An innovative in vitro device providing continuous low doses of γ-rays mimicking exposure to the space environment: A dosimetric study.

Astronauts are exposed to microgravity and chronic irradiation but experimental conditions combining these two factors are difficult to reproduce on earth. We have created an experimental device able to combine chronic irradiation and altered gravity that may be used for cell cultures or plant models in a ground based facility. Irradiation was provided by thorium nitrate powder, conditioned so as to constitute a sealed source that could be placed in an incubator. Cell plates or plant seedlings could be placed in direct contact with the source or at various distances above it. Moreover, a random positioning machine (RPM) could be positioned on the source to simulate microgravity. The activity of the source was established using the Bateman formula. The spectrum of the source, calculated according to the natural decrease of radioactivity and the gamma spectrometry, showed very good adequacy. The experimental fluence was close to the theoretical fluence evaluation, attesting its uniform distribution. A Monte Carlo model of the irradiation device was processed by GATE code. Dosimetry was performed with radiophotoluminescent dosimeters exposed for one month at different locations (x and y axes) in various cell culture conditions. Using the RPM placed on the source, we reached a mean absorbed dose of gamma rays of (0.33 ± 0.17) mSv per day. In conclusion, we have elaborated an innovative device allowing chronic radiation exposure to be combined with altered gravity. Given the limited access to the International Space Station, this device could be useful to researchers interested in the field of space biology.

Pain and Vertebral Dysfunction in Dry Immersion: A Model of Microgravity Simulation Different from Bed Rest Studies.

BACKGROUND: Astronauts frequently experience back pain during and after spaceflight. The aim of this study was to utilize clinical methods to identify potential vertebral somatic dysfunction (VD) in subjects exposed to dry immersion (DI), a model of microgravity simulation. METHOD: The experiment was performed in a space research clinic, respecting all the ethical rules, with subjects completing three days of dry immersion (n = 11). Assessments of VD, spine height, and back pain were made before and after simulated microgravity. RESULTS: Back pain was present in DI with great global discomfort during the entire protocol. A low positive correlation was found (Pearson r = 0.44; P < 0.001) between VD before DI and pain developed in the DI experiment. CONCLUSIONS: There is a specific location of pain in both models of simulation. Our analysis leads to relativizing constraints on musculoskeletal system in function of simulation models. This study was the first to examine manual palpation of the spine in a space experience. Additionally, osteopathic view may be used to select those individuals who have less risk of developing back pain.

The cardiovascular effects of salidroside in the Goto-Kakizaki diabetic rat model.

Many factors, including hyperglycemia, hypertension, obesity, dyslipidemia, and a sedentary lifestyle, contribute to a high prevalence of cardiovascular disease. Specific vascular impairment treatments in the context of diabetes and vascular risk need to be improved. Salidroside is the primary active component of Rhodiola rosea and has documented antioxidative, cardioprotective, and vasculoprotective properties. The aim of this study was to test the hypothesis that salidroside has protective effects against hyperglycemia, hypertension, and vasodilation impairment in the Goto-Kakizaki (GK) rat model of diabetes. We evaluated cardiovascular parameters (e.g., daytime/nighttime systolic and diastolic blood pressure, heart rate, and activity), metabolic parameters (e.g., body weight, food and water consumption, serum fructosamine level, glucose tolerance), eNOS / phospho-eNOS expression level and in vitro vascular reactivity of aorta and second-order mesenteric arteries in Wistar-Kyoto (control) and GK (diabetic) rats treated with salidroside (40 mg/kg) or placebo (water) for 5 weeks. GK rats showed hypertension, marked glucose intolerance, and impaired endothelium-dependent and endothelium-independent vasodilation capacity. Salidroside showed beneficial effects on endothelial and non-endothelial vasodilation and likely acts on the endothelium and smooth muscle cells through the soluble guanylyl cyclase pathway. Despite its vascular effects, salidroside had no effect on blood pressure and heart rate in GK and control rats, it did not improve glucose metabolism or limit hypertension in the GK model of type 2 diabetes.

Energy and water metabolism, body composition, and hormonal changes induced by 42 days of enforced inactivity and simulated weightlessness.

