Respiratory modulation of human autonomic function on Earth.

KEY POINTS: We studied healthy supine astronauts on Earth with electrocardiogram, non-invasive arterial pressure, respiratory carbon dioxide concentrations, breathing depth and sympathetic nerve recordings. The null hypotheses were that heart beat interval fluctuations at usual breathing frequencies are baroreflex mediated, that they persist during apnoea, and that autonomic responses to apnoea result from changes of chemoreceptor, baroreceptor or lung stretch receptor inputs. R-R interval fluctuations at usual breathing frequencies are unlikely to be baroreflex mediated, and disappear during apnoea. The subjects' responses to apnoea could not be attributed to changes of central chemoreceptor activity (hypocapnia prevailed); altered arterial baroreceptor input (vagal baroreflex gain declined and muscle sympathetic nerve burst areas, frequencies and probabilities increased, even as arterial pressure climbed to new levels); or altered pulmonary stretch receptor activity (major breathing frequency and tidal volume changes did not alter vagal tone or sympathetic activity). Apnoea responses of healthy subjects may result from changes of central respiratory motoneurone activity. ABSTRACT: We studied eight healthy, supine astronauts on Earth, who followed a simple protocol: they breathed at fixed or random frequencies, hyperventilated and then stopped breathing, as a means to modulate and expose to view important, but obscure central neurophysiological mechanisms. Our recordings included the electrocardiogram, finger photoplethysmographic arterial pressure, tidal volume, respiratory carbon dioxide concentrations and peroneal nerve muscle sympathetic activity. Arterial pressure, vagal tone and muscle sympathetic outflow were comparable during spontaneous and controlled-frequency breathing. Compared with spontaneous, 0.1 and 0.05 Hz breathing, however, breathing at usual frequencies (∼0.25 Hz) lowered arterial baroreflex gain, and provoked smaller arterial pressure and R-R interval fluctuations, which were separated by intervals that were likely to be too short and variable to be attributed to baroreflex physiology. R-R interval fluctuations at usual breathing frequencies disappear during apnoea, and thus cannot provide evidence for the existence of a central respiratory oscillation. Apnoea sets in motion a continuous and ever changing reorganization of the relations among stimulatory and inhibitory inputs and autonomic outputs, which, in our study, could not be attributed to altered chemoreceptor, baroreceptor, or pulmonary stretch receptor activity. We suggest that responses of healthy subjects to apnoea are driven importantly, and possibly prepotently, by changes of central respiratory motoneurone activity. The companion article extends these observations and asks the question, Might terrestrial responses to our 20 min breathing protocol find expression as long-term neuroplasticity in serial measurements made over 20 days during and following space travel?

Respiratory modulation of human autonomic function: long-term neuroplasticity in space.

KEY POINTS: We studied healthy astronauts before, during and after the Neurolab Space Shuttle mission with controlled breathing and apnoea, to identify autonomic changes that might contribute to postflight orthostatic intolerance. Measurements included the electrocardiogram, finger photoplethysmographic arterial pressure, respiratory carbon dioxide levels, tidal volume and peroneal nerve muscle sympathetic activity. Arterial pressure fell and then rose in space, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations rose and then fell in space, and descended to preflight levels upon return to Earth. Sympathetic burst frequencies (but not areas) were greater than preflight in space and on landing day, and astronauts' abilities to modulate both burst areas and frequencies during apnoea were sharply diminished. Spaceflight triggers long-term neuroplastic changes reflected by reciptocal sympathetic and vagal motoneurone responsiveness to breathing changes. ABSTRACT: We studied six healthy astronauts five times, on Earth, in space on the first and 12th or 13th day of the 16 day Neurolab Space Shuttle mission, on landing day, and 5-6 days later. Astronauts followed a fixed protocol comprising controlled and random frequency breathing and apnoea, conceived to perturb their autonomic function and identify changes, if any, provoked by microgravity exposure. We recorded the electrocardiogram, finger photoplethysmographic arterial pressure, tidal carbon dioxide concentrations and volumes, and peroneal nerve muscle sympathetic activity on Earth (in the supine position) and in space. (Sympathetic nerve recordings were made during three sessions: preflight, late mission and landing day.) Arterial pressure changed systematically from preflight levels: pressure fell during early microgravity exposure, rose as microgravity exposure continued, and drifted back to preflight levels after return to Earth. Vagal metrics changed in opposite directions: vagal baroreflex gain and two indices of vagal fluctuations (root mean square of successive normal R-R intervals; and proportion of successive normal R-R intervals greater than 50 ms, divided by the total number of normal R-R intervals) rose significantly during early microgravity exposure, fell as microgravity exposure continued, and descended to preflight levels upon return to Earth. Sympathetic mechanisms also changed. Burst frequencies (but not areas) during fixed frequency breathing were greater than preflight in space and on landing day, but their control during apnoea was sharply altered: astronauts increased their burst frequencies from already high levels, but they could not modulate either burst areas or frequencies appropriately. Space travel provokes long-lasting sympathetic and vagal neuroplastic changes in healthy humans.

