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To examine the effect of 6 degrees head-down bed rest (HDBR) on vasomotor sympathetic responses to isometric forearm exercise, 16 healthy male subjects aged 20-36 years performed voluntary isometric handgrip (HG) at 30% of maximal voluntary contraction until fatigue, followed by 2 min of post-handgrip muscle ischemia (PHGMI) with 250 mmHg of cuff inflation, before and after 14 days of HDBR. Time to fatigue and maximal voluntary HG force were not affected by HDBR. Pre-exercise baseline muscle sympathetic nerve activity (MSNA, measured by microneurography), heart rate (measured by electrocardiogram) and mean blood pressure (measured by Portapres) increased after HDBR. Increases in MSNA were similar during HG but significantly lower during PHGMI (P0.01) after HDBR. Responses of heart rate and mean blood pressure during HG and PHGMI were not affected by HDBR. These results suggest that the magnitude of muscle metaboreflex during isometric forearm exercise might be attenuated after 14 days of simulated microgravity.

We hypothesized that the relationship between resting levels of sympathetic vasoconstrictor nerve traffic and dilator substance nitric oxide (NO) release is altered after exposure to microgravity, resulting in abnormal peripheral resistance. To examine the hypothesis, we assessed muscle sympathetic nerve activity (MSNA) (microneurography), an indicator of NO release (plasma nitrite/nitrate concentrations) and leg vascular resistance (venous occlusion plethysmography) in 20 healthy male volunteers before and after 14 days of 6 degrees head-down bed rest (HDBR), the ground-based analogue of microgravity. MSNA increased, while plasma nitrite/nitrate concentrations decreased after HDBR. A significant positive correlation observed between MSNA and plasma nitrite/nitrate concentrations before HDBR disappeared after HDBR. Leg vascular resistance increased after HDBR. In conclusion, an imbalance between sympathetic vasoconstrictor traffic and NO release might contribute to elevated peripheral vascular resistance following HDBR.

To examine how long-lasting microgravity simulated by 6 degrees head-down bed rest (HDBR) induces changes in the baroreflex control of muscle sympathetic nerve activity (MSNA) at rest and changes in responses of MSNA to orthostasis, six healthy male volunteers (range 26-42 yr) participated in Valsalva maneuver and head-up tilt (HUT) tests before and after 120 days of HDBR. MSNA was measured directly using a microneurographic technique. After long-term HDBR, resting supine MSNA and heart rate were augmented. The baroreflex slopes for MSNA during Valsalva maneuver (in supine position) and during 60 degrees HUT test, determined by least-squares linear regression analysis, were significantly steeper after than before HDBR, whereas the baroreflex slopes for R-R interval were significantly flatter after HDBR. The increase in MSNA from supine to 60 degrees HUT was not different between before and after HDBR, but mean blood pressure decreased in 60 degrees HUT after HDBR. In conclusion, the baroreflex control of MSNA was augmented, whereas the same reflex control of R-R interval was attenuated after 120 days of HDBR.

To clarify how neural and humoral mechanisms operate to control cardiovascular unctions in man under weightlessness, the response of sympathetic nerve activity was observed in healthy human subjects by means of microneurographic technique with the changes of several hemodynamic parameters and hormonal responses during thermoneutral head-out water immersion. Muscle sympathetic nerve activity was markedly suppressed by head-out immersion, concomitantly with a reduction of the leg volume, an increase of the stroke volume and a reduction of total peripheral resistance. At the same time, plasma level of norepinephrine, vasopressive and antidiuretic hormones (ADH, aldosterone, renin activity, angiotensin I·II) were reduced, while vasodepressive and diuretic hormone (ANP) was markedly increased. The systemic blood pressure was maintained almost unchanged during head-out water immersion. The suppressive response of sympathetic nerve activity seemed to be age-dependent. This response was less prominent in the elderly than in young subjects. It is concluded that the suppressive response of muscle sympathetic activity plays an important role to maintain hemodynamic homeostasis under weightlessness to compensate for the cephalad fluid shift and the resultant increase of the stroke volume in cooperation with the hormonal responses.

