Effect of space flight and head-down bedrest on neuroendocrine response to metabolic stress in physically trained subjects

The aim of this study was to evaluate the association of plasma epinephrine (EPI) and norepinephrine (NE) responses to insulin induced hypoglycemia (ITT) 3 weeks before the space flight (SF), on the 5th day of SF, on the 2nd and 16th days after the landing in the first Slovak astronaut, and before and on the 5th day of prolonged subsequent head-down (-6 degrees) bed rest (BR) in 15 military aircraft pilots. Blood samples during the test were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transferred to Earth in special container for hormonal analysis. Insulin hypoglycemia was induced by i.v. administration of 0.1 IU/kg BW insulin (Actrapid HM) in bolus. Insulin administration led to a comparable hypoglycemia in pre-flight, in-flight conditions and before and after bed rest. ITT led to a pronounced increase in EPI levels and moderate increase in NE in pre-flight studies. However, an evidently reduced EPI response was found after insulin administration during SF and during BR. Thus, during the real microgravity in SF and simulated microgravity in BR, insulin-induced hypoglycemia activates the adrenomedullary system to less extent than at conditions of the Earth gravitation. Post-flight changes in EPI and NE levels did not significantly differ from those of pre-flight since SF was relatively short (8 days) and the readaptation to Earth gravitation was fast. It seems, that an increased blood flow in brain might be responsible for the reduced EPI response to insulin. Responses to ITT in physically fit subjects indicate the stimulus specificity of deconditioning effect of 5 days bed rest on stress response. Thus, the data indicate that catecholamine responses to ITT are reduced after exposure to real as well as simulated microgravity.     

Acute plasma volume expansion in the untrained alters the hormonal response to prolonged moderate-intensity exercise.

To investigate the role of an increase in plasma volume (PV), characteristically observed with short-term endurance training, on the endocrine response to prolonged moderate intensity exercise, eight untrained males (VO2 peak = 3.52 +/- 0.12 l x min(-1)) performed 90 min of cycle ergometry at approximately 60% VO2peak both before (CON) and following (PVX) PV expansion. Acute PV expansion, which was accomplished using a solution of Dextran (6%) or Pentispan (10%) (6.7 ml kg(-1)), resulted in a calculated 15.8+/-2.2% increase (p<0.05) in PV. The prolonged exercise resulted in increases (p<0.05) in plasma vasopressin (AVP), plasma rennin activity (PRA), aldosterone (ALD), atrial naturetic peptide (alpha-ANP), and the catecholamines norepinephrine (NE) and epinephrine (EPI). PVX blunted the increases (p<0.05) in AVP, PRA, ALD, NE and EPI, during the exercise itself. The concentration of alpha-ANP was also lower (p<0.05) during exercise following PVX, an effect that could be attributed to the lower resting levels. No differences in osmolality was observed between conditions. These results demonstrate that PVX alters the fluid regulatory hormonal response in untrained subjects to moderate intensity dynamic exercise in a manner similar to that observed following short-term training induced alterations in PV. The specific mechanisms responsible for these alterations remain unclear, but appear to be related directly to the increase in PV.     

Prolonged exercise following diuretic-induced hypohydration effects on fluid and electrolyte hormones.

To investigate the hypothesis that a reduction in plasma volume (PV) induced by diuretic administration would result in an increase in the fluid and electrolyte hormonal response to exercise, ten untrained males (VO(2) peak = 3.96 +/- 0.14 l/min) performed 60 min of cycle ergometry at 61 % VO(2) peak twice. The test was carried out once under control conditions (CON) (placebo) and once after 4 days of diuretic administration (DIU) (Novotriamazide; 100 mg triamterene and 50 mg hydrochlorothiazide). Calculated resting PV decreased by 14.6 +/- 3.3 % (p < 0.05) with DIU. No difference in plasma osmolality was observed between conditions. For the hormones measured, differences (p < 0.05) between conditions at rest were noted for plasma renin activity (PRA) (0.62 +/- 0.09 vs. 5.61 +/- 0.94 ng/ml/h), angiotensin I (ANG 1) (0.26 +/- 0.03 vs. 0.56 +/- 0.08 ng/ml), aldosterone (ALD) (143 +/- 14 vs. 1603 +/- 302 pg/ml), arginine vasopressin (AVP) (4.13 +/- 1.1 vs. 9.58 +/- 1.6 pg/ml) and atrial natriuretic peptide (alpha-ANP) (11.5 +/- 2.8 vs. 6.33 +/- 1.0 pg/ml). The exercise resulted in increases (p < 0.05) in PRA, ANG I, ALD, AVP, alpha-ANP. DIU led to higher levels of PRA, ANG I, and ALD (p < 0.05) and lower levels of alpha-ANP (p < 0.05) compared to CON. Arginine vasopressin was not affected by the loss of PV. For the catecholamines--norepinephrine (NE) and epinephrine (EPI)--only NE was higher during exercise with DIU compared to CON (p < 0.05). For PRA and ALD, the higher levels observed during exercise with DIU could be explained both by higher resting levels and a greater increase during exercise itself. For ANG I and NE, the effect of DIU only manifested itself during exercise. In contrast, the lower alpha-ANP observed during exercise with DIU was due to the lower resting levels. These results support the hypotheses that hypohydration leads to alterations in the secretion of all of the fluid and electrolyte hormones with the exception of AVP. The specific mechanisms of these alterations remain unclear, but appear to be related directly to the decrease in PV.     