Inactivity causes profound deleterious changes. We investigated in eight healthy men the impact of a 42-day head-down bed rest (HDBR) on energy and water metabolism and their interrelationships with body composition (BC) and catabolic and anabolic hormones. Total energy expenditure (TEE), total body water, water turnover, and metabolic water formation were assessed by the doubly labeled water method 15 days before and for the last 15 days of HDBR. Resting energy expenditure was determined by indirect calorimetry, and BC was determined by dual energy x-ray absorptiometry. Urinary excretion of cortisol, GH, normetanephrine, metanephrine, urea, and creatinine were measured daily. HDBR resulted in significant reductions in body weight (2%), total body water (5%), metabolic water (17%), and lean body mass (LBM; 4%), but fat mass and water turnover did not change. Segmental BC showed a decreased LBM in legs and trunk, whereas fat mass increased, no significant changes were noted in the arms. The hydration of LBM was unchanged. TEE and energy intake decreased significantly (20% and 13%), whereas resting energy expenditure was maintained. Expenditure for physical activity dropped by 39%. Subjects were in energy balance during HDBR, whereas it was negative during the control period (-1.5 MJ/day). There were decreases in urinary normetanephrine (23%) and metanephrine (23%), but urinary cortisol (28%; weeks 2 and 3), GH (75%; weeks 2-4), and urea (15%; weeks 3 and 4) increased. It was concluded that during prolonged HDBR no relevant modifications in water metabolism were triggered. BC changes occurred in the nonexercised body segments, and the reduction in TEE was due to inactivity, not to LBM loss. Moreover, body weight alone does not accurately reflect the subject's energy state, and energy balance alone could not explain the body weight loss, which involves a transient metabolic stress.

Presence of atrial natriuretic peptide in two desert rodents: comparison with rat.

Atrial natriuretic peptide (ANP) was characterized and assayed in plasmas, hearts, and brains of two Algerian desert rodents, Psammomys obesus and Meriones libycus along with vasopressin, which was assayed in hypophyses and hypothalami. Using reverse-phase high-performance liquid chromatography and radioimmunoassay, we showed, in plasmas and hearts of both species of desert rats, the presence of peptides similar to rat N- and C-terminal ANP but in lower amounts than in Wistar rats. Conversely, C-terminal ANP was abundantly detected in hypophyses from Meriones libycus rats. As these peptides, through their diuretic and natriuretic activities, are involved in body fluid regulation and electrolyte balance, the reduction of ANP stores in both plasmas and hearts suggests that diuresis and natriuresis are lowered in both species of mammals adapted to arid environments. This could occur because of the vasopressin-mediated adaptation, but also in response to the low ANP involvement in hydro-osmotic regulations, even in Psammomys, which has a dietary salt loading. On the other hand, the higher C-terminal ANP contents in the hypophysis of Meriones than in Psammomys and Wistar rats remain to be understood.

Tissue norepinephrine turnover and cardiovascular responses during intermittent dehydration in the rat.

We investigated the central and peripheral sympathetic responses to intermittent dehydration in rats. The norepinephrine (NE) turnover, a biochemical index correlated with noradrenergic neuronal activity, was measured. The modification of blood pressure was also determined by telemetry during the different cycles of dehydration. Dehydration caused a decrease of NE turnover in A2, A5 and A6 nuclei and in peripheral organs. The vasopressinergic level of dehydrated rats decreased in hypophysis and hypothalamus, and increased in plasma. A repeated gradual increase of arterial blood pressure during the first three days of dehydration, followed by a sudden drop when the rats were rehydrated on the fourth day was observed. In conclusion, our study revealed an increase in blood pressure and in central sympathetic activity during dehydration.

Adaptations to a 7-day head-down bed rest with thigh cuffs.

PURPOSE: Thigh cuffs were two elastic strips fixed at the upper part of each thigh, which limits the shift of fluid from the legs into the cardio-thoracic region. The purpose of this study was to examine the effects of thigh cuffs on hormonal and plasma volume responses and orthostatic tolerance during a 7-day head-down bed rest (HDBR). METHODS: Orthostatic tolerance, plasma volume, total body water, blood volume-regulating hormones, and hydro-electrolyte responses were measured in eight healthy men (age range, 25-40 yr), using thigh cuffs 10 h daily during 7 d of -6 degrees HDBR. RESULTS: Thigh cuffs worn during HDBR attenuated the decrease in plasma volume observed after HDBR (thigh cuffs: -5.85 +/- 0.95% vs control: -9.09 +/- 0.82%, P < or = 0.05). During this experiment, there was no significant change in total body water. Thus, the hypovolemia did not result from a loss of water but from a fluid shift from the blood compartment into the interstitial and/or intracellular compartment. Hormonal responses during HDBR and stand test were not modified by the thigh cuffs. Thigh cuffs had no significant effect on the clinical symptoms of orthostatic intolerance after HDBR. CONCLUSIONS: Thigh cuffs worn during HDBR blunted the decrease in plasma volume but did not reduce orthostatic intolerance; thus, they are not a completely effective countermeasure. Furthermore, hypovolemia seems to be necessary but not sufficient to induce orthostatic intolerance after HDBR.