Human sympathetic outflows to skin and muscle target organs fluctuate concordantly over a wide range of time-varying frequencies.

Frequency-domain analyses of simultaneously recorded skin and muscle sympathetic nerve activities may yield unique information on otherwise obscure central processes governing human neural outflows. We used wavelet transform and wavelet phase coherence methods to analyse integrated skin and muscle sympathetic nerve activities and haemodynamic fluctuations, recorded from nine healthy supine young men. We tested two null hypotheses: (1) that human skin and muscle sympathetic nerve activities oscillate congruently; and (2) that whole-body heating affects these neural outflows and their haemodynamic consequences in similar ways. Measurements included peroneal nerve skin and tibial nerve muscle sympathetic activities; the electrocardiogram; finger photoplethysmographic arterial pressure; respiration (controlled at 0.25 Hz, and registered with a nasal thermistor); and skin temperature, sweating, and laser-Doppler skin blood flow. We made recordings at ∼27°C, for ∼20 min, and then during room temperature increases to ∼38°C, over 35 min. We analysed data with a wavelet transform, using the Morlet mother wavelet and wavelet phase coherence, to determine the frequencies and coherences of oscillations over time. At 27°C, skin and muscle nerve activities oscillated coherently, at ever-changing frequencies between 0.01 and the cardiac frequency (∼1 Hz). Heating significantly augmented oscillations of skin sympathetic nerve activity and skin blood flow, arterial pressure, and R-R intervals, over a wide range of low frequencies, and modestly reduced coordination between skin and muscle sympathetic oscillations. These results suggest that human skin and muscle sympathetic motoneurones are similarly entrained by external influences, including those of arterial baroreceptors, respiration, and other less well-defined brainstem oscillators. Our study provides strong support for the existence of multiple, time-varying central sympathetic neural oscillators in human subjects.

Long-term dry immersion: review and prospects.

Dry immersion, which is a ground-based model of prolonged conditions of microgravity, is widely used in Russia but is less well known elsewhere. Dry immersion involves immersing the subject in thermoneutral water covered with an elastic waterproof fabric. As a result, the immersed subject, who is freely suspended in the water mass, remains dry. For a relatively short duration, the model can faithfully reproduce most physiological effects of actual microgravity, including centralization of body fluids, support unloading, and hypokinesia. Unlike bed rest, dry immersion provides a unique opportunity to study the physiological effects of the lack of a supporting structure for the body (a phenomenon we call 'supportlessness'). In this review, we attempt to provide a detailed description of dry immersion. The main sections of the paper discuss the changes induced by long-term dry immersion in the neuromuscular and sensorimotor systems, fluid-electrolyte regulation, the cardiovascular system, metabolism, blood and immunity, respiration, and thermoregulation. The long-term effects of dry immersion are compared with those of bed rest and actual space flight. The actual and potential uses of dry immersion are discussed in the context of fundamental studies and applications for medical support during space flight and terrestrial health care.

Slow head-up tilt causes lower activation of muscle sympathetic nerve activity: loading speed dependence of orthostatic sympathetic activation in humans.

Many earlier human studies have reported that increasing the tilt angle of head-up tilt (HUT) results in greater muscle sympathetic nerve activity (MSNA) response, indicating the amplitude dependence of sympathetic activation in response to orthostatic stress. However, little is known about whether and how the inclining speed of HUT influences the MSNA response to HUT, independent of the magnitude of HUT. Twelve healthy subjects participated in passive 30 degrees HUT tests at inclining speeds of 1 degrees (control), 0.1 degrees (slow), and 0.0167 degrees (very slow) per second. We recorded MSNA (tibial nerve) by microneurography and assessed nonstationary time-dependent changes of R-R interval variability using a complex demodulation technique. MSNA averaged over every 10 degrees tilt angle increased during inclination from 0 degrees to 30 degrees , with smaller increases in the slow and very slow tests than in the control test. Although a 3-min MSNA overshoot after reaching 30 degrees HUT was observed in the control test, no overshoot was detected in the slow and very slow tests. In contrast with MSNA, increases in heart rate during the inclination and after reaching 30 degrees were similar in these tests, probably because when compared with the control test, greater increases in plasma epinephrine counteracted smaller autonomic responses in the very slow test. These results indicate that slower HUT results in lower activation of MSNA, suggesting that HUT-induced sympathetic activation depends partially on the speed of inclination during HUT in humans.

