Static handgrip exercise modifies arterial baroreflex control of vascular sympathetic outflow in humans.

To examine effects of static exercise on the arterial baroreflex control of vascular sympathetic nerve activity, 22 healthy male volunteers performed 2 min of static handgrip exercise at 30% of maximal voluntary force, followed by postexercise circulatory arrest (PE-CA). Microneurographic recording of muscle sympathetic nerve activity (MSNA) was made with simultaneous recording of arterial pressure (Portapres). The relationship between MSNA and diastolic arterial pressure was calculated for each condition and was defined as the arterial baroreflex function. There was a close relationship between MSNA and diastolic arterial pressure in each subject at rest and during static exercise and PE-CA. The slope of the relationship significantly increased by >300% during static exercise (P < 0.001), and the x-axis intercept (diastolic arterial pressure level) increased by 13 mmHg during exercise (P < 0.001). These alterations in the baroreflex relationship were completely maintained during PE-CA. It is concluded that static handgrip exercise is associated with a resetting of the operating range and an increase in the reflex gain of the arterial barorelex control of MSNA.

Interrelations of vasoconstrictor sympathetic outflow to skin core temperature during unilateral sole heating in humans.

The purpose of the present study was to clarify how skin sympathetic nerve activity (SSNA) influences the core temperature during local heating of the unilateral sole of the foot for 60 min. We recorded SSNA microneurographically from the tibial or peroneal nerve simultaneously with skin blood flow, sweat rate at heated and non-heated sites, with tympanic temperature (Tty) as the core temperature. Sole heating began to suppress vasoconstrictive SSNA (vasoconstrictor) after 3.4 +/- 1.1 min, decrease Tty after 7.4 +/- 2.0 min, activate vasoconstrictor after 33.4 +/- 2.2 min, and increase Tty after 45.5 +/- 2.7 min. Regarding the interaction between vasoconstrictor and Tty during sole heating, we found the following: (1) the capability to suppress vasoconstrictors (decrease rate) showed positive correlations with the time delay from vasoconstrictor suppression to the Tty decrease (r = 0.752, p < 0.05), and with the Tty decrease rate (r = 0.795, p < 0.05), (2) the Tty decrease rate was inversely related to the capability to activate vasoconstrictors (increase rate) (r= -0.836, p < 0.05), and (3) the capability to activate vasoconstrictors was inversely related to the time delay from vasoconstrictor activation to the Tty increase (r = -0.856, p < 0.05) and showed a positive correlation with the Tty increase rate (r = 0.819, p < 0.05). These significant correlations indicate that the capability to control vasoconstrictors to the skin is one of the determinant factors maintaining core temperature in human thermoregulatory function. In conclusion, human thermoregulatory function is largely dependent on the suppression and activation capability of vasoconstrictors.

Influence of vestibulo-sympathetic reflex on muscle sympathetic outflow during head-down tilt.

To clarify the response of muscle sympathetic nerve activity (MSNA) to static stimulation of otolith organs in a craniocaudal direction (+Gz) in humans, we examined the effect of otolith stimulation on MSNA without changing the effect of cardiopulmonary baroreceptors using a 6-8.5 degrees head-down tilt (HDT) and lower body negative pressure (LBNP) device. Before the study, we established that 6-8.5 degrees HDT with 10 mmHg LBNP caused a fluid shift to the degree that the thoracic impedance was the same as the supine position without LBNP. Subjects were young male volunteers aged 22.1 +/- 3.8 years who gave informed consent. MSNA was recorded from the tibial nerve by microneurography simultaneously with heart rate (ECG), thoracic fluid volume (impedance method), and blood pressure (tonometric method). During 6-8.5 degrees HDT with 10 mmHg LBNP, MSNA was suppressed slightly without significantly changing heart rate, thoracic impedance, or mean arterial blood pressure. The results suggest that the sympathosuppression was related not to the result of cardiopulmonary [correction of cardioplumonary] loading but to the -Gz change (caudocranial direction [correction of dirction]) of 0.1 G. It is estimated that the vestibulo-sympathetic reflex may suppress sympathetic outflow to muscles in humans.