We have investigated the changes in muscle sympathetic nerve activity (MSNA) from the tibial nerve during brief periods of microgravity (microG) for approximately 20 s produced by parabolic flight. MSNA was recorded microneurographically from 13 quietly seated human subjects with their knee joints extended in a jet aircraft simultaneously with the electrocardiogram, the blood pressure wave (measured with a Finapres), the respiration curve, and the thoracic fluid volume (measured by impedance plethysmography). During quiet and seated parabolic flight, MSNA was activated in hypergravity and was suppressed in microG phasically. At the entry to hypergravity at 2 G just before microG, the thoracic fluid volume was reduced by 3.2 +/- 3%, and the arterial blood pressure was lowered transiently and then gradually elevated from 89.5 +/- 1.7 to 100.2 +/- 1.7 mmHg, which caused the enhancement of MSNA by 91.4 +/- 14.2%. At the entry to microG, the thoracic fluid volume was increased by 3.4%, which lowered the mean blood pressure to 77.9 +/- 2.3 mmHg and suppressed the MSNA by 17.2%. However, this suppression lasted only approximately 10 s, followed by an enhancement of MSNA that continued for several seconds. We conclude that MSNA is suppressed and then enhanced during microG produced by parabolic flight. These changes in MSNA are in response not only to intrathoracic fluid volume changes but also to arterial blood pressure changes, both of which are caused by body fluid shifts induced by parabolic flight, and these changes are quite phasic and transient.

The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.

To determine whether the baroreflex control of sympathetic nerve activity is attenuated in the elderly, muscle sympathetic nerve activity (MSNA) from the tibial nerve was monitored using microneurography, and heart rate and blood pressure were recorded during the depressor (phase II) or pressor (phase IV) period to Valsalva's maneuver in 10 younger subjects and 7 aged subjects. The baroreflex slope for heart rate showed attenuation in the aged subjects during the pressor phase but not during the depressor phase, the baroreflex slope for MSNA was also attenuated in the aged subjects during the pressor and tended to be attenuated during the depressor phases. These data suggest impaired baroreflex function for both heart rate and sympathetic nerve activity in the elderly.

The sympathetic nervous system plays an important role to maintain the homeostasis of vital functions in humans against environmental stimuli. Sympathetic nerve responses to environmental stimuli in humans have been assessed conventionally using rather indirect methods by analyzing the responses of effector organs or by measuring the changes in plasma norepinephrine level. Meanwhile, the microneurography technique has enabled us to approach the sympathetic nervous system in humans more directly. By applying this technique, it has become possible to investigate how the human sympathetic nervous system responds to different kinds of environmental stimuli. In this paper, the usefulness of microneurography as a research tool in environmental physiology is shown together with a review of microneurographic findings on sympathetic nerve responses to environmental stimuli in humans.

We hypothesized that muscle sympathetic nerve activity (MSNA) and cardiovascular responses to the conventional head-up tilt (HUT) are different from those to head-up suspension (HUS) because of antigravity muscle activity. The MSNA from the tibial nerve, heart rate, blood pressure, stroke volume, cardiac output, and calf blood flow were measured in 13 healthy young subjects. Left atrial diameter was measured by two-dimensional echocardiography in another nine subjects. The resting MSNA and cardiovascular responses at a low level (20°) of orthostasis were similar during both modes. At higher levels (40 and 60°), the responses of MSNA, heart rate, stroke volume, and cardiac output were significantly stronger and there was a smaller reduction in calf blood flow during HUT than during HUS ( P < 0.05). Left atrial diameter was decreased significantly from the resting values during HUT and HUS without any significant difference between the modes of orthostasis. The results provide evidence that the engagement of antigravity muscles during HUT may have additive effects on sympathetic vasoconstrictor and cardiovascular responses to orthostatic stress.

The objective of the present study was to determine the effect of vestibular stimulation on the sympathetic outflow to muscle in humans. Fourteen healthy volunteers were studied while in the supine position with electrocardiography, blood pressure monitoring and electro-oculography. The muscle sympathetic nerve activity (MSNA) was recorded directly from the bilateral tibial nerves by using microneurographic double recording technique. Caloric vestibular stimulation was loaded by alternate irrigation with 50 ml of cold (10 degrees C) water and 50 ml of hot (44 degrees C) water into the left and right external meatus. After cold water irrigation, two MSNA response peaks were elicited, respectively, before and after the maximum slow phase velocity (SPV) of nystagmus. The first peak of the MSNA enhancement was caused by non-specific factors because its time course coincided with that in cold pressor test with immersion of the subject's hand in ice/water (4 degrees C). Transient suppression of MSNA after cold water irrigation in the period of maximum SPV of nystagmus was observed by cross correlogram analysis between the SPV of the nystagmus and MSNA. After hot water irrigation, only one MSNA response peak was elicited after the period of strong nystagmus. The second peak of MSNA enhancement evoked by cold irrigation (379.4 +/- 221.8%, with the control value set as 100%, mean +/- SE) was significantly higher than that evoked by hot irrigation (243.0 +/- 14.5%). The degree of MSNA enhancement by either cold (the second peak) or hot stimulation was proportional to the maximum SPV of the nystagmus. There was no significant difference between the MSNA responses ipsilateral to and contralateral to the irrigated side. In conclusion, the caloric vestibular stimulation can influence the bilateral sympathetic outflow to muscle in humans. The degree of MSNA enhancement is proportional to the magnitude of vestibular excitement indicated by maximum slow phase velocity of the nystagmus.

