Effect of thermal stress on the vestibulosympathetic reflexes in humans

Both heat stress and vestibular activation alter autonomic responses; however, the interaction of these two sympathetic activators is unknown. To determine the effect of heat stress on the vestibulosympathetic reflex, eight subjects performed static head-down rotation (HDR) during normothermia and whole body heating. Muscle sympathetic nerve activity (MSNA; peroneal microneurography), mean arterial blood pressure (MAP), heart rate (HR), and internal temperature were measured during the experimental trials. HDR during normothermia caused a significant increase in MSNA (Δ5 ± 1 bursts/min; Δ53 ± 14 arbitrary units/min), whereas no change was observed in MAP, HR, or internal temperature. Whole body heating significantly increased internal temperature (Δ0.9 ± 0.1°C), MSNA (Δ10 ± 3 bursts/min; Δ152 ± 44 arbitrary units/min), and HR (Δ25 ± 6 beats/min), but it did not alter MAP. HDR during whole body heating increased MSNA (Δ16 ± 4 bursts/min; Δ233 ± 90 arbitrary units/min from normothermic baseline), which was not significantly different from the algebraic sum of HDR during normothermia and whole body heating (Δ15 ± 4 bursts/min; Δ205 ± 55 arbitrary units/min). These data suggest that heat stress does not modify the vestibulosympathetic reflex and that both the vestibulosympathetic and thermal reflexes are robust, independent sympathetic nervous system activators.

Anatomic patterning in the expression of vestibulosympathetic reflexes

To investigate the possibility that expression of vestibulosympathetic reflexes (VSR) is related to a nerve's anatomic location rather than its target organ, we compared VSR recorded from the same type of postganglionic fiber [muscle vasoconstrictor (MVC)] located at three different rostrocaudal levels: hindlimb, forelimb, and face. Experiments were performed on chloralose-anesthetized cats, and vestibular afferents were stimulated electrically. Single MVC unit activity was extracted by spike shape analysis of few-fiber recordings, and unit discrimination was confirmed by autocorrelation. Poststimulus time histogram analysis revealed that about half of the neurons were initially inhibited by vestibular stimulation (type 1 response), whereas the other MVC fibers were initially strongly excited (type 2 response). MVC units with types 1 and 2 responses were present in the same nerve fascicle. Barosensitivity was equivalent in the two groups, but fibers showing type 1 responses fired significantly faster than those giving type 2 responses (0.29 ± 0.04 vs. 0.20 ± 0.02 Hz). Nerve fibers with type 1 responses were most common in the hindlimb (21 of 29 units) and least common in the face (2 of 11 units), the difference in relative proportion being significant ( P < 0.05, χ2 test). These results support the hypothesis that VSR are anatomically patterned.

Vestibular stimulation leads to distinct hemodynamic patterning

Previous studies demonstrated that responses of a particular sympathetic nerve to vestibular stimulation depend on the type of tissue the nerve innervates as well as its anatomic location. In the present study, we sought to determine whether such precise patterning of vestibulosympathetic reflexes could lead to specific hemodynamic alterations in response to vestibular afferent activation. We simultaneously measured changes in systemic blood pressure and blood flow (with the use of Doppler flowmetry) to the hindlimb (femoral artery), forelimb (brachial artery), and kidney (renal artery) in chloralose-urethane-anesthetized, baroreceptor-denervated cats. Electrical vestibular stimulation led to depressor responses, 8 ± 2 mmHg (mean ± SE) in magnitude, that were accompanied by decreases in femoral vasoconstriction (23 ± 4% decrease in vascular resistance or 36 ± 7% increase in vascular conductance) and increases in brachial vascular tone (resistance increase of 10 ± 6% and conductance decrease of 11 ± 4%). Relatively small changes (<5%) in renal vascular tone were observed. In contrast, electrical stimulation of muscle and cutaneous afferents produced pressor responses (20 ± 6 mmHg) that were accompanied by vasoconstriction in all three beds. These data suggest that vestibular inputs lead to a complex pattern of cardiovascular changes that is distinct from that which occurs in response to activation of other types of somatic afferents.