Effect of a 14-day hindlimb suspension on beta-adrenoreceptors in rats.

Exposure to long-term simulated microgravity exhibits reduced sympathetic nervous system activity. This study tested the hypothesis that the hypersensitivity of adrenoreceptors would explain partly many other features of the hemodynamic consequences of return from space. The biochemical properties of the beta adrenoreceptors (betaAR) were determined using 125I-cyanopindolol (125I-CYP) binding in three rat groups: (1) The first experimental group consisted of 24 h-restrained orthostatic rats in the horizontal position, to test the early effect of the attachment to the suspension device; (2) the second experimental group consisted of 24 h-restrained antiorthostatic rats, to test the early effect of the suspension; (3) the third experimental group consisted of 14 day-restrained antiorthostatic rats, to test the long term effect of the suspension. The study was performed in two organs involved in blood pressure regulation, i.e. the heart (atria and ventricles were separated) and kidneys. The Scatchard analysis of 125I-cyanopindolol binding in both organs indicated no significant alterations in the dissociation constant (Kd) and the maximum binding capacity (Bmax) in the three experimental groups. These results do not allow the conclusion about the SNS adaptation pattern to simulated microgravity. Thus, the hypothesis that betaAR are involved in the cardiovascular adaptation to simulated microgravity is not verified in this model where, as a matter of fact, cardiovascular deconditioning is not verified even if this model is widely used.

Hormonal changes during a 20-week confinement.

BACKGROUND: When the European Space Agency planned the EUROMIR'95 long-duration flight with a European astronaut on board the Russian orbital MIR station, it organized simultaneously a ground simulation, called the Human Behaviour Study, of this manned space mission. The ground simulation was a confinement experiment, and this paper describes the changes in volume-regulating hormones that occurred during and after 20 weeks of confinement. METHODS: In a normobaric diving chamber, 3 subjects were confined for 135 d. Arterial pressure, plasma concentrations of blood volume-regulating hormones (active renin and arginine-vasopressin), and urinary variables (aldosterone, arginine-vasopressin, and metabolites of catecholamines) were measured before, during, and after confinement. RESULTS: Arterial pressure was increased from week 1 until week 15 of confinement, while heart rate was elevated from week 6 until the end of the simulation. Plasma active renin was elevated throughout the confinement (after week 6). Urine volume increased transitively on the first 2 d of confinement. CONCLUSIONS: The results obtained during this long-term confinement experiment have major importance regarding concerns about spaceflight and bed rest data, because we observed hormonal changes during the experiment that normally are assigned to the fluid shift that occurs in weightlessness or in the head-down tilt position (i.e., an increase of renin, an increase of urinary volume during the first two days, and a decreased urinary cyclic guanosine monophosphate.

Orthostatic tolerance and hormonal changes in women during 120 days of head-down bed rest.

BACKGROUND: Women will be included as mission specialists in the upcoming International Space Station program. This paper describes the changes in volume-regulating hormones and determines the degree of degradation in orthostatic tolerance in a group of women after 120 d of bed rest. The aim of this study was to test a countermeasure program to be used by women during long-duration spaceflights. METHODS: For 120 d of -6 degrees head-down bed rest (HDBR), eight healthy women were assigned either to a no-countermeasure (No-CM, n = 4), or to a countermeasure (CM, n = 4) group. In the countermeasure group, exercise began after 2 wk, pharmacological agents were given during the 1st and 3rd mo, and the "Centaur" suit was worn on the last day of bed rest and during the day time for several days after bed rest. Diet supplements were taken during the 1st and 4th mo of HDBR. Tilt tests were run before and after HDBR. RESULTS: After the HDBR, none of the CM subjects, had pre-syncopal or syncopal symptoms during tilt tests: BP was well maintained in the CM group, while heart rate and BP changed in the No-CM group. In plasma, atrial natriuretic peptide (ANP) increased in both groups and remained high throughout HDBR, while aldosterone increased and remained elevated in the No-CM group. Natriuresis was decreased during HDBR. CONCLUSION: The CM protocols used during this study were efficient and prevented orthostatic intolerance for the four CM subjects. It would be necessary to obtain more data regarding this set of CM protocols on female subjects to lead to statistical and formal conclusions.