The aim of this study is to determine the recruitment pattern among individual vasoconstrictor neurons under the baroreceptor-mediated influence in man. Spikes of single vasoconstrictor units were detected from microneurograms with a template-matching method. A total of 39 single vasoconstrictor units were detected. Single vasoconstrictor units were different from each other in their susceptibility to be activated in response to changes in the R-R interval or blood pressure. The units with higher firing probability had a shorter threshold R-R interval and a higher threshold diastolic blood pressure than units with lower firing probability. In sympathetic responses consisting of only one spike (single-spike responses), units with a lower threshold frequently appeared and units with a higher threshold joined mull-spike responses. The units with a short threshold R-R interval tended to have a long inhibitory latency from R wave, suggesting low conduction velocity. The correlation between firing probability and firing threshold and that between appearance in single-spike response and multi-spike response suggest a hierarchical manner of recruitment of vasoconstrictor units. For beat-to-beat responses, however, some deviation from the hierarchical recruitment was also observed.

Saito, Mitsuru, Ryoko Sone, Masao Ikeda, and Tadaaki Mano.Sympathetic outflow to the skeletal muscle in humans increases during prolonged light exercise. J. Appl. Physiol. 82(4): 1237 – 1243, 1997.—To investigate the effects of exercise duration on muscle sympathetic nerve activity (MSNA), heart rate, blood pressure (BP), tympanic temperature, blood lactate concentration, and thigh electromyogram were measured in eight volunteers during 30 min of cycling in the sitting position at an intensity of 40% of maximal oxygen uptake. MSNA burst frequency increased 18 min after exercise was begun (25 ± 4 bursts/min at baseline and 36 ± 5 bursts/min at 21 min of exercise), reaching 41 ± 5 bursts/min at the end of exercise. Heart rate and systolic BP increased during exercise. Twenty minutes after commencement of exercise, however, both systolic and diastolic BP values tended to drop compared with the initial period of exercise. Tympanic temperature increased in a time-dependent manner, and the increment was significant 12 min after exercise was begun. Blood lactate concentration and integrated electromyogram showed no significant changes during exercise. The increased MSNA during prolonged light-intensity exercise may be a secondary effect of the drop in BP as a result of blood redistribution caused by thermoregulation rather than by metaboreflex.

To elucidate the effect of heat stress on the sympathetic nervous system, we evaluated changes in muscle sympathetic nerve activity (MSNA), plasma arginine vasopressin (AVP), tympanic temperature, skin blood flow, cardiac output, mean blood pressure, and heart rate in 9 subjects in response to acute heat stress induced by raising the ambient temperature from 29 to 34 degrees C and then to 40 degrees C. With the heat exposure, MSNA was significantly increased with a significant increase in tympanic temperature. Skin blood flow and heart rate were also significantly increased, while mean blood pressure tended to decline and cardiac output tended to increase. The combination of the increased MSNA and skin blood flow may have caused the redistribution of the circulatory blood volume from the muscles to the skin, facilitating convection heat loss. The increases in MSNA counteracted the lowered blood pressure during heat exposure. Thus, the increased MSNA may play an important role both in thermoregulation and in the maintenance of blood pressure against heat stress.

To determine how the baroreflex control of sympathetic nerve activity is affected by aging, muscle sympathetic nerve activity (MSNA) from the tibial nerve was monitored using microneurography, and heart rate and blood pressure were recorded during the pressor or depressor responses to intravenous injections of phenylephrine or nitroglycerin in 39 healthy humans, aged 16 to 56 years. Although the baroreflex slope for heart rate showed attenuation with aging, the baroreflex slope for MSNA was not affected by aging. These data suggest preservation of the baroreflex control of sympathetic nerve activity despite attenuation of the baroreflex control of parasympathetic nerve activity by aging in humans.