Patterning of somatosympathetic reflexes

In a previous study, we reported that vestibular nerve stimulation in the cat elicits a specific pattern of sympathetic nerve activation, such that responses are particularly large in the renal nerve. This patterning of vestibulosympathetic reflexes was the same in anesthetized and decerebrate preparations. In the present study, we report that inputs from skin and muscle also elicit a specific patterning of sympathetic outflow, which is distinct from that produced by vestibular stimulation. Renal, superior mesenteric, and lumbar colonic nerves respond most strongly to forelimb and hindlimb nerve stimulation (∼60% of maximal nerve activation), whereas external carotid and hypogastric nerves were least sensitive to these inputs (∼20% of maximal nerve activation). In contrast to vestibulosympathetic reflexes, the expression of responses to skin and muscle afferent activation differs in decerebrate and anesthetized animals. In baroreceptor-intact animals, somatosympathetic responses were strongly attenuated (to <20% of control in every nerve) by increasing blood pressure levels to >150 mmHg. These findings demonstrate that different types of somatic inputs elicit specific patterns of sympathetic nerve activation, presumably generated through distinct neural circuits.

Regional and functional differences in the distribution of vestibulosympathetic reflexes

Although considerable evidence suggests that the vestibular system regulates sympathetic outflow during movement and changes in posture, little is known about relative vestibular influences on activity of different sympathetic nerves and sympathetic efferents with different functions. In the present study, we demonstrated that electrical stimulation of the vestibular nerve in the cat elicited responses in sympathetic nerves innervating the head and abdominal viscera. This observation suggests that activity of sympathetic efferents innervating multiple body regions is affected by vestibular signals. These responses were attenuated by >80% when blood pressure was increased to >160 mmHg. Because raising blood pressure decreases the responsiveness of vasoconstrictor fibers, the simplest explanation for these data is that the vestibular system provides particularly strong inputs to components of the sympathetic nervous system that regulate peripheral vascular resistance. Furthermore, the relative magnitude of vestibulosympathetic reflexes was over four times larger in one sympathetic nerve composed mainly of vasoconstrictor efferents (renal nerve) than another nerve (external carotid nerve) containing similar types of fibers. Collectively, these data indicate that the vestibular system has selective influences on sympathetic outflow to particular tissues and body regions.

Sympathetic and vascular responses to head-down neck flexion in humans

Animal studies have demonstrated increases in sympathetic nerve outflow with vestibular stimulation. The purpose of the present study was to determine whether vestibulosympathetic reflexes are engaged in humans. Muscle sympathetic nerve activity (MSNA), heart rate, arterial pressure, calf blood flow (CBF), and calculated calf vascular resistance (CVR; mean arterial pressure/CBF) were determined during 10 min of baseline (laying prone with chin supported) and 10 min of head-down neck flexion (HDNF). MSNA responses were measured in nine subjects, and calf vascular responses were determined in seven of these subjects. Heart rate increased during the first minute of HDNF (71 +/- 2 to 76 +/- 3 beats/min; P < 0.05) and remained slightly elevated (71 +/- 2 to 74 +/- 3 beats/min; P < 0.05) for the duration of HDNF. Diastolic and mean arterial pressures also increased slightly with HDNF (80 +/- 3 to 82 +/- 3 and 96 +/- 3 to 98 +/- 3 mmHg, respectively; P < 0.05). Systolic arterial pressure did not change significantly during HDNF. CBF decreased 14% (4.63 +/- 0.78 to 3.97 +/- 0.60 ml x min(-1) x 100 ml(-1); P < 0.05), and CVR increased 12% (24.0 +/- 4.3 to 27.4 +/- 4.7 units; P < 0.05) during HDNF. These changes corresponded with significant increases in MSNA during HDNF. MSNA, expressed as burst frequency, increased from 14 +/- 2 to 20 +/- 2 bursts/min (P < 0.05) and increased 63 +/- 23% (P < 0.05) when expressed as the percent change in total activity. All variables returned to baseline during recovery. Thoracic impedance measured in five subjects did not change during HDNF (19.6 +/- 1.2 to 19.7 +/- 1.5 omega), suggesting no major change in central blood volume. The results indicate that HDNF elicits increases in CVR that are mediated by the augmentation of MSNA. Arterial pressure responses and thoracic impedance data suggest that high and low pressure baroreflexes were not the mechanism for sympathetic activation. The immediate increase in MSNA with HDNF suggests a role for vestibulosympathetic reflexes.

