck afferents activated by horizontal neck rotation or flexion alter MSNA in humans. MSNA was measured during head positions that activated neck afferents while not engaging the vestibular system. The results indicate that, during changes in head position which do not generate significant force development of the neck muscles, neck afferents do not regulate MSNA in humans.

	METHODS

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Subjects

Experimental Design

Head yaw rotation (n = 11). With the subject in the prone position, the neck was extended and the chin supported. Thus the face was directed forward and not to the floor. This position places the head in close approximation to its normal orientation when an individual is in the upright posture (10). After a 3-min baseline period with the head in the upright position, subjects rotated their head to the side (~90°) (yaw rotation) and maintained this position for 3 min. Yaw rotation was performed by the subjects while they were in both the prone (n = 5) and sitting (n = 6) positions. During the trials with the subjects in the prone position, the head was rotated and supported by an investigator. The transition time from the baseline position to complete yaw rotation was ~1-2 s. The head returned to the baseline position after the 3-min yaw rotation for a 3-min recovery period. Yaw rotation does not engage the otolith organs because the head is being moved in the horizontal plane with respect to gravity and the static position of the head prevents stimulation of the semicircular canals.

Neck flexion in lateral position (n = 5). Subjects were positioned lying on their right side (i.e., lateral decubitus). The baseline head position was with the dorsal aspect of the head aligned with the back. After 3 min in this position, the head was moved into neck flexion. Neck flexion (chin to chest) was performed for 3 min. These experiments were conducted to mimic the action of neck flexion used in our previous studies (8, 10) while not engaging the vestibular system (i.e., no activation of the otolith organs and semicircular canals).

Head-down neck flexion (n = 9). The same prone posture as previously described for yaw rotation was used. After 3 min of baseline, the chin support was removed and the head was passively lowered to the HDNF position (head lowered over table with the chin held against the chest). The transition time from the chin-supported position to HDNF was between 3 and 5 s. After 3 min, the head was returned to the chin-supported baseline position for a 3-min recovery period.

Measurements

Sympathetic bursts were identified by visual inspection of the mean voltage neurogram. MSNA was expressed as both burst frequency (bursts/min) and the sum of the area of those bursts per minute (total activity; expressed as arbitrary units). The area of the sympathetic bursts was measured by a computer program (Peaks, AD Instruments, Milford, MA).

Continuous measurements of arterial blood pressure and heart rate were made by using a Finapres blood pressure monitoring unit (Ohmeda, Englewood, CO). Calf blood flow was measured by venous occlusion strain-gauge plethysmography (EC 4 plethysmograph, Hokanson, Bellevue, WA) by using a mercury-in-Silastic strain gauge. The strain gauge was placed around the largest area of the calf. Circulation to the foot was arrested by inflating a cuff around the ankle to 200 mmHg during determinations of calf blood flow. The pressure of the venous occlusion cuff around the upper leg was 50 mmHg. Calf blood flow was measured at 15-s intervals. Calf vascular resistance was calculated by dividing mean arterial pressure by calf blood flow. All data were collected online (MacLab 8e, AD Instruments) with a Macintosh computer (Quadra 840AV).

Data Analysis

	RESULTS

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Responses for all variables to yaw rotation are presented in Table 1. MSNA, expressed as burst frequency or total activity, was unchanged by yaw rotation. Calf blood flow and calf vascular resistance were also unchanged by yaw rotation. Heart rate (64 ± 3 to 66 ± 3 beats/min; P = 0.058) and mean arterial pressure (90 ± 3 to 93 ± 3 mmHg; P < 0.01) increased slightly during head rotation.

Neck flexion by the subjects in the lateral position did not elicit any significant changes in MSNA, heart rate, and mean arterial pressure (Table 2). However, HDNF elicited a marked increase in MSNA (Table 3). MSNA, expressed as burst frequency, increased from 13 ± 2 to 19 ± 3 bursts/min (P = 0.0001) and total MSNA increased from 148 ± 29 to 255 ± 50 units/min (P = 0.0002) during HDNF. There were no significant changes in heart rate and mean arterial pressure.

Figure 1 shows a comparison of the change in MSNA from baseline averaged over the 3 min of each head movement. Only HDNF elicited a significant increase in MSNA (79 ± 12%; P = 0.0001). This response was significantly greater than the response elicited by yaw rotation and neck flexion performed by the subjects in the lateral decubitus position. There was no significant difference between MSNA responses to yaw rotation and lateral neck flexion (P = 0.3235). An original recording of MSNA from one subject during the three head positions is presented in Fig. 2.