Effect of head-down bed rest on the neuroendocrine response to orthostatic stress in physically fit men

The role of neuroendocrine responsiveness in the development of orthostatic intolerance after bed rest was studied in physically fit subjects. Head-down bed-rest (HDBR, -6 degrees, 4 days) was performed in 15 men after 6 weeks of aerobic training. The standing test was performed before, after training and on day 4 of the HDBR. Orthostatic intolerance was observed in one subject before and after training. The blood pressure response after training was enhanced (mean BP increments 18+/-2 vs. 13+/- 2 mm Hg, p<0.05, means +/- S.E.M.), although noradrenaline response was diminished (1.38+/-0.18 vs. 2.76+/-0.25 mol.l(-1), p<0.01). Orthostatic intolerance after HDBR was observed in 10 subjects, the BP response was blunted, and noradrenaline as well as plasma renin activity (PRA) responses were augmented (NA 3.10+/-0.33 mol.l(-1), p<0.001; PRA 2.98+/-1.12 vs. 0.85+/-0.15 ng.ml(-1), p<0.05). Plasma noradrenaline, adrenaline and aldosterone responses in orthostatic intolerant subjects were similar to the tolerant group. We conclude that six weeks of training attenuated the sympathetic response to standing and had no effect on the orthostatic tolerance. In orthostatic intolerance the BP response induced by subsequent HDBR was absent despite an enhanced sympathetic response.     

Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans.

This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and spaceflight.     

Hormonal changes during 17 days of head-down bed-rest

We investigated in six men the impact of 17 days of head-down bed rest (HDBR) on the daily rhythms of the hormones involved in hydroelectrolytic regulation. This HDBR study was designed to mimic a real space flight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of Growth Hormone (GH), Cortisol, 6 Sulfatoxymelatonin, Normetadrenaline (NMN) and Metadrenaline (NM) was determined. A decrease in urinary cortisol excretion during the night of HDBR was noted. For GH, a rhythm was found before and during HDBR. The rhythm of melatonin, evaluated with the urine excretion of 6 Sulfatoxymelatonin (aMT6S), the main hepatic metabolite, persisted throughout the experiment without any modification to the level of phase. A decrease during the night was noted for normetadrenaline urinary derivates, but only during the HDBR.     

Circadian variations in plasma renin activity, catecholamines and aldosterone during exercise in women

Four women were studied at 0400 h and 1600 h to determine if their hormonal and hemodynamic responses to exercise varied with the circadian cycle. Esophageal temperature was measured during rest and exercise (60% peak VO2; 30 min) in a warm room (Ta = 35 degrees C; PH2O = 1.7 kPa). Venous blood samples were drawn during rest and exercise and hemoglobin concentration (Hb), hematocrit (Hct), plasma osmolality (Posm), plasma protein concentration (Pp), colloid osmotic pressure (COP), plasma renin activity (PRA), cortisol, aldosterone, norepinephrine (NE) and epinephrine (E) were determined. Changes in plasma volume (PV) were estimated from changes in Hb and Hct. The relative hemoconcentration (-11.2%) was similar at 0400 h and 1600 h, but the absolute PV was smaller at 1600 h than at 0400 h (p = 0.03). The responses of Posm, Pp and COP to exercise were unaffected by time of day. Although PRA was not different at the two times of day, PRA was 244% greater during exercise at 1600 h, but only 103% greater during exercise at 0400 h. The normal circadian rhythms in plasma aldosterone (p = 0.043) and plasma cortisol (p = 0.004) were observed. Plasma aldosterone was 57% greater during exercise, while plasma cortisol did not change. The change in E and NE was greater at 0400 h, but this was due to the lower resting values of the catecholamines at 0400 h. These data indicate that time of day generally did not affect the hormonal or hemodynamic responses to exercise, with the exception that PRA was markedly higher during exercise at 1600 h compared to 0400 h.     