Effect of simulated microgravity exposure on thermoregulatory control of sweating.

The purpose of the present study was to investigate the alterations in thermoregulatory control following 14 days of head-down bed rest (HDBR). The threshold temperature for sweating onset and sweating sensitivity were determined from sweating rates on the chest and forearm, and tympanic temperature as an index of core temperature (Tc) in nine healthy males exposed to a 60-min heat stress with a water-perfused blanket before and after HDBR. The threshold temperature for sweating onset, that is, the Tc at which sweating began on the chest and forearm was 36.75 +/- 0.14 and 36.72 +/- 0.13 degrees C before HDBR, respectively. The value significantly increased to 37.05 +/- 0.09 (p<0.05) for the chest and 37.04 +/- 0.08 degrees C (p<0.05) for the forearm after HDBR. On the other hand, the sweating sensitivity which was indicated as a slope of the Tc-sweating rate relationship significantly decreased from 4.20 +/- 1.15 to 2.32 +/- 1.18 for the chest (p<0.05) and from 4.20 +/- 1.06 to 2.92 +/- 0.98 mg/min/cm2/degrees C for the forearm (p<0.05) after HDBR. These findings suggest that the heat-dissipatory function was attenuated after 14 days of HDBR.

Head-down bed rest alters sympathetic and cardiovascular responses to mental stress.

Astronauts usually work under much mental stress. However, it is unclear how and whether or not an exposure to microgravity affects physiological response to mental stress in humans. To examine effects of microgravity on vasomotor sympathetic and peripheral vasodilator responses to mental stress, we performed 10 min of mental arithmetic (MA) before and after 14 days of 6 degrees head-down bed rest (HDBR), a ground-based simulation of spaceflight. Total muscle sympathetic nerve activity (MSNA, measured by microneurography) slightly increased during MA before HDBR, and this increase was augmented after HDBR. Calf blood flow (measured by venous occlusion plethysmography) increased and calf vascular resistance (calculated by dividing mean blood pressure by calf blood flow) decreased during MA before HDBR, but these responses were abolished after HDBR. Increases in heart rate and mean blood pressure during MA were not different between before and after HDBR. These findings suggest that HDBR augmented vasomotor sympathoexcitation but attenuated vasodilatation in the calf muscle in response to mental stress.

Increased vasomotor sympathetic nerve activity and decreased plasma nitric oxide release after head-down bed rest in humans: disappearance of correlation between vasoconstrictor and vasodilator.

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.

Arm elevation enhances muscle sympathetic nerve activity during static exercise.

The purpose of the present study was to evaluate the effect of hypoperfusion to the static-exercised-muscle induced by arm elevation on muscle sympathetic nerve activity (MSNA) recorded from the right tibial nerve (n= 10) by microneurography. Subjects performed static handgrip exercises (SHG) at 30% of maximal voluntary contraction (MVC) for 2 min, followed by 2 min of posthandgrip muscle ischemia (PHGMI) at the heart level (control) and with the arm elevated (50 cm above heart level). Basal heart rate, mean blood pressure and MSNA responses expressed as burst rate (bursts/min) and total MSNA (%) were unaffected by the arm-position. Heart rate response during SHG was not influenced by the arm elevation, while mean blood pressure and MSNA responses were increased by it (P<0.05). MSNA responses were increased during the second minute of the SHG period (P<0.05) and the PHGMI period (P<0.05) in the elevated arm position. In conclusion, arm elevation increased MSNA responses to SHG and PHGMI, suggesting an increased magnitude of muscle metaboreflex.

Muscle sympathetic nerve activity (MSNA) during high-intensity, isometric leg exercise in humans.