Decoding rule from vasoconstrictor skin sympathetic nerve activity to nonglabrous skin blood flow in humans at normothermic rest.

Although an importance of vasoconstrictor skin sympathetic nerve activity (SNA) in control of cutaneous circulation is widely recognized, the decoding rule that translate dynamic fluctuations of vasoconstrictor skin SNA into skin blood flow is not fully understood. In 10 male subjects who rested in supine position under normothermic condition, we measured skin blood flow index (by laser-Doppler flowmetry) at the dorsum pedis, and vasoconstrictor skin SNA (by microneurography) that was confirmed to innervate the same region as the flow index. We determined the transfer and coherence functions from the neural activity input to the flow and quantified the contribution and predictability from the input to output by system engineering technique. The results showed that in frequency-domain analysis, the transfer function from vasoconstrictor skin SNA to skin blood flow had low-pass filter characteristics with 3.6+/-0.1s of pure time delay. The coherence function was approximately 0.5 between 0.01 and 0.1Hz and less above 0.1Hz. In time-domain analysis, the predictability from the SNA to the skin blood flow was approximately 50%. These findings indicate that at normothermic rest, the decoding rule from vasoconstrictor skin SNA to skin blood flow of skin is characterized by low-pass filter with 3-4s of pure time delay, and that the vasoconstrictor skin SNA contributes to a half of fluctuation of skin blood flow in the condition. The incomplete dependence of skin blood flow on vasoconstrictor skin SNA may confirm nonneural mechanisms to control cutaneous circulation even at normothermic rest.

Microneurography as a tool in clinical neurophysiology to investigate peripheral neural traffic in humans.

Microneurography is a method using metal microelectrodes to investigate directly identified neural traffic in myelinated as well as unmyelinated efferent and afferent nerves leading to and coming from muscle and skin in human peripheral nerves in situ. The present paper reviews how this technique has been used in clinical neurophysiology to elucidate the neural mechanisms of autonomic regulation, motor control and sensory functions in humans under physiological and pathological conditions. Microneurography is particularly important to investigate efferent and afferent neural traffic in unmyelinated C fibers. The recording of efferent discharges in postganglionic sympathetic C efferent fibers innervating muscle and skin (muscle sympathetic nerve activity; MSNA and skin sympathetic nerve activity; SSNA) provides direct information about neural control of autonomic effector organs including blood vessels and sweat glands. Sympathetic microneurography has become a potent tool to reveal neural functions and dysfunctions concerning blood pressure control and thermoregulation. This recording has been used not only in wake conditions but also in sleep to investigate changes in sympathetic neural traffic during sleep and sleep-related events such as sleep apnea. The same recording was also successfully carried out by astronauts during spaceflight. Recordings of afferent discharges from muscle mechanoreceptors have been used to understand the mechanisms of motor control. Muscle spindle afferent information is particularly important for the control of fine precise movements. It may also play important roles to predict behavior outcomes during learning of a motor task. Recordings of discharges in myelinated afferent fibers from skin mechanoreceptors have provided not only objective information about mechanoreceptive cutaneous sensation but also the roles of these signals in fine motor control. Unmyelinated mechanoreceptive afferent discharges from hairy skin seem to be important to convey cutaneous sensation to the central structures related to emotion. Recordings of afferent discharges in thin myelinated and unmyelinated fibers from nociceptors in muscle and skin have been used to provide information concerning pain. Recordings of afferent discharges of different types of cutaneous C-nociceptors identified by marking method have become an important tool to reveal the neural mechanisms of cutaneous sensations such as an itch. No direct microneurographic evidence has been so far proved regarding the effects of sympathoexcitation on sensitization of muscle and skin sensory receptors at least in healthy humans.

Attenuated thermoregulatory sweating and cutaneous vasodilation after 14-day bed rest in humans.