Muscle sympathetic nerve activity (MSNA) is suppressed during thermoneutral head-out water immersion (HOI) in humans. In this study, the effects of ageing on the suppressive response of MSNA to HOI were determined. MSNA was recorded microneurographically from the tibial nerve in 16 healthy men, 10 of whom were aged 19-30 years (young group) and six aged 45-67 years (older group). MSNA was suppressed in all the subjects during HOI. The suppressive response was significantly less prominent in the older group than in the young group. A significant negative correlation between age and the suppressive response of MSNA induced by HOI (r = -0.53, P < 0.05) was found. We conclude that suppressive response of sympathetic nerve activity to HOI is reduced with age.

To analyze how the 1-min oscillation in postural sway and 1-min wave in body fluid volume change contribute to human circulatory homeostasis, several levels of body circumference, foot pressure center, electromyograms, and volumes of the leg, abdomen, and thorax were measured during upright standing for 40 min in 20 healthy young men. Spectral analyses of these parameters revealed that a 1-min rhythm is found in all parameters and that the 1-min wave in body fluid volume changes in the lower leg, which occur in fluid pooling caused by gravity, propagate upward. Muscle pumping in the lower leg triggered by the postural sway was found to increase the power of this 1-min wave. A quantitative analysis of body circumferences disclosed that the 1-min wave in body fluid volume change compensates for gravitational downward fluid shift, with the volume of 6.3 +/- 5.0 ml/cycle at the heart level. We concluded that a coupling mechanism between the 1-min oscillation in postural sway and the upward propagation of 1-min wave in body fluid volume change contributes to maintain systemic blood pressure during upright standing in humans.

The aim of this study was to determine the effect of metoclopramide on the sympathetic nervous system. Muscle sympathetic nerve activity was increased in two stages after metoclopramide injection. The initial increase in sympathetic nerve activity may result from the unloading of arterial baroreceptors because there was a negative correlation between mean blood pressure and muscle sympathetic nerve activity. The later increase in muscle sympathetic nerve activity may be attributed to the central activation of the sympathetic nervous system because there was a positive correlation between mean blood pressure and muscle sympathetic nerve activity. These results suggest that metoclopramide activates the sympathetic nervous system by two different mechanisms.

Background Left stellate ganglion block has been shown to increase heart rate and blood pressure, possible because of blockage of afferent vagal fibers from arterial baroreceptors in the aortic arch. Because efferent muscle sympathetic nerve activity (MSNA) is influenced by the arterial baroreflex, the hypothesis that left stellate ganglion block increases efferent MSNA recorded from the tibial nerve of humans was tested. Methods Twenty healthy male volunteers were sequentially assigned to one of three groups: stellate ganglion block (n = 10), in which 7 ml 1% mepivacaine was injected into the left stellate ganglion; placebo (n = 5), in which 7 ml of saline was injected into the left stellate ganglion; and intramuscular injection (n = 5), in which 7 ml mepivacaine was injected into the left deltoid muscle. Direct intraneural microneurographic recording with a tungsten microelectrode was used to record MSNA in the left tibial nerve. MSNA, heart rate, and blood pressure were recorded before and after injection in all groups. An additional five volunteers were studied with transthoracic echocardiography to examine the effect of stellate ganglion block on preload changes. Results Tibial nerve MSNA increased after mepivacaine injection to the left stellate ganglion but was unchanged after saline injection to the left stellate ganglion or mepivacaine injection into the deltoid muscle. Heart rate increased significantly after the left stellate ganglion block but did not change significantly after saline injection to the left stellate ganglion or after mepivacaine injection to the deltoid muscle. Systemic blood pressure did not change significantly in all groups. Left ventricular end-diastolic area and left ventricular end-diastolic circumference did not change after stellate ganglion block. Conclusions Tibial nerve MSNA increased during left stellate ganglion block with mepivacaine.

The aim of the present study was to clarify the acute effect of alcohol drinking on muscle sympathetic nerve activity and other cardiovascular variables in young healthy human volunteers. Seven volunteers (25.0 ± 4.7 years in age, weighing 59.9 ± 5.9 kg) were instructed to lay down on a bed, and muscle sympathetic nerve activity (MSNA) was microneurographically recorded from the tibial nerve, simultaneously with an electrocardiogram, blood pressure with Finapres® and autosphygmomanometer, cardiac output by impedance cardiography, and skin blood flow by laser Doppler flowmetry. After a 1-h rest, the subjects drank alcohol (0.6 g/kg) and were remained in resting position for 105 min. Blood ethanol levels indicated that they were moderately intoxicated. Heart rate constantly increased until 30 min after the ingestion, and maintained a peak level. MSNA was slightly but significantly suppressed just after the ingestion, and was gradually enhanced until the end of the experiment, showing a significant difference from the control level until 40 min in burst rate and until 25 min in total MSNA after the ingestion. Blood pressure showed an abrupt and transient increase at first, then gradual decrease until 30 min after the ingestion, and maintenance of the resting level until the end of the experiment. Cardiac output showed no constant tendency and no significant differences after the ingestion with wide interindividual variation. Skin blood flow increased 15 min after the ingestion. We conclude that rapidly developing disinhibitory action on medullary cardiovascular center and slowly progressive vasodilative action on peripheral vessels by ethanol contributes to the differential actions on the heart rate control and the peripheral sympathetic outflow to muscles, and configures the three-staged changes in blood pressure.