Cardiovascular deconditioning: From autonomic nervous system to microvascular dysfunctions.

Weightlessness induces an acute syndrome called the cardiovascular deconditioning, associating orthostatic intolerance with syncope, increase in resting heart rate and decrease in physical capability. Orthostatic intolerance occurs after short term and long term head down bed rest and after long term space flight. Both head down bed rest and space flight induce a significant decrease of the spontaneous baroreflex sensitivity. However, spontaneous baroreflex sensitivity only characterizes the cardiac baroreflex loop. To go further with the analysis of cardiovascular deconditioning we were interested in the microcirculation. As the endothelium plays a crucial role in the regulation of vascular homeostasis and local blood flow, we hypothesized that endothelial dysfunction is associated with bed rest induced changes. We investigated endothelial properties before and after 56 days of bed rest in 8 women of control group and in 8 women who regularly performed physical exercise as countermeasure. Our study shows that prolonged bed rest causes impairment of endothelium-dependent functions at the microcirculation level, along with an increase in circulating endothelial cells. Endothelium should be a target for countermeasures during periods of prolonged bed rest or exposure to weightlessness.

Effects of acute and chronic starvation on central and peripheral noradrenaline turnover, blood pressure and heart rate in the rat.

When faced with stress, an organism calls upon several mechanisms to maintain biological homeostasis. The cardiovascular system is the first to respond usually with an increase in arterial pressure and tachycardia. Therefore we investigated the central and peripheral sympathetic responses to acute and chronic starvation in Wistar rats. The noradrenaline (NA) turnover rate was determined in different catecholaminergic nuclei (A1, A2, A5, A6) as well as the arterial blood pressure and heart rate modifications. During acute starvation (3 days of starvation), the NA turnover was increased in the A1 and rostral A2 nuclei as well as in ventricles and kidneys and decreased in the A6 nucleus. During chronic starvation (4 consecutive cycles of 3 days of starvation plus 1 day of feeding), the NA turnover was increased in the A5 and caudal A2 nuclei as well as in ventricles and atria and decreased in the A1 nucleus and kidneys. The arterial blood pressure revealed a gradual decrease during the first 3 days of fasting but the heart rate was not modified. We conclude that starvation should be considered as an unusual state of stress because of the absence of locus coeruleus response (A6 nucleus) despite its well-defined role in stress reactions. One of the manifestations of these central and peripheral noradrenergic changes is the change in blood pressure during the starvation-feeding cycles.

Regional blood flow in conscious rats after head-down suspension.

Exposure to microgravity in humans causes cardiovascular deconditioning affecting blood pressure, heart rate and vascular responsiveness. This study investigated cardiac output, arterial blood pressure and regional blood flows [radioactive microspheres: 57Co, 15.5 (SEM 0.1) microm in diameter] in conscious and freely moving rats subjected to 14 days of simulated microgravity (head-down suspension, HDS) in male Wistar rats: control (horizontally attached, n = 7), suspended for 14 days (n = 8) and suspended/allowed to recover for 10 min (R10min, n = 5) or 24 h (n = 9). Compared to the control group, 14 days of HDS resulted in reduced total peripheral resistance (37%); an increased cardiac index (65%) was associated with no significant change in the mean arterial pressure BPa. There were elevated brain (63%), visceral (> 20%), hindlimb (> 80%) and forelimb (> 215%) muscle blood flows. In the R10min group, the BPa decreased (18%) and the regional blood flows returned to control values. Within 24 h the BPa as well as cardiac index and total peripheral resistance were restored. In conclusion, 14 days of HDS engendered local circulatory changes resulting in transient blood pressure instability during recovery.

Hormonal response to restraint in rhesus monkeys.