Muscle sympathetic nerve activity (MSNA) is activated during mild-intensity isometric handgrip exercise, but not during isometric leg exercise at a similarly relative intensity. It is unclear whether MSNA is increased by leg exercise at heavy intensity in humans. We aimed to examine how MSNA responds to high-intensity, isometric leg exercise in humans. Eight young healthy male volunteers performed isometric plantar flexions of high intensity (70% of MVC) for 2 min, followed by 2 min of post-exercise muscle ischemia (PEMI; isolated muscle metaboreflex stimulation), with monitoring of muscle sympathetic nerve activity (MSNA), heart rate and arterial blood pressure. MSNA was increased at the onset of exercise (p<0.05), and further increased to 512 +/- 111% of baseline at the second min of exercise (p<0.05). Furthermore, MSNA remained elevated above baseline during PEMI (259 +/- 41 % of baseline, p<0.05). Heart rate also rose at the onset of the test (P<0.05) and gradually increased all through the test (p<0.05), but decreased to baseline level during PEMI. Mean blood pressure was progressively increased from the onset to the end of test (p<0.05), and remained elevated above baseline during PEMI (p<0.05). In summary, MSNA was increased progressively throughout high-intensity, isometric plantar flexion in humans, primarily due to muscle metaboreflex.

Innervation zones of the upper and lower limb muscles estimated by using multichannel surface EMG.

The distribution of innervation zones was investigated in 3 subjects for 17 muscles and 8 muscle groups in the upper and lower limb, by detecting bi-directional propagation of motor unit action potentials (MUAPs) with the multichannel surface electrode array. Clarification of the distribution of innervation zones depended on the ease in detecting the propagation of MUAPs and the actual scattering of innervation zones, which were closely related with muscle morphology with respect to the arrangements of muscle fibers. In muscles having fibers running parallel to each other, such as the biceps brachii, intrinsic hand muscles, vastus lateralis and medialis, tensor fasciae latae, peronei, soleus, tibialis anterior, and hypothenar muscles in the foot, it was relatively easy to detect the propagating MUAPs, and the innervation zones were distributed in a relatively narrow band around muscle belly. On the other hand, in muscles with a complicated structure including pinnation of muscle fibers, in-series muscle fibers and aponeurotic tissues, such as the deltoid, flexors and extensors in the forearm, rectus femoris, sartorius, hamstrings and gastrocnemius, it was more difficult to detect the propagating MUAPs and to identify the innervation zones, which were widely scattered or distributed in complex configurations. The distribution of the innervation zones clarified in the present study can be used to find the optimal location of electrodes in surface EMG recordings and of stimulus electrodes in the functional and therapeutic electrical stimulations. It may also be useful in motor point biopsy for diagnosis of neuromuscular diseases as well as in the botulinum toxin injection for the treatment of spasticity.

Body temperature and skin blood flow during a 14-day bed-rest in a head-down tilt position in humans.

Exposure to microgravity or simulated microgravity is known to affect regulatory function in autonomic nervous system. With regard to thermoregulation, simulated microgravity impairs sweating and induces lower skin and higher internal temperatures during physical work. During supine rest after HDT bed rest, the internal temperatures were reported to be higher than those of pre-HDT bed rest in some studies but not in others. There is no report about the dynamic changes of skin blood flow during 14-day HDT bed rest. The process of HDT bed-rest deconditioning on the function of the thermoregulatory system is virtually unknown. The HDT induces an immediate cephalad fluid shift which would inhibit the sympathetic outflow through the arterial and cardiopulmonary baroreflexes, which may increase the skin blood flow. On the other hand, prolonged HDT bed rest induces dehydration, which will increase sympathetic outflow through cardiopulmonary baroreceptor modulation. Both sympathetic activation and dehydration itself will decrease skin blood flow. It seems probable that the general effect on skin blood flow may reverse along the HDT bed rest. However, the dynamic characters of skin blood flow and body temperature during the HDT bed rest have not been studied thoroughly. Therefore, the purpose of present study was to investigate the changes of skin blood flow and body temperature during 14 days HDT bed rest.

Arterial baroreflex control of sympathetic vasoconstrictor traffic and orthostatic intolerance after head-down bed rest.