To clarify the effects of manual acupuncture on the autonomic nervous system, we measured efferent muscle sympathetic nerve activity (MSNA) from the right peroneal nerve while simultaneously recording blood pressure and heart rate both during the resting period and after manual acupuncture applied to the Tsusanli acupoint of the same limb. The needle was rotated intermittently for 30 s at 5-min intervals. MSNA increased transiently with the suppression of heart rate during rotation of the acupuncture needle. No consistent change in blood pressure was found throughout the acupuncture session. After removal of the needle, both the MSNA and heart rate returned to the initial control values, and the mean blood pressure showed an increase over the resting value. MSNA showed a negative correlation with heart rate in four out of five subjects who received acupuncture. These results suggest that the coactivation of cardiac vagal and muscle sympathetic nerves is evoked by the acupuncture maneuver.

The aim of the present study was to determine whether static biceps brachii contraction by handcurling enhances the muscle sympathetic nerve activity (MSNA) in the resting muscle. In six healthy men (age: 19-23 years), we measured MSNA in the tibial nerve microneurographically, with heart rate, blood pressure, biceps electromyogram (EMG), and the intensity of local fatigue sensation in the working muscle. Subjects performed static biceps brachii contraction for 2 min (short exercise) at 30% of maximal voluntary contraction, and then they made fatiguing exercise to exhaustion (long exercise). During the short exercise, the heart rate and mean arterial blood pressure increased significantly (p < 0.05). In the last 30s of the short exercise, the MSNA burst rate and total MSNA increased significantly but integrated EMG did not increase. In long exercise, MSNA burst rate, total MSNA, mean arterial blood pressure, heart rate, EMG activity, and local fatigue sensation increased progressively with advancing exercising time. There was a significant correlation between integrated EMG and total MSNA (r = 0.64, n = 63, p < 0.001), and local fatigue sensation and total MSNA (r = 0.41, n = 63, p < 0.001) during the long exercise. Post-exercise recovery of the MSNA response to static handcurling was more prompt in short exercise than that in long exercise. We conclude that MSNA is enhanced during submaximal static handcurling, and the magnitude of enhancement correlates with EMG activity and subjective fatigue sensation in the biceps brachii, which might be attributed to the stimulation of metaboreceptors in the working muscle.

To characterize the features of sympathetic nerve activity during non-REM sleep, we measured the muscle and skin sympathetic nerve activities (MSNA and SSNA, respectively) using a double recording microneurographic technique. Eight healthy volunteers were monitored by polysomnography (including EEG, EOG, EMG, and ECG) and received acoustic stimuli (880 Hz, 125 ms) during sleep stage 2. The specific discharge properties of MSNA during wakefulness included pulse-synchronicity, short burst duration and a non-responsiveness to arousal stimuli. These were considered to be generated by an inhibitory input from the baroreceptors to the cardiovascular center. In contrast, SSNA lacked pulse-synchronicity, had longer bursts, and was responsive to a variety of stimuli. Burst rates of MSNA and SSNA were reduced during sleep stages 1 and 2 (light sleep) vs. during a wakefulness. Both MSNA and SSNA appeared to be related to spontaneously occurring K-complexes. The baroreflex latency (from the ECG R-wave to the integrated MSNA burst peak) was constant at approximately 1.20 s during sleep, suggesting that pulse-synchronicity was maintained. The MSNA burst evolution time (interval between initiation of the burst and its peak) became longer with a transition to deeper non-REM sleep stages, whereas the SSNA burst evolution times remained constant. K-complexes induced by acoustic stimuli were frequently accompanied by MSNA and/or SSNA. MSNA responded to acoustic stimuli during light sleep, but some bursts lacked a close relation in time to cardiac rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to assess age-related changes in sympathetic nerve activity controlling blood pressure, we recorded muscle sympathetic nerve activity, blood pressure, and heart rate during head-up tilt in 10 healthy elderly (69–75 years) and 16 healthy young (19–23 years) subjects. The elderly had significantly lower responsiveness of muscle sympathetic nerve activity to postural change than did the young subjects. In the elderly, marked rise in blood pressure without increase in muscle sympathetic nerve activity was observed in nearly upright position during head-up tilt, whereas this phenomenon was not observed in the young. We conclude that neural control function of blood pressure during head-up tilt in the elderly differs from that in the young, which may be due to age-related change in baroreflex function. © 1993 Academic Press, Inc.