View larger version (16K): [in this window] [in a new window]   Fig. 1.   Comparison of changes in muscle sympathetic nerve activity (MSNA) due to different head positions. LNF, neck flexion in lateral decubitus position; HDNF, head-down neck flexion. P values represent comparison from baseline. * Significantly different from yaw and LNF trials.

	DISCUSSION

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The purpose of this study was to determine whether neck afferents regulate MSNA in humans. The results indicate that neck afferents do not regulate MSNA in humans during changes in head position that do not generate significant force development of the neck muscles.

Animal studies have shown that stimulation of neck muscles and the labyrinth effectively cancel each other with regard to the vestibulospinal reflexes (12). Similarly, vestibular neuron responses from vestibular and neck afferent stimulations have also been shown to cancel each other (5). Limb muscles are affected by the interaction of the labyrinth and neck afferents. It has been shown, in some conditions, that this interaction cancels each other; whereas in other conditions the reflex response is augmented (9). Because of these interactive effects of neck afferents with other vestibular reflexes, it was possible that neck afferents were playing a role in regulating sympathetic outflow and, therefore, confounded our interpretations from our earlier studies, in which we found increases in MSNA during HDNF (8, 10). The evidence from our previous studies suggested that the increase in MSNA during HDNF was mediated by the vestibular system, in particular the otolith organs. However, the influence of neck afferents was not systematically evaluated during these studies.

In the present study, we conducted experiments that would activate neck afferents while not engaging the vestibular system. This was accomplished by moving the head in the horizontal plane, which prevents activation of the otolith organs, and by holding the head in a static position, which prevents stimulation of the semicircular canals. Both yaw rotation and neck flexion by the subjects in the lateral position did not change MSNA. These findings strongly indicate that neck afferents activated by pitch and yaw head movements do not play an important role in regulating MSNA in humans. Additionally, these findings support the conclusion of Essandoh et al. (3), who argued against neck reflexes playing an important role in eliciting changes in limb vascular resistance during HDNF. They based their argument on the finding that neck flexion by subjects in the supine position did not change limb resistance in three of the subjects. However, it should be noted that neck flexion by subjects in the supine position would be expected to decrease and not increase MSNA during head-up maneuvers. We have demonstrated this decrease in MSNA when the head was returned to the normal erect position after HDNF in our present and previous studies (8, 10).

We demonstrated significant increases in MSNA during HDNF. These results reconfirm our earlier findings (10). A comparison of the MSNA responses during neck flexion by subjects in the lateral and prone position strongly suggests that neck afferents do not mediate increases in MSNA during HDNF. Unlike neck flexion performed in the lateral decubitus position, HDNF stimulates the otolith organs. Our results in humans are in concert with studies conducted in the cat which indicate that the vestibulosympathetic reflex is primarily mediated by the otolith organs (13).

View larger version (21K): [in this window] [in a new window]   Fig. 2.   Original recordings of MSNA from 1 subject during yaw rotation, LNF, and HDNF. It should be noted that recordings of MSNA for yaw rotation and HDNF were taken during the same experimental session.

A small but significant increase in heart rate (2 beats/min) and mean arterial pressure (3 mmHg) was observed during yaw rotation. These findings suggest that neck afferents may have a small effect on other cardiovascular responses besides MSNA. The increase in mean arterial pressure may be mediated by an increase in sympathetic outflow to other vascular beds (i.e., splanchnic and renal). It would not be surprising to find that neck afferents might elicit differential sympathetic outflow to vascular beds on the basis of their differential effects on limb muscles (9) and other reflexes (5, 12). We have shown that stimulation of otolith organs by HDNF produces differential sympathetic outflow with increases in MSNA but not skin sympathetic nerve activity (8, 10).

We do not believe the small increase in mean arterial pressure observed during yaw rotation was the reason why MSNA did not increase. First, in our earlier study (10), MSNA was increased despite a small increase in mean arterial pressure. Second, when examining our data minute by minute, we found no relationship between changes in mean arterial pressure and MSNA. Third, if baroreflex buffering of MSNA was indeed preventing an increase in MSNA when neck afferents were stimulated, MSNA would have been significantly increased during our neck flexion experiments performed by subjects in the lateral position when arterial pressure was not changed; however, this was not the case.

In the present study, neck afferents were activated by either rotating the head to the side or neck flexion; thus our findings are limited to those head positions that do not generate marked tension on the neck. It has been demonstrated that neck muscles can generate substantial cardiovascular responses during high-force development (7).

In summary, we found that neck afferents activated by neck flexion and yaw rotation do not significantly alter MSNA and calf vascular resistance in humans. These findings support the concept that increases in MSNA elicited by HDNF are due to the engagement of the vestibular system. Future studies examining the contribution of vestibulosympathetic reflex to blood pressure regulation in humans warrant investigation.