We investigated the effect of head-down bed rest (HDBR) for 14 days on thermoregulatory sweating and cutaneous vasodilation in humans. Fluid intake was ad libitum during HDBR. We induced whole body heating by increasing skin temperature for 1 h with a water-perfused blanket through which hot water (42 degrees C) was circulated. The experimental room was air-conditioned (27 degrees C, 30-40% relative humidity). We measured skin blood flow (chest and forearm), skin temperatures (chest, upper arm, forearm, thigh, and calf), and tympanic temperature. We also measured sweat rate by the ventilated capsule method in which the skin area for measurement was drained by dry air conditioned at 27 degrees C under similar skin temperatures in both trials. We calculated cutaneous vascular conductance (CVC) from the ratio of skin blood flow to mean blood pressure. From tympanic temperature-sweat rate and -CVC relationships, we assessed the threshold temperature and sensitivity as the slope response of variables to a given change in tympanic temperature. HDBR increased the threshold temperature for sweating by 0.31 degrees C at the chest and 0.32 degrees C at the forearm, whereas it reduced sensitivity by 40% at the chest and 31% at the forearm. HDBR increased the threshold temperature for cutaneous vasodilation, whereas it decreased sensitivity. HDBR reduced plasma volume by 11%, whereas it did not change plasma osmolarity. The increase in the threshold temperature for sweating correlated with that for cutaneous vasodilation. In conclusion, HDBR attenuated thermoregulatory sweating and cutaneous vasodilation by increasing the threshold temperature and decreasing sensitivity. HDBR increased the threshold temperature for sweating and cutaneous vasodilation by similar magnitudes, whereas it decreased their sensitivity by different magnitudes.

Effects of increased ambient temperature on skin sympathetic nerve activity and core temperature in humans.

The strength of sympathetic vasoconstrictor nerve traffic to the skin has an important role in human thermoregulation since it controls heat loss from the skin by constricting or dilating cutaneous blood vessels. This study sought to clarify the time relationship between a reduction of the vasoconstrictor activity induced by elevating the ambient temperature (Ta), and subsequent change of core temperature (Tty). For this purpose, we recorded peroneal skin sympathetic nerve activity (SSNA), laser Doppler skin blood flow, skin and core (tympanic) temperatures in 11 subjects while increasing Ta from 15 to 30 degrees C during approximately 30 min. We observed a significant suppression of SSNA 7.7 min after Ta rise with marked interindividual variations. Tty displayed an increase with a peak after 8.2 min followed by a successive decrease, which became significant 14 min after the Ta rise. The rate of decrease of vasoconstrictor SSNA correlated both with the rate of decrease of Tty (P<0.01) and the magnitude of the Tty decrease (P<0.0005). A cross-correlogram between SSNA and Tty showed a peak at 7 min (r=0.52). We conclude that a Ta rise-induced reduction of skin vasoconstrictor nerve traffic leads to a core temperature decrease after 7-8 min.

Occurrence of the spinal reflex due to skin pressure in sudomotor and cutaneous vasoconstrictor nerve system of humans.

The effects of skin pressure applied to one side of the waist on sudomotor and vasoconstrictor nerve activity were compared with the effects on sweating and cutaneous blood flow in humans. The sweat rate and cutaneous blood flow were measured on left and right dorsal feet. Skin sympathetic nerve activity (SSNA) was recorded by microneurography from a microelectrode inserted in left and right peroneal nerves. Skin pressure was applied in a supine position to the area over the left or right anterior superior iliac spine under warm (T(a): 30-36 degrees C) and cool (T(a): 19-23 degrees C) conditions. Sudomotor and vasoconstrictor bursts were identified for quantitative analysis. The skin pressure increased the contralateral/ipsilateral ratio of the sweat rate. It also increased the contralateral/ipsilateral ratio of the cutaneous blood flow and the contralateral/ipsilateral ratio of the sudomotor burst amplitude. However, skin pressure did not induce any significant changes in the contralateral/ipsilateral ratio of the vasoconstrictor burst amplitude. The results indicate that an asymmetrical reflex effect of skin pressure on vasoconstrictor nerve activity was absent, suggesting that, whereas the ipsilateral suppression of sweating elicited by skin pressure was mediated by the sudomotor nerve system, the ipsilateral suppression of cutaneous blood flow was not mediated by the vasoconstrictor nerve system. Thus, the occurrence of the spinal reflex due to skin pressure is not uniform between the sudomotor and the vasoconstrictor nerve systems, which represent different organizations at the level of spinal cord.