Normal subjects exerted isometric torque at a rapid rate of contraction with different amplitude targets, and at different rates with a constant target. In the fastest contractions, the agonist triceps and antagonist biceps muscles showed an electromyographic volley characterized by a slow wave with an initial negative and subsequent positive phases. The duration of each phase was relatively constant for different target amplitudes. In the agonist, the area comprised by the negative or positive waveform increased with increasing target amplitude and correlated with the peak of the first time derivative of torque. The relationship of the antagonist volley to the target amplitude varied among subjects both in the area and the interval of the agonist-antagonist volley. With a decreasing contraction rate, the agonist volley decreased in the area in correlation with the peak of the torque derivative, retaining a constant duration, while the antagonist volley disappeared. These results suggest that rapid isometric contractions are controlled by an amplitude-modulated pulse of agonist activation, which is associated with a pulse of antagonist activation, while the pulse of the antagonist activation is variably utilized among subjects.

One of the pathophysiological features in Buerger's disease, i.e. thromboangiitis obliterans (TAO), contains a sympathetic contribution which relates to vasospastic phenomenon. The purpose of this study is to clarify sympathetic mechanisms in TAO. Muscle sympathetic nerve activity (MSA) was recorded using a microneurographic technique in patients suffering from TAO. The cold pressor test (by immersing the hand of the subject into ice cold water) was used as a test to examine the sympathetic responsiveness to local cold stimulus. The basal level of the MSA in the TAO group was lower than that in the control group (control group vs. TAO group: 39.8 +/- 12.8 bursts/min vs. 26.1 +/- 12.1 bursts/min in burst rate, P0.05, 61.8 +/- 8.3 bursts/100 heart beats vs. 39.5 +/- 22.3 bursts/100 heartbeats in burst incidence, P0.05). The responsiveness of MSA to the cold pressor test in the TAO group was higher than that in the control group (TAO group vs. control group: 385 +/- 191% total MSA vs. 198 +/- 156% total MSA, P0.05). We directly demonstrated higher responsiveness of MSA to the local cold stimulus in patients with TAO. This hyperresponsive MSA might contribute to the pathophysiologic feature in TAO.

We recorded skin sympathetic nerve activity (SSNA) microneurographically from the right tibial nerve of a patient with acquired idiopathic generalized anhidrosis (AIGA). The patient did not show any spontaneous sweating or pilocarpine- and nicotine-induced sweat response. Histopathologic examination showed degenerated eccrine glands associated with surrounding inflammatory cellular infiltration. Electrical nerve stimulation produced a two-peak pattern of SSNA reflex discharge representing sudomotor and vasoconstrictor components. The frequency of spontaneous SSNA bursts (burst rate), presumably of a sudomotor nature, at the ambient temperature of 25 °C was significantly higher than in a healthy control subject and was further increased at a temperature of over 38 °C. Thus, sudomotor sympathetic nerve activity is well preserved or even increased in AIGA. We conclude that anhidrosis of AIGA results from the generalized sweat gland dysfunction rather than decreased sympathetic outflow to the skin.

To clarify the effect of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a precursor of norepinephrine (NE), the effect of this drug on microneurographically recorded muscle sympathetic nerve activity (MSA) from the tibial nerve was analyzed in ten healthy male volunteers. A single dose of 600 mg of L-threo-DOPS was orally administered and the effect of this norepinephrine precursor on MSA at resting and at upright standing positions, as well as the MSA responsiveness to head-up tilting was examined by comparing the data obtained after administration of the drug with those obtained under control conditions. The plasma NE levels were determined in two subjects. The results were as follows: (1) resting MSA increased significantly 80 min after administration of L-threo-DOPS and was accompanied by an increase in plasma NE levels; (2) standing MSA when treated with the drug was not significantly different from values obtained under control conditions; and (3) MSA responsiveness to orthostasis was reduced after L-threo-DOPS. We conclude from the activation of MSA by L-threo-DOPS that this drug raised blood pressure not only through an increase in metabolized plasma NE levels, but also through the enhancement of MSA by activation of descending noradrenergic or adrenergic pathways proximal to the recording site of the sympathetic discharge.