Fluid volume changes and LBNP response after simulated weightlessness with varied oral sodium supply

There is evidence on body fluid volume effects of head-down tilt bed rest and altered oral sodium supply, but the combined impact of both has not been investigated in detail. We therefore studied circulatory adaptation to 8 days -6 degrees head down bed rest (HDBR) with different levels (-140 to -430 mM/d) of oral sodium load (SL). We expected decreased extracellular volume and increased aldosterone and PRA levels with low sodium load, and hypothesized that these effects get exaggerated with additional HDBR, also influencing lower body suction (LBNP) responses. Variations in sodium status seem to influence plasma but not interstitial volume, confirming recent results of another group who used different experimental conditions.     

Effect of simulated microgravity on endocrine response to insulin-induced hypoglycemia in physically fit men.

Adaptation to microgravity is associated with alteration in some endocrine functions. In the present longitudinal study, the counterregulatory hormonal response to insulin-induced hypoglycemia (ITT, 0.1 IU/kg short acting insulin i. v.) was evaluated under simulated microgravity conditions in 15 physically fit subjects. ITT was performed at the beginning of the investigation, and again after completion of 6 weeks of endurance training and after a subsequent period of 4 days of head-down bed rest at a backward tilt of 6 degrees from the horizontal. Endurance training showed a significant increase in maximal aerobic capacity in previously well-trained subjects (increase by 12 %), as well as on attenuation of counterregulatory response of epinephrine to hypoglycemia. After 4 days of bed rest, basal concentrations of plasma norepinephrine was diminished (p < 0.002) and plasma renin activity was enhanced (p < 0.02). After bed rest, decreased responses of the two catecholamines (norepinephrine, p < 0.001; epinephrine, p < 0.001), growth hormone (p < 0.001), and cortisol (p < 0.05) were observed. Response of plasma renin activity after bed rest was increased (p < 0.01). This longitudinal study indicated that 4 days of bed rest in endurance-trained subjects induced increased response of PRA to hypoglycemia and attenuation of other counterregulatory neuroendocrine responses.     

Plasma catecholamines: effects of footshock level and hormonal modulators of memory storage

Plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured in male Sprague-Dawley rats before and at several times after training injections of agents known to enhance or to impair later retention performance for a one-trial inhibitory (passive) avoidance task. Two days before testing, each animal was surgically prepared with a chronic tail artery catheter that allows for repeated blood sampling in unhandled rats. Exposure to a single, intense training footshock (3.0 mA, 2.0 sec duration) resulted in an immediate but transient increase in plasma levels of EPI and to a lesser extent NE. Plasma levels of both catecholamines did not differ between unshocked controls and animals that received a weak training footshock (0.6 mA, 0.5 sec duration). An injection of EPI at a dose that enhances retention performance (0.1 mg/kg, sc) resulted in increments in plasma EPI levels of 0.8-1.9 ng/ml from 5 to 40 min after injection. An injection of EPI (0.5 mg/kg, sc) at a dose that produces retrograde amnesia resulted in increments in plasma EPI ranging from 3.7 to 4.5 ng/ml during the 40 min after injection. Plasma NE levels were not significantly altered following an EPI injection. A single injection of adrenocorticotropin (ACTH, 0.3 or 3.0 IU per rat) did not alter the plasma catecholamine responses to training with a weak footshock. Similarly, the synthetic ACTH analog, Organon 2766 (125 or 250 mg/Kg) did not affect plasma catecholamines in untrained (unshocked) rats.These results demonstrate that significant increments in plasma levels of NE and EPI occur shortly after inhibitory avoidance training. Furthermore, an injection of EPI that enhances retention of an inhibitory avoidance task mimics the magnitude, though not the temporal characteristics, of the endogenous adrenal medullary response to a training footshock. Other hormonal treatments (ACTH and Organon 2766) which enhance memory storage do not affect plasma levels of NE and EPI.     