The purpose of this study was to characterize the hormonal responses to a restraining system in four adult male rhesus monkeys (Macaca mulatta) in preparation for a spaceflight project. After the monkeys were accustomed to food and water (Phase I), blood-volume-regulating hormones were measured during three phases: 10 days in a metabolic cage (Phase II), 16 days sitting in a restrained position in a specially designed metabolism chair (Phase III) and 10 days in metabolic cage (Phase IV). An increase of active renin (30%) and vasopressin (25%) was observed at the end of Phase III. A decrease of atrial natriuretic peptide (ANP), urodilatin, and sodium excretion occurred during the first days of Phase III. Catecholamines were unchanged. A dramatic increase (tenfold) in urinary excretion of growth hormone occurred during all of Phase III and at the beginning of Phase IV. These findings are similar to those found in man during isolation inactivity and during confinement stress.

Hormonal changes during long-term isolation.

Confinement and inactivity induce considerable psychological and physiological modifications through social and sensory deprivation. The aim of the SFINCSS-99 experiment was to determine the cardiovascular and hormonal pattern of blood volume regulation during long-term isolation and confinement. Simulation experiments were performed in pressurized chambers similar in size to the volumes of modern space vehicles. Group I consisted of four Russian male volunteers, who spent 240 days in a 100-m(3 )chamber. Group II included four males (one German and three Russians) who spent 110 days in isolation (200-m(3) module). The blood samples, taken before, during and after the isolation period, were used to determine haematocrit (Ht), growth hormone (GH), active renin, aldosterone, and osmolality levels. From the urine samples, electrolytes, osmolality, nitrites, nitrates, cortisol, antidiuretic hormone (ADH), aldosterone, normetanephrine and metanephrine levels were determined. The increase in plasma volume (PV) that is associated with a tendency for a decrease in plasma active renin is likely to be due to decreased sympathetic activity, and concords with the changes in urinary catecholamine levels during confinement. Urinary catecholamine levels were significantly higher during the recovery period than during confinement. This suggests that the sympathoadrenal system was activated, and concords with the increase in heart rate. Vascular resistance is determined by not only the vasoconstrictor but also vasodilator systems. The ratio of nitrite/nitrate in urine, as an indicator of nitric oxide release, did not reveal any significant changes. Analysis of data suggests that the duration of the isolation was a main factor involved in the regulation of hormones.

Hormonal regulation during a 60-day confinement (ESA-EXEMSI'92) in humans.

EXEMSI'92 was a 60-day isolation and confinement experiment with an international crew. During this second experiment of the European Space Agency (the first one was a 28-day confinement with 6 men: ISEMSI'90), blood volume regulating hormones and water balance were studied. During ISEMSI'90, stress level was elevated as shown by specific markers and we observed some interesting results which have been already observed before, during bed-rest experiments. Thus, our conclusion was that some of the physiological effects observed during bed rest could be the consequence of the "confinement effect" and/or stress imposed to the subjects during such experiments. The aim of the present physiological study was: 1/to define the origin of the blood pressure increase seen during ISEMSI'90; 2/ to study the blood volume regulating hormones (ANP, renin, aldosterone) variations; 3/ to determine the dehydration level by measuring the total body water with the doubly labeled water (DLW) method and fluid balance in general.

Changes in the sympathetic nervous system induced by 42 days of head-down bed rest.

Changes in autonomic nervous system activity could be linked to the orthostatic intolerance (OI) that individuals suffer after a spaceflight or head-down bed rest (HDBR). We examined this possibility by assessing the sympathetic nervous system activity during 42 days of HDBR in seven healthy men. Heart rate variability was studied with the use of power spectral analysis, which provided indicators of the sympathetic (SNSi) and parasympathetic (PNSi) nervous system influences on the heart. Urinary catecholamines and the spontaneous baroreflex sensitivity were measured. Urinary catecholamines decreased by 21.3%, showing a decrease in SNSi. Heart rate variability was greatly reduced during 42 days of HDBR with a drop in PNSi but with no significant changes in SNSi. The baroreflex sensitivity was greatly reduced (30.7%) on day 42 of HDBR. These results suggest a dissociation between the catecholamine response and the SNSi of the heart rate. This dissociation could be the consequence of an increase in beta-adrenergic receptor density and/or activity induced by a decrease in catecholamines during HDBR. The subjects who suffered from OI also had a greater sympathetic response and much lower baroreflex sensitivity when supine than those who finished the stand test. However, the mean response of all subjects indicated that the sympathetic activity (catecholamine excretion) was probably slightly inhibited during HDBR and could contribute to OI.

Effects of a 60-day confinement on the blood pressure, hormonal responses and body fluids of a mixed crew.