The purpose of the present study is to examine the changes in the arterial baroreflex control of muscle sympathetic nerve activity (MSNA) after head-down bed rest (HDBR), in relation to orthostatic hypotension after HDBR. Therefore, we performed 60 degrees head-up tilt (HUT) tests before and after 14 days of HDBR, with monitoring MSNA, heart rate and blood pressure. We calculated the gain of the arterial baroreflex control of MSNA, and compared the gains between the subjects who did (defined as the fainters) and those who did not (defined as the nonfainters) become presyncopal in HUT tests after HDBR.

Responses of muscle sympathetic nerve activity to static handgrip exercise after 14 days of exposure to simulated microgravity.

Decrease in muscle perfusion affects on cardiovascular response to exercise. Muscle hypoperfusion enhances the increase in blood pressure responses to exercise. Muscle perfusion depends not only on central blood pressure but also how fit the active muscle is above or below the heart level; muscle perfusion decreases as arm is elevated. Static exercise increases muscle sympathetic nerve activity (MSNA) innervating vessels in non-active muscles. The exercise-induced increase in MSNA is mainly mediated by stimulating chemosensitive muscle afferents in active muscles. However, the effect of arm elevation on MSNA during forearm exercise is not examined. On the other hand, space flight and simulated microgravity exposure causes reduction in muscle blood flow, suggesting chronic muscle hypoperfused condition during simulated microgravity. Therefore, there is a possibility that arm elevation after microgravity exposure alters MSNA responsiveness during exercise. However, arm elevation effect after exposure to simulated microgravity is not examined.

Effects of leg venous hemodynamics on cardiovascular responses to lower body negative pressure and aging.

In aged people, decreases in stroke volume and cardiac output during orthostatic challenge are less. It is suggested that the stiffness of blood vessels is greater in the elderly, blunting leg venous pooling and drop in central blood volume in an upright position. Leg venous hemodynamics plays an important role in human cardiovascular homeostasis against gravitational stress. This study aimed to clarify how aging influences the leg venous hemodynamics and its contribution to cardiovascular homeostasis during lower body negative pressure (LBNP) in humans.

Regulation of the venous capacitance during microgravity.

The purpose of this paper is to report our recent investigations on the relationship between sympathetic tone and leg venous compliance, as well as on the baroreflex control of leg venous compliance after simulated microgravity exposure in healthy humans.

Leg venous compliance in orthostatic intolerance before and after 14-day head-down bed rest.

To test the hypothesis that increased leg venous compliance (LVC) is one of the contributory factors to orthostatic intolerance (OI) after simulated microgravity, 28 healthy young males were exposed to a 14-day head-down bed rest, and LVC was measured by venous occlusion plethysmography. Orthostatic tolerance was evaluated by a 60 degree head-up tilt (HUT) for 15 min. Sixteen subjects suffered from OI after the bed rest. They were then divided into orthostatic tolerance (non-fainters, n=12) and intolerance (fainters, n=16) groups. We found that fainters had significantly larger LVC before bed rest (0.055 +/- 0.003 vs. 0.065 +/- 0.002 ml 100 ml-1 mm Hg-1, non-fainter vs. fainter; P < 0.05). After bed rest, LVC markedly increased in both groups. In all the subjects calf circumference was reduced on average by 4.7% and the percent change in LVC was negatively correlated with the percent change in calf circumference when all subjects' data were combined after bed rest (r = -0.42, P < 0.05). Our results did not support the hypothesis that increased LVC is the contributory factor to OI after a 14-day bed rest; however, the mechanisms behind the large LVC in the fainters before bed rest are unclear, and the initial LVC might be a predictive indicator for OI after microgravity exposure.

Effects of aging on leg vein filling and venous compliance during low levels of lower body negative pressure in humans.