Differential plasma catecholamine and neuropeptide Y responses to acute stress in rats

Neuropeptide Y (NPY) is a vasoconstrictor present in the sympatho-adrenomedullary system and may be co-released with norepinephrine (NE) and epinephrine (EPI) during sympathetic activation. We studied plasma NPY-immunoreactivity (-ir, radioimmunoassay) and catecholamine (radioenzymatic) responses during two acute stress paradigms that differ in character, intensity, and duration. The intermittent stress of footshock (0.75 and 1.5 mA, 0.5 sec duration, at 5-sec intervals, for 5 min) evoked intensity-dependent immediate increments in plasma NE and EPI, and a delayed NPY-ir response (+0.6 +/- 0.1 pmol/ml). Prolonged (60 min) immobilization caused greater increases in plasma NE and EPI levels and no changes in plasma NPY-ir until the end of the stress session (+0.3 +/- 0.1 pmol/ml). Plasma NPY-ir responses correlated with those of NE but not with EPI suggesting a sympathetic origin for the release of the peptide. Relatively greater NPY-ir responses to footshock than to immobilization may be consistent with a preferential release of the peptide by a bursting but not continuous mode of sympathetic activation. However, it may also be due to a differential activation of the sympathetic nerves and adrenal medulla by these two stress situations.     

Modification of water and electrolyte metabolism during head-down tilting by hypoglycemia in men.

The effect of hypoglycemic stress on the changes in water and electrolyte metabolism induced by head-down tilting (HDT) was studied. Six healthy men were subjected to postural changes (30 min standing, 2 h HDT, 1 h standing), with or without the intravenous administration of insulin at the beginning of HDT. When insulin was not given, antidiuretic hormone (ADH), cortisol, plasma renin activity (PRA), aldosterone, and catecholamine levels were decreased and atrial natriuretic polypeptide (ANP) levels increased during HDT. These changes were associated with 2.5- and 1.5-fold increases in urine flow and sodium excretion, respectively, when compared with the amounts before HDT. On the other hand, insulin-induced hypoglycemia during HDT produced increases in ADH, cortisol, PRA, aldosterone, and catecholamine levels. At the same time, an exaggerated ANP response by HDT was observed. These hormonal changes were associated with an abolishment of the increases in urine flow and sodium excretion. It is suggested that acute stress modifies the changes in fluid and electrolyte metabolism induced by HDT.     

Leptin responses to physical inactivity induced by simulated weightlessness

Physical inactivity induced by head-down bed rest (HDBR) affects body composition (BC). Leptin is involved in BC regulation by acting on fuel homeostasis. We investigated whether leptin and counterregulatory hormone levels are affected by a 7-day HDBR. Fasting blood was sampled daily (0700) in males (n = 8) and on alternating days in females (n = 8) for measurements of leptin, insulin, norepinephrine (NE), epinephrine (Epi), growth hormone (GH), cortisol, nonesterified fatty acid (NEFA), and glucose. BC was measured by H(2)(18)O dilution. Energy intake (men 10.5 +/- 0.2 MJ/day, women 7.9 +/- 0.3 MJ/day) and BC were unchanged by HDBR. Increased levels of leptin (men 40%, P = 0.003; women 20%, P = 0. 050), insulin (men 34%, P = 0.018; women 25%, P = 0.022), and the insulin-to-glucose ratio (men 30%, P = 0.049; women 25%, P = 0.031) were noted. GH, NE, Epi, and cortisol levels were unaltered. NEFA dropped in both sexes, but glucose decreased only in women. In conclusion, HDBR increased leptin levels independently of stress response, changes in fat mass, energy intake, or gender. These changes were correlated to the insulin-resistance development in men. Further analyses are required, but the results have to be considered for longer HDBR periods with 1) the well-described drop in energy intake and 2) the BC changes.     

Sympathetic nervous activity decreases during head-down bed rest but not during microgravity.