During the EXEMSI experiment, an international crew of 4 subjects (1 woman and 3 men) was confined for 60 days in a normobaric diving chamber (with 1060 mbar atmospheric pressure) to simulate life in a space station and to assess the effects of confinement on psychological and physiological factors. Blood pressure and blood volume regulating hormones (atrial natriuretic peptide, renin, aldosterone) and urine data (24-h urine outputs, ionogram) were measured before (BDC: baseline data collection), during (D: day) and after (R: recovery) confinement. We also measured energy expenditure and total body water, 14 days before, and after 27 days of confinement, by the double-labeled water method. We found a marked increase in 24-h urine output during most of the confinement in the men and the woman. Body weight (-1.8 +/- 0.9 kg) and energy expenditure (-1064 +/- 143 kcal/d, p<0.01) decreased in the 3 men. The total body water (TBW) decreased by 1.5 +/- 1.2 l in the men. Stress was not indicated by plasma and urine catecholamines but plasma growth hormone was elevated on D2 (p<0.01 vs. BDC) in the men. This study shows that confinement conditions can modify body fluid (increases in 24-h urine outputs and TBW changes) and energetic metabolisms.

Cardiovascular responses to orthostatic tests after a 42-day head-down bed-rest.

Cardiovascular responses to orthostatic tests were studied before and after a prolonged 42 day-head-down bed-rest (HDBR;-6 degrees) experiment simulating a long duration space flight. Seven men participating in the experiment underwent stand tests (10 min) and lower body negative pressure (LBNP) tests (5 min at -25, -35, -45 mmHg). Heart rate variability and spontaneous baroreflex response slope (SBS) were analysed to assess autonomic nervous system responses. Changes in plasma volume (PV) were assessed at the end of HDBR. At the end of HDBR, four subjects could not complete the stand tests and one could not complete the LBNP test. A higher stressed heart rate with standing (+ 44% before and + 57% after HDBR) and LBNP exposure (+ 19% before and + 34% after HDBR) were observed. A decrease in blood pressure (BP) reflecting a reduced vasomotor response was only observed with standing (mean BP + 21% before and -8% after HDBR); LBNP was less sensitive probably because it was performed 6 h after the stand test. The PV decreased by 10.6%. A decline in spectrum total power reflecting a reduced variance of RR-interval, a decrease in parasympathetic activity and an increase in sympathetic one were observed at the end of HDBR. The reduced parasympathetic indicator and SBS would suggest that the vagal nerve component of the cardiovascular control had been diminished. Except for a lower BP when standing after HDBR, no significant difference was observed between finishers and non-finishers. Autonomic nervous system changes including reduced vasomotor responses constituted important contributors to the orthostatic intolerance observed here and after space flights. Some autonomic and PV changes seemed to be opposite to those observed with training and would suggest a role of reduced physical activity in cardiovascular changes induced by HDBR.

Influence of head-down bed rest on the circadian rhythms of hormones and electrolytes involved in hydroelectrolytic regulation.

We investigated in six men the impact of a 17-day head-down bed rest (HDBR) on the circadian rhythms of the hormones and electrolytes involved in hydroelectrolytic regulation. This HDBR study was designed to mimic an actual spaceflight. Urine samples were collected at each voiding before, during and after HDBR. Urinary excretion of aldosterone, arginine vasopressin (AVP), cyclic guanosine monophosphate (cGMP), cortisol, electrolytes (Na+ and K+) and creatinine were determined. HDBR resulted in a significant reduction of body mass (P < 0.01) and of caloric intake [mean (SEM) 2,778 (37) kcal.24 h(-1) to 2,450 (36) kcal.24 h(-1), where 1 kcal.h(-1) = 1.163 J.s(-1); P< 0.01]. There was a significant increase in diastolic blood pressure [71.8 (0.7) mmHg vs 75.6 (0.91) mmHg], with no significant changes in either systolic blood pressure or heart rate. The nocturnal hormonal decrease of aldosterone was clearly evident only before and after HDBR, but the day/night difference did not appear during HDBR. The rhythm of K+ excretion was unchanged during HDBR, whereas for Na+ excretion, a large decrease was shown during the night as compared to the day. The circadian rhythm of cortisol persisted. These data suggest that exposure to a 17-day HDBR could induce an exaggeration of the amplitude of the Na+ rhythm and abolition of the aldosterone rhythm.