Autonomic cardiovascular changes during and after 14 days of head-down bed rest.

A 14-day, 6 degrees head-down bed rest (HDBR) study was conducted with 12 healthy young men to determine whether there are transient responses of the cardiovascular autonomic regulatory system including cardiovascular, autonomic nervous, and cardiac baroreceptor reflex functions in the acute phases of HDBR and post-HDBR. Compared with the supine position before bed rest, the high-frequency band power (HF(RRI)) of RR intervals (RRIs) decreased significantly at 3, 6, and 24 h of HDBR. This tendency went on until 24 h post-HDBR. Three kinds of cardiac baroreceptor reflex sensitivity (BRS) were estimated from closed-loop approaches to simultaneously recorded spontaneous RRI and systolic arterial pressure (SAP) fluctuations. BRSsequence is based on the simultaneous changes between RRI and SAP. alphaLF and alphaHF are based on a cross-spectrum analysis for low- and high-frequency bands of RRI and SAP. Although BRSsequence decreased significantly at acute phases of both HDBR and post-HDBR, neither alphaLF nor alphaHF decreased significantly at any of the acute phases of HDBR and post-HDBR. Our results suggest that HF(RRI) and BRSsequence can be used effectively to reveal reductions in cardiac vagal nervous modulation on the sinus node and cardiac BRS within 24 h of both HDBR and post-HDBR.

Syncopal attack alters the burst properties of muscle sympathetic nerve activity in humans.

This study aimed at examining whether the properties of microneurographically recorded muscle sympathetic nerve activity (MSNA) were altered during hypotensive attacks. A retrospective study was performed on 74 subjects who participated in tilt studies when vasodepressive syncope was induced incidentally in six subjects. The specific features of MSNA that distinguish this activity from skin sympathetic nerve activity are (1) rhythmic pulse synchronous burst discharge, (2) a duration of approximately 150-300 ms, and (3) no response to arousal stimuli were abolished during the syncopal attack. The altered features observed during the syncopal attack in these six subjects were (1) scattered reflex latencies of MSNA peak from the ECG R-wave, (2) elongated burst duration twice to five times as long as that in conscious state, and (3) response to arousal stimuli. The reduced input from the baroreceptors due to suppression on the central sympathetic volley proximal to the nucleus tractus solitarius might be attributed to the lost features characteristic of MSNA.

Age-related changes in vasomotor reflex control of calf venous capacitance response to lower body negative pressure in humans.

The present study was performed to test the hypothesis that calf venous capacitance would be reduced by mild gravitational stress through a vasomotor reflex in humans, and this response could be diminished with advancing age. Nine young (31 +/- 1 years, mean +/- SE) and 9 elderly (69 +/- 1 years) healthy males were exposed to a lower body negative pressure (LBNP) of 15 mmHg. Venous occlusion plethysmography was used to measure calf venous capacitance and calf blood flow. Muscle sympathetic nerve activity (MSNA) was recorded microneurographically from the tibial nerve along with cardiovascular variables. It was found that baseline MSNA was higher [21 +/- 4 (mean +/- SE) vs. 37 +/- 5 bursts x min(-1), young vs. elderly; p < 0.05] and calf venous capacitance was lower (1.71 +/- 0.12 vs. 1.44 +/- 0.10, ml x 100 ml(-1), young vs. elderly; p < 0.05) in the elderly group. At 15 mmHg-LBNP, heart rate and mean arterial pressure both remained unchanged, MSNA was enhanced, and calf blood flow was reduced in all subjects. Calf venous capacitance during LBNP decreased in the young, but did not change in the elderly. A significant negative correlation between percent changes in MSNA and percent changes in calf venous capacitance existed in the young group (y = 20.171x-11.863, r = 20.682; p = 0.0432), but disappeared in the elderly group. The ratio of percent changes in calf venous capacitance to percent changes in MSNA was markedly lower in the elderly (p < 0.01). In conclusion, these results substantiate our hypothesis that calf venous capacitance is reduced by mild LBNP through the vasomotor reflex, and this response is diminished in the elderly.

Age-related influences of leg vein filling and emptying on blood volume redistribution and sympathetic reflex during lower body negative pressure in humans.