We studied the effect of adrenergic blockade on hepatic venous hyperglycemia and the activation of a hepatic glycogenolytic enzyme, phosphorylase-a, in response to cerebral cholinergic activation. Neostigmine was injected into the third cerebral ventricle of bilaterally adrenodemedullectomized (ADMX) rats, while somatostatin and insulin were administered intravenously. Hepatic venous plasma glucose concentrations and hepatic phosphorylase-a activity were measured. Intracerebroventricular injection of neostigmine (5 x 10(-8) mol) caused increases in hepatic venous glucose concentrations and hepatic phosphorylase-a activity. Both of these changes were prevented by intraperitoneal (IB) pretreatment with phentolamine (5 x 10(-7), 1 x 10(-6) mol) without the intervention of insulin secretion, but not by pretreatment with the alpha-adrenoreceptor antagonist phenoxybenzamine (1 x 10(-6) mol), the beta-adrenoreceptor antagonist propranolol (1 x 10(-6) mol), the alpha 1-antagonists prazosin or bunazosin (1 x 10(-6) mol), the alpha 2-antagonist yohimbine (1 x 10(-6) mol), or prazosin (5 x 10(-7) mol) plus yohimbine (5 x 10(-7) mol). These results suggest that phentolamine prevented brain-mediated hepatic glycogenolysis by a mechanism that may not be classified pharmacologically as involving either alpha 1- or alpha 2-receptors.

To clarify the effect of a long-acting selective α 1 -adrenoceptive sympathomimetic agent on sympathetic outflow to muscles (muscle sympathetic activity, MSA) in humans, 5 mg of midodrine hydrochloride was injected intravenously in ten healthy male subjects aged 19–25. Spontaneous MSA was significantly suppressed as well as plasma norepinephrine level without changing heart rate, or systemic blood pressure. The suppression continued for more than 90 min. and this is supposed to be due to negative feedback action on the baroreflex loop. The absence of significant changes in heart rate or systemic blood pressure in healthy subjects suggests that hemodynamic homeostasis is maintained by reducing the MSA in response to a long-acting sympathomimetic agent, like midodrine hydrochloride, which constricts peripheral vessels directly.

To clarify the mechanism of postprandial hypotension (PPH), we made microneurographic analyses of patients with PPH and 10 healthy controls by recording multi‐unit vasoconstrictive impulses of muscle sympathetic nerve activity (MSNA) directly from the tibial nerve fascicles during a glucose tolerance test. Oral intake of 75 grams glucose in 225 ml of water produced significant and prolonged hypotension in all patients and an increase in MSNA in all healthy subjects. Insulin and glucose responses were not significantly correlated with arterial blood pressure reduction. PPH was prevented by an infusion of vasopressin (0.3 U/min) given before glucose intake. These results suggest that PPH is caused by the lack of sympathetic compensation for the systemic hypotensive stress of splanchnic blood pooling that occurs after food ingestion, and that prior treatment with vasopressin reduces the portal venous flow by constricting the splanchnic vessels in patients with PPH. NEUROLOGY 1991;41:712‐715

To compare the responses of remote sympathetic nerves to dynamic and static leg exercises, we recorded sympathetic nerve activity leading to skeletal muscle (MSNA) using a tungsten microelectrode during one-leg cycling at loads of 0, 25, and 50 W and during static leg extension (SLE) at 20% of maximal voluntary contraction. Oxygen uptake (Douglas bag method) and local fatigue sensation (LFS) of the working muscle were measured during cycling and SLE. MSNA decreased from the control value, respectively, by 25, 21, and 12% during cycling at loads of 0, 25, and 50 W. The differences from the control value were significant except during cycling at 50 W. On the contrary, MSNA increased from the control value by 83% during SLE. Oxygen uptake during 25 and 50 W leg cycling was greater than during SLE, whereas LFS was higher during SLE than during leg cycling at any load. The results indicate that the response of muscle sympathetic nerves to exercise does not exclusively reflect whole body metabolism, but is instead related to the local metabolic changes.

The present telescience testbed study was conducted to evaluate the feasibility of physiological experimentation under restricted conditions such as during simulated weightlessness induced by using a water immersion facility, a reduced capacity of laboratory facilities, a delay and desynchronization of communication between investigator and operator, restrictions of different kinds of experiments practiced by only one operator following a limited time line and so on. The three day's experiments were carried out following the same protocols. The operators were changed every day, but was the same the first and the third day. The operators were both medical doctors but not all round experts in the physiological experimentation. The experimental objectives were: 1) ECG changes by changing water immersion levels, 2) blood pressure changes, 3) ultrasonic Echo-cardiographic changes, 4) laser Doppler skin blood flowmetry in a finger, 5) blood sampling to examine blood electrolytic and humoral changes. The effectiveness of the testbed experiment was assessed by evaluating the quality of the obtained data and estimating the friendliness of the operation of the telescience to investigators and operators.