We tested the hypothesis that sympathoadrenal activity in humans is low during spaceflight and that this effect can be simulated by head-down bed rest (HDBR). Platelet norepinephrine and epinephrine were measured as indexes of long-term changes in sympathoadrenal activity. Ten normal healthy subjects were studied before and during HDBR of 2-wk duration, as well as during an ambulatory study period of a similar length. Platelet norepinephrine concentrations (half-life = 2 days) were studied in five cosmonauts, 2 wk before launch, within 12 h after landing after 11-12 days of flight, and at least 2 wk after return to Earth. Because of the long half-life of platelet norepinephrine, data obtained early after landing would still reflect the microgravity state. Platelet norepinephrine decreased markedly during HDBR (P < 0.001), whereas there were no significant changes when subjects were ambulatory. Platelet epinephrine did not change during HDBR. During microgravity, platelet norepinephrine and epinephrine increased in four of the five cosmonauts. Platelet norepinephrine concentrations expressed in percentage of preflight and pre-HDBR values, respectively, were significantly different during microgravity compared with HDBR [153 +/- 28% (mean +/- SE) vs. 60 +/- 6%, P < 0.004]. Corresponding values for platelet epinephrine were also significant (293 +/- 85 vs. 90 +/- 12%, P < 0.01). The mechanism of the platelet norepinephrine and epinephrine response during spaceflight flight is most likely related to the concomitant decrease in plasma volume. HDBR cannot be applied to simulate changes in sympathoadrenal activity during microgravity.     

Alteration of humoral and peripheral vascular responses during graded exercise in heart failure

We hypothesized that performanceof exercise during heart failure (HF) would lead to hypoperfusion ofactive skeletal muscles, causing sympathoactivation at lower workloadsand alteration of the normal hemodynamic and hormonal responses. Wemeasured cardiac output, mean aortic and right atrial pressures,hindlimb and renal blood flow (RBF), arterial plasma norepinephrine(NE), plasma renin activity (PRA), and plasma arginine vasopressin(AVP) in seven dogs during graded treadmill exercises and at rest. Incontrol experiments, sympathetic activation at the higher workloadsresulted in increased cardiac performance that matched the increasedmuscle vascular conductance. There were also increases in NE, PRA, and AVP. Renal vascular conductance decreased during exercise, such thatRBF remained at resting levels. After control experiments, HF wasinduced by rapid ventricular pacing, and the exercise protocols wererepeated. At rest in HF, cardiac performance was significantly depressed and caused lower mean arterial pressure, despite increased HR. Neurohumoral activation was evidenced by renal and hindlimb vasoconstriction and by elevated NE, PRA, and AVP levels, but it didnot increase at the mildest workload. Beyond mild exercise, sympathoactivation increased, accompanied by progressive renal vasoconstriction, a fall in RBF, and very large increases of NE, PRA,and AVP. As exercise intensity increased, peripheral vasoconstriction increased, causing arterial pressure to rise to near normal levels, despite depressed cardiac output. However, combined with redirection ofRBF, this did not correct the perfusion deficit to the hindlimbs. Weconclude that, in dogs with HF, the elevated sympathetic activity observed at rest is not exacerbated by mild exercise. However, withheavier workloads, sympathoactivation begins at lower workloads andbecomes progressively exaggerated at higher workloads, thus alteringdistribution of blood flow.

     

Influence of season on plasma antidiuretic hormone, angiotensin II, aldosterone and plasma renin activity in young volunteers

We investigated seasonal changes in hormonal and thermoregulatory responses. Eight volunteers were subjected to the experiment at four times of the year: around the vernal and autumnal equinoxes, and at the summer and winter solstices at latitude 35° N. Plasma antidiuretic hormone (ADH), angiotensin II (ANG II), aldosterone (ALD) and plasma renin activity (PRA) were analyzed before and after water immersion. Seasonal changes in thermoregulatory responses were assessed by measuring core temperature and sweat rate during immersion of the leg in hot water (at 42°C) for 30 min in a room maintained at 26°C. The concentration of plasma ADH and ALD before water immersion was significantly higher in summer than in other seasons. The concentrations of ANG II and PRA did not show seasonal variations. Changes in tympanic temperature during water immersion showed significant differences between seasons, and were higher in winter than in other seasons. The sweat rate was significantly higher in summer than in other seasons. In summary, ADH and ALD concentrations displayed a seasonal rhythm with marked elevation in summer; this may be a compensative mechanism to prevent dehydration from increased sweat loss during summer due to heat acclimatization.     