To test the hypothesis that leg vein filling and emptying functions could be impaired with advancing age, which would produce less blood volume redistribution toward the lower body and smaller sympathetic reflex response during mild gravitational stress, 9 young and 10 elderly healthy males were exposed to a lower body negative pressure (LBNP) of 15 mmHg. Venous occlusion plethysmography was used to determine the functions of the leg veins. We found that the baseline venous distensibility index (VDI) was lower (0.057 +/- 0.004 vs. 0.048 +/- 0.003 ml x 100 ml(-1) x mmHg(-1), young vs. elderly; p < 0.05), and half-emptying time (T(1/2)) was shorter (1.6 +/- 0.1 vs. 1.3 +/- 0.1 s, young vs. elderly; p < 0.05) in the elderly. At 15 mmHg-LBNP, VDI was decreased and T(1/2) was shortened significantly in the young group, but only slightly in the elderly group. Neither blood pressure nor heart rate changed significantly in either group. The reduction in peripheral venous pressure, which was recorded from the left antecubital vein at the cubital fossa, was less in the elderly, indicating a smaller decrease in central blood volume during LBNP; however, the enhancement of muscle sympathetic nerve activity was nearly the same as that in the young. We conclude that leg vein filling and emptying functions are impaired in elderly people, producing less blood pooling in the legs and smaller reduction in peripheral venous pressure during LBNP; the maintained sympathetic reflex response might be attributable to the well-preserved baroreflex function control of sympathetic outflow to the muscle in the elderly.

Role of sympathetic nerve activity in the process of fainting.

Syncope is defined as a transient loss of consciousness and postural tone, characterized by rapid onset, short duration, and spontaneous recovery, and the process of syncope progression is here described with two types of sympathetic change. Simultaneous recordings of microneurographically-recorded muscle sympathetic nerve activity (MSNA) and continuous and noninvasive blood pressure measurement has disclosed what is going on during the course of syncope progression. For vasovagal or neurally mediated syncope, three stages are identified in the course of syncope onset, oscillation, imbalance, and catastrophe phases. Vasovagal syncope is characterized by sympathoexcitation, followed by vagal overcoming via the Bezold-Jarisch reflex. Orthostatic syncope is caused by response failure or a lack of sympathetic nerve activity to the orthostatic challenge, followed by fluid shift and subsequent low cerebral perfusion. Four causes are considered for the compensatory failure that triggers orthostatic syncope: hypovolemia, increased pooling in the lower body, failure to activate sympathetic activity, and failure of vasoconstriction against sympathetic vasoconstrictive stimulation. Many pathophysiological conditions have been described from the perspectives of (1) exaggerated sympathoexcitation and (2) failure to activate the sympathetic nerve. We conclude that the sympathetic nervous system can control cardiovascular function, and its failure results in syncope; however, responses of the system obtained by microneurographically-recorded MSNA would determine the pathophysiology of the onset and progression of syncope, explaining the treatment effect that could be achieved by the analysis of this mechanism.

Sympathetic neural influence on bone metabolism in microgravity (Review).

Bone loss is one of the most important complications for astronauts who are exposed to long-term microgravity in space and also for bedridden elderly people. Recent studies have indicated that the sympathetic nervous system plays a role in bone metabolism. This paper reviews findings concerning with sympathetic influences on bone metabolism to hypothesize the mechanism how sympathetic neural functions are related to bone loss in microgravity. Animal studies have suggested that leptin stimulates hypothalamus increasing sympathetic outflow to bone and enhances bone resorption through noradrenaline and ß-adrenoreceptors in bone. In humans, even though there have been some controversial findings, use of ß-adrenoblockers has been reported to be beneficial for prevention of osteoporosis and bone fracture. On the other hand, microneurographically-recorded sympathetic nerve activity was enhanced by exposure to microgravity in space as well as dry immersion or long-term bed rest to simulate microgravity. The same sympathetic activity became higher in elderly people whose bone mass becomes generally reduced. Our recent findings indicated a significant correlation between muscle sympathetic nerve activity and urinary deoxypyridinoline as a specific marker measuring bone resorption. Based on these findings we would like to propose a following hypothesis concerning the sympathetic involvement in the mechanism of bone loss in microgravity: An exposure to prolonged microgravity may enhance sympathetic neural traffic not only to muscle but also to bone. This sympathetic enhancement increases plasma noradrenaline level and inhibits osteogenesis and facilitates bone resorption through ß-adrenoreceptors in bone to facilitate bone resorption to reduce bone mass. The use of ß-adrenoblockers to prevent bone loss in microgravity may be reasonable.