The purpose of this study was to determine if response in muscle sympathetic nerve activity (MSNA) to static muscle contraction alters or not during peripheral chemoreceptor stimulation with hypoxia. MSNA was recorded from the tibial nerve using a microneurographic technique in seven healthy subjects in a sitting position. They performed a static handgrip exercise (SHG) for 2 min under normobaric normoxia and hypobaric hypoxic conditions corresponding to an altitude of 4,000 m (460 mmHg). MSNA represented as burst rate and total sympathetic nerve activity (TSNA) (burst rate X mean burst amplitude) at rest increased by 7.7 bursts/min and by 60%, respectively, compared to those under normoxia. During the exercise, MSNA increased over control values before exercise both under normoxia and hypoxia. TSNA increased during the first and second minute of SHG by 19% (p greater than 0.05) and 35% (p less than 0.05) in normoxia and by 15 (p greater than 0.05) and 34% (p less than 0.05) in hypoxia over the control value, respectively, while the absolute intensity of MSNA during SHG was higher under hypoxia. The response of MSNA to SHG which showed algebraic sums was the same under normoxia and hypoxia, that might relate to consist of afferent pathways independent from carotid chemoreflex.

To test the function of sympathetic vasco-constrictor nerves on blood flow in resting limbs during static muscle contraction, muscle sympathetic nerve activity (MSNA) to the leg muscle was recorded from the tibial nerve microneurographically before, during and after 2 min of static handgrip (SHG). Simultaneously, calf blood flow (CBF) was measured by strain gauge plethysmography. An increase in MSNA, a decrease in CBF and an increase in calf vascular resistance (CVR) in the same resting limb occurred concomitantly during SHG. However, the increase in CVR was blunted in the second minute of handgrip when MSNA was still increasing. The results indicated that the decrease of CBF during SHG reflects the increase in MSNA, while the dissociation between MSNA and CVR at the later period of SHG may be related to metabolic change produced by the vasoconstriction.

Finger blood flow (BF) and skin sympathetic nerve activity (SSA) to the glabrous side of the hand were measured during immersion of the hand in a water bath in which temperature (Tw) was raised every 10 min by steps of 2 degrees C from 35 or 37 to 41 degrees C. The experiments were conducted during the summer in rooms in which ambient temperature was 28-32 degrees C or 35 degrees C. The nine healthy male subjects were wearing summer clothes. Finger BF through vessels located deep in the skin was measured by using laser-Doppler flowmetry (ALF-2100, Advance). With the use of a tungsten microelectrode SSA was recorded directly from the median nerve at the wrist or antecubital fossa of the tested arm. With finger vessels already dilated at Tw of 35 or 37 degrees C, finger BF decreased, with a concomitant increase in the SSA bursts as Tw rose to 39-41 degrees C. We confirmed in one subject that anesthetic blockade of the median nerve at the site proximal, but not distal, to the recording site blocked responses to the step rise in Tw in the SSA bursts and in finger BF. From these results we conclude that, with the subject in a warm state, blood vessels of the finger respond to local heating with vasoconstriction, and this finger vasoconstriction is evoked reflexively, largely through the increased sympathetic outflow to the resistance vessels of the finger.

In a warm environment at ambient temperatures between 25 degrees and 38 degrees C (relative humidity 50%-60%) the relationship between sympathetic activity in cutaneous nerves (SSA) and pulses of sweat expulsion was investigated in five young male subjects. The SSA was recorded from the peroneal nerve using a micro-electrode. Sweat expulsion was identified on the sweat rate records obtained from skin areas on the dorsal side of the foot, for spontaneous sweating and drug-induced sweating, using capacitance hygrometry. Sweat expulsion was always preceded by bursts of SSA with latencies of 2.4-3.0 s. This temporal relationship between bursts of SSA and sweat expulsion was noted not only in various degrees of thermal sweating but also in the sweating evoked by arousal stimuli, or by painful electric stimulation. The amplitude of the sudomotor burst was linearly related to the maximal rate of increase of the corresponding sweat expulsion, the amplitude of the expulsion and the integrated amount of sweat produced for the duration of the expulsion. The results provide direct evidence that sweat expulsion reflects directly centrally-derived sudomotor activity.