To evaluate the fluid shift and leg venous compliance during orthostatic stress with advancing age, 12 aged and 5 young healthy males were subjected to graded lower body negative pressures (LBNP) of -5, -10, and -15 mmHg. Cardiovascular variables were monitored continuously, and leg venous compliance was determined by venous occlusion plethysmography. Neither heart rate nor mean arterial pressure changed significantly in any subject during LBNP. A progressive decrease in the thoracic fluid volume index and a gradual increase in the leg fluid volume index, indicating a fluid shift towards the lower body were observed significantly in the young group (p<0.05), while these changes were not significant in the aged group. A linear reduction in peripheral venous pressure could be seen during graded LBNP in all subjects, but the reduction rate was smaller in the aged group. Baseline leg venous compliance was reduced in the elderly (p<0.05). During LBNP, venous compliance decreased in all subjects, but the decrease was significantly smaller in the aged group (p<0.05). It is suggested that the smaller fluid shift and smaller decreased leg venous compliance in aged people during gravitational stress were mainly due to the vascular and ventricular stiffness induced by an age-related reduction in visco-elasticity of the peripheral venous and ventricular walls.

Sympathetic vasoconstriction and orthostatic intolerance after simulated microgravity.

Upon a return to the earth from spaceflight, astronauts often become presyncope during standing. This orthostatic intolerance is provoked by the exposure to the stimulation model of microgravitational environment in humans, 6 degrees head-down bed rest (HDBR). The mechanism for the orthostatic hypotension after microgravity remains unclear. It has been reported that a microgravity-induced loss of circulatory blood volume, a withdrawal of vagal tone, or a reduction of carotid-cardiac baroreflex function may relate to this phenomenon. A recent article has reported that astronauts who showed presyncopal events after spaceflight had subnormal increases in plasma norepinephrine under the standing tests, suggesting that a hypoadrenergic responsiveness to orthostatic stress may partly contribute to postflight orthostatic hypotension. However, it is unclear how and whether or not the sympathetic outflow to peripheral vessels and the release of norepinephrine from sympathetic nerve terminals were altered after microgravity. The vasomotor sympathetic outflow to the skeletal muscle can be directly recorded as muscle sympathetic nerve activity (MSNA) using a microneurographic technique. In addition, the rate of an increase in plasma norepinephrine per that in MSNA in response to applied orthostatic stress can partly indicate the norepinephrine release to sympathetic stimuli as a trial assessment. Therefore, we performed 60 degrees head-up tilt (HUT) tests before and after 14 days of HDBR, and examined the differences in the MSNA response and the indicated norepinephrine release during HUT tests between the subjects who did (defined as the fainters) and those who did not (defined as the nonfainters) become presyncopal in HUT tests after HDBR.

Vasomotor sympathetic nerve responses to static handgrip after simulated microgravity.

During the isometric exercise, the autonomic nervous system has a major role in the regulation of arterial blood pressure, blood flow, and perfusion to the active skeletal muscle in humans. An increase in cardiac sympathetic nerve activity and a withdrawal of vagal tone cause elevations of heart rate, cardiac contractility and cardiac output. An increase in vasomotor sympathetic nerve activity causes a vascular constriction to redirect the oxygen transport to the contracting muscle. It has been reported that the autonomic and cardiovascular systems are commonly affected by the exposure to the real (i.e. spaceflight) and simulated microgravitational environment( i.e. 6 degrees head-down bed rest (HDBR)). The alteration in the autonomic system includes a reduced vagal tone, and an attenuated carotid-cardiac baroreflex function. It may also include an altered control of peripheral vessels, a reduced sympathetic vasoconstriction, an attenuated release of norepinephrine from sympathetic nerve terminal, an impaired myogenic contractility, an up- or down regulation of alpha-adrenergic receptors, and an attenuated multiple vasodilatation. Therefore, there seems to be a possibility that HDBR alters the sympathetic and cardiovascular responses to isometric exercise in humans, however, this possibility has not been examined efficiently. We compared the vasomotor sympathetic and cardiovascular responses to sustained handgrip (HG) until fatigue followed by post-exercise muscle ischemia (PEMI) after 14 days of HDBR, to those before HDBR, in 16 healthy males.