Relationship between stroke volume and sympathetic nerve activity: new insights about autonomic mechanisms of syncope

Head-up tilt table experiments conducted in astronauts prior to and immediately after the NASA Neurolab Space Mission (STS-90) revealed that a reduction in stroke volume induced by moving from the supine to upright posture was associated with increased muscle sympathetic nerve activity (MSNA). Although this finding was not unexpected, lower average stroke volume and greater average MSNA measured after space flight in both supine and upright postures were positioned in a linear fashion on the same stroke volume-MSNA stimulus-response relationship as the average pre-flight stroke volume and MSNA responses. Since all astronauts who participated in the Neurolab orthostatic experiments completed the 10-min tilt table tests, these observations supported the notion that sympathetic reflex responses were not altered but functioned adequately after space flight in non-presyncopal subjects. In contrast to the Neurolab results, development of orthostatic hypotension and presyncopal events reported in astronauts during standing after space flight have been accompanied by attenuated peripheral vasoconstriction and less elevation in plasma concentrations of norepinephrine. The association between circulating norepinephrine (NE) and peripheral vascular resistance in presyncopal astronauts after space flight led to the conclusion that postflight presyncope can be attributed to a combination of inherently low-resistance responses, a strong dependence on volume status, and relative hypoadrenergic function. In the present investigation, we used graded levels of lower body negative pressure (LBNP) to produce linear reductions in stroke volume and performed direct measurements of MSNA to test the hypotheses that (1) elevations in MSNA during central hypovolemia are proportional (i.e., linear) with reductions in stroke volume and; (2) that the slope of the stroke volume-MSNA relationship will be reduced in presyncopal subjects.     

Cardiovascular and hormonal responses to swimming and running in the rat

Hemodynamic and hormonal responses were studied during swimming (SW) and running (R) and in cage-confined (C) female Wistar rats at base line and 4 and 8 wk of training. Myocardial tissue levels of norepinephrine (NE) and epinephrine (EPI) were also measured at the end of 8 wk of training. Mean arterial blood pressure (BP), heart rate (HR), and blood samples for arterial lactate, plasma NE and EPI, and blood gases were obtained at rest and at 20, 40, and 60 min of exercise. After 4 wk of SW, a resting bradycardia was observed, and HR response for the remaining 4 wk was attenuated with SW compared with HR during R. BP and blood gases remained unchanged between the two groups. R resulted in increased arterial lactate concentrations compared with C and SW at base line but was not different from SW at 4 wk. SW elicited higher plasma levels of NE and EPI compared with C at base line and C and R at 4 wk. Myocardial tissue NE and EPI concentrations were markedly increased in both the left and right ventricle of the SW group compared with both R and C. These results indicate that BP and blood gases are not different between chronic R and SW and suggest a possible sympathoadrenal role in the differences observed in cardiac adaptations between R and SW.     

Effects of 3-day bed rest on physiological responses to graded exercise in athletes and sedentary men.

To test the hypotheses that short-term bed-rest (BR) deconditioning influences metabolic, cardiorespiratory, and neurohormonal responses to exercise and that these effects depend on the subjects' training status, 12 sedentary men and 10 endurance- and 10 strength-trained athletes were submitted to 3-day BR. Before and after BR they performed incremental exercise test until volitional exhaustion. Respiratory gas exchange and heart rate (HR) were recorded continuously, and stroke volume (SV) was measured at submaximal loads. Blood was taken for lactate concentration ([LA]), epinephrine concentration ([Epi]), norepinephrine concentration ([NE]), plasma renin activity (PRA), human growth hormone concentration ([hGH]), testosterone, and cortisol determination. Reduction of peak oxygen uptake (VO(2 peak)) after BR was greater in the endurance athletes than in the remaining groups (17 vs. 10%). Decrements in VO(2 peak) correlated positively with the initial values (r = 0.73, P < 0.001). Resting and exercise respiratory exchange ratios were increased in athletes. Cardiac output was unchanged by BR in all groups, but exercise HR was increased and SV diminished in the sedentary subjects. The submaximal [LA] and [LA] thresholds were decreased in the endurance athletes from 71 to 60% VO(2 peak) (P < 0.001); they also had an earlier increase in [NE], an attenuated increase in [hGH], and accentuated PRA and cortisol elevations during exercise. These effects were insignificant in the remaining subjects. In conclusion, reduction of exercise performance and modifications in neurohormonal response to exercise after BR depend on the previous level and mode of physical training, being the most pronounced in the endurance athletes.     

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.