Processing of vestibular and other inputs by the caudal ventrolateral medullary reticular formation

Lesions of the lateral medullary reticular formation caudal to the obex abolish vestibulosympathetic and somatosympathetic responses; this area also contains neurons that mediate baroreceptor reflexes. Recordings were made from neurons in the caudal medullary reticular formation of cats that were decerebrate or anesthetized using alpha-chloralose-urethan to determine whether common neurons responded to electrical stimulation of vestibular and hindlimb afferents and had cardiac-related (i.e., baroreceptor) inputs. Many neurons in the ventrolateral portion of the caudal reticular formation received labyrinthine inputs, and they were interspersed with neurons that received baroreceptor signals. However, virtually none of the units received convergent baroreceptor and vestibular inputs, suggesting that separate pathways from the caudal ventrolateral medulla mediate baroreceptor and vestibulosympathetic reflexes. Furthermore, the neurons that received labyrinthine signals could not be antidromically activated from electrodes inserted into the rostral ventrolateral medulla, which is known to mediate vestibulosympathetic responses; thus an indirect pathway must convey vestibular inputs from the caudal to rostral medullary reticular formation. Over 75% of both neurons with baroreceptor inputs and cells with vestibular signals responded to sciatic nerve stimulation, suggesting that more than one pathway from the caudal medulla may mediate somatosympathetic responses.

Organization of vestibular inputs to nucleus tractus solitarius and adjacent structures in cat brain stem

The vestibular system is involved in maintaining stable blood pressure and respiration during changes in posture and is essential for eliciting motion sickness-related vomiting. Because the nucleus tractus solitarius (NTS) participates in the regulation of sympathetic and inspiratory outflow and the triggering of emesis, we tested the hypothesis that this region receives vestibular inputs in cats. In one set of experiments, microinjections of the tracer Phaseolus vulgaris leucoagglutinin into the medial and inferior vestibular nuclei labeled projections to the middle and lateral regions of the NTS. In electrophysiological experiments, electrical stimulation of the vestibular nerve modified the firing rates of neurons located in the same regions. Some neurons with vestibular inputs received convergent signals from the abdominal vagus nerve and could potentially mediate motion sickness-related vomiting. Others received convergent baroreceptor inputs and could act as a substrate for some components of vestibulosympathetic reflexes. In contrast, inspiratory neurons in the dorsal respiratory group received little vestibular input, suggesting that vestibulorespiratory reflexes are mediated by cells located elsewhere.

Properties of sympathetic reflexes elicited by natural vestibular stimulation: implications for cardiovascular control

1. To study the properties of vestibulosympathetic reflexes we recorded outflow from the splanchnic nerve during natural vestibular stimulation in multiple vertical planes in decerebrate cats. Most of the animals were cerebellectomized, although some responses were recorded in cerebellum-intact preparations. Vestibular stimulation was produced by rotating the head in animals whose upper cervical dorsal roots were transected to remove inputs from neck receptors; a baroreceptor denervation and vagotomy were also performed to remove visceral inputs. 2. The plane of head rotation that produced maximal modulation of splanchnic nerve activity (response vector orientation) was measured at 0.2–0.5 Hz. The dynamics of the response were then studied with sinusoidal (0.05- to 1-Hz) stimuli aligned with this orientation. 3. Typically, maximal modulation of splanchnic nerve outflow was elicited by head rotations in a plane near pitch; nose-up rotations produced increased outflow and nose-down rotations reduced nerve discharges. The gains of the responses remained relatively constant across stimulus frequencies and the phases were consistently near stimulus position, like regularly firing otolith afferents. Similar response dynamics were recorded in cerebellectomized and cerebellum-intact animals. 4. The splanchnic nerve responses to head rotation could be abolished by microinjections of the excitotoxin kainic acid into the medial and inferior vestibular nuclei, which is concordant with the responses resulting from activation of vestibular receptors. 5. The properties fo vestibulosympathetic reflexes recorded from the splanchnic nerve support the hypothesis that the vestibular system participates in compensating for posturally related changes in blood pressure.