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Alteration of vasoreactivity of mesenteric arteries in rats after two-week simulated weightlessness.

To investigate the effects of simulated weightlessness on vasoreactivity of mesenteric arteries, rats were tail-suspended for two weeks, and vasoreactivity were studied in vitro using isolated mesenteric arterial ring. The results showed that maximal contractile responses to KCl (10-80 mmol/L) and phenylephrine (PE, 10(-10)-10(-4) mol/L) were attenuated in arterial rings isolated from tail-suspended rats. After constriction caused by 10(-7) mol/L PE, maximal dilatory responses induced by sodium nitroprusside (SNP, 10(-10)-10(-4) mol/L) were not different between tail-suspended and control groups. These data indicated that contractile ability of mesenteric artery was diminished by tail-suspension, whereas the dilatory capacity of arterial smooth muscle was not altered.

Animals↗

[Effects of simulated weightlessness on ultrastructure of soleus muscle spindle in rats].

OBJECTIVE: To study changes in ultrastructure of soleus muscle spindle induced by simulated weightlessness in rats. METHOD: Weightlessness was simulated by tail suspension in female rats. The ultrastructure of isolated soleus muscle spindle were observed in 4 d, 7 d, 14 d tail-suspended and 14 d recovered rats. RESULT: Chaotic myofibril, hyperplasia of mitochondria, and enlargement of terminal cisterna were found in the ultrastructure of isolated soleus muscle spindle in 4 d tail-suspended rats. The ultrastructure of isolated soleus muscle spindle in 7 d tail-suspended rats showed more distinct changes, while that in 14 d tail-suspended rats showed obvious retrograde changes. The ultrastructure of isolated muscle spindle in 14 d recovered rats after 14 d tail-suspension were similar to that of control group. CONCLUSION: Simulated weightlessness could induce time-related and reversible changes in ultrastructure of soleus muscle spindle in rats.

Animals↗

[Vasoconstrictor responsiveness of rat basilar artery enhanced by simulated weightlessness].

OBJECTIVE: To investigate the effects of simulated weightlessness on contractile responsiveness of the basilar artery. METHODS: Rats were subjected to tail-suspension for 4-wk to simulate the effect of weightlessness, responses of perfused isolated basilar arterial rings to various vasoactive compounds were examined. RESULTS: Maximal isometric contractile responses to KCl [ (10~100) mmol/L], arginine vasopressin [AVP, (10(-15)~10(-7) mol/L], or 5-hydroxytryptamine [5-HT, (10(-12) ~ 10(-4) mol/ L] were significantly enhanced in arterial rings isolated from 4-wk tail-suspended as compared with that from simultaneous control rats. CONCLUSION: These results indicate that medium-term simulated weightlessness may result in an enhanced contractile responsiveness in rat basilar artery, and strongly support the hypothesis of cerebrovascular syncope-initiating mechanism.

Aerospace Medicine↗

[Study on mechanisms of T lymphocyte function changes in mice under simulated weightlessness in terms of IL-2 and Bcl-2 gene transcription].

To understand the mechanisms of T lymphocyte function changes under simulated weightlessness T lymphocyte proliferation (MTT assay), IL-2 production (biological assay), IL-2 gene (dot blot) and Bcl-2 oncogene (RT-PCR) transcription of splenic cell were observed in mice. The results showed that on the 7 th and 14 th day of simulated weightlessness T lymphocyte proliferation and IL-2 production decreased and significant on the 14 th day; on the 7 th and 14 th day of simulated weightlessness IL-2 and Bcl-2 gene transcription decreased, significant on the 14 day. It demonstrated that simulated weightlessness inhibits IL-2 production by decreasing IL-2 gene transcrition. IL-2 and Bcl-2 gene may be regulators of lymphocyte function under simulated weightlessness.

Animals↗

Simulated weightlessness alters the nycthemeral distribution of energy expenditure in rats.

The energy metabolism adaptations to simulated weightlessness in rats by hindlimb tail suspension are unknown. 12 male rats were assigned to 7 days of isolation, 7 days of habituation to the suspension device, 10 days of simulated weightlessness, and 3 days of recovery. The 24-hour energy expenditure was measured by continuous indirect calorimetry. We calculated the 12-hour energy expenditure during the active (night) and inactive (day) periods, the minimal observed metabolic rates with the day values taken as an index of the basal metabolic rate, and the non-basal energy expenditure representing the cost of physical activity plus the diet-induced thermogenesis. Suspension did not change the mean 24-hour energy expenditure (360.8+/-15.3 J min(-1) kg(-0.67)), but reduced the night/day difference by 64 % (P<0.05) through a concomitant drop in night-energy expenditure and increase in day values. The difference between night and day minimal metabolic rates was reduced by 81 % (P<0.05), and the transient rise in day values suggests an early and moderate basal metabolic rate increase (9 %). An overall 19 % reduction in non-basal energy expenditure was observed during simulated weightlessness (P<0.05), which was mainly attributable to a reduction in the cost of physical activity. 3 days of recovery restored the night/day differences but increased the 24-hour energy expenditure by 10 % (P<0.05). In conclusion, hindlimb tail suspension in rats did not alter the 24-hour energy expenditure, but it transiently increased the basal metabolic rate, and altered both the energy expended on physical activity and the nycthemeral distribution of motor activity. These data suggest that the circadian rhythms of energy expenditure are affected during simulated weightlessness.

Animals↗

Sympathetic nervous adjustments in man to simulated weightlessness induced by water immersion.

To clarify the role of the sympathetic nervous system to adjust the fluid shift under weightlessness, muscle and skin sympathetic activities were recorded microneurographically in human subjects under simulated weightlessness induced by water immersion up to the levels of the knee, the navel, the breast and the neck. The muscle and skin sympathetic activities were reduced in proportion to rise of immersion level up to the neck. These changes of sympathetic activities were almost concomitant with those of simultaneously recorded soleus electromyograms and heart rate. Reductions of the thigh and the leg circumference were also confirmed by strain gauge plethysmogram recorded under the same experimental condition. Based on these findings, it is concluded that the sympathetic nervous system is suppressed under weightlessness simulated by water immersion. This suppression might depend mainly on the activation of intrathoracic low pressure receptors, due to the fluid shift toward the upper part of the body. The suppression of the sympathetic nervous system seems to be important to compensate the fluid shift under weightlessness.

Adult↗

[Effects of simulated weightlessness on the hypophyseal-cortical-adrenal axis in the pregnant rat].

The eventual part of stress in the hormonal responses to simulated weightlessness was studied during gestation in the rat. We have compared these responses with the effects of two other situations well-known to provoke stress: ultrasounds and denutrition. An increase of blood and adrenal corticosterone levels was found in mothers after denutrition, neither after ultrasounds nor after simulated weightlessness. In foetuses, a decrease of weight was noted after denutrition and simulated weightlessness. Foetal suprarenal corticosterone remained normal when mothers were submitted to simulated weightlessness. In this group, a decrease in foetal weight was found that could be explained by non suprarenal hormonal factors or by circulation disturbances.

Animals↗

Effect of simulated weightlessness on phase II drug metabolism in the rat.

BACKGROUND: Exposure to weightlessness is known to alter physiological processes in humans and animals. As a result of these changes, hepatic drug metabolism may be altered as well. Indeed, short term simulated weightlessness in the rat has been shown to increase oxidative metabolism. HYPOTHESIS: Simulated weightlessness will increase Phase II drug metabolism in the rat during short-term tail suspension. METHODS: The tail-suspended rat model was used to simulate weightlessness. Rats were subjected to 1, 3, 7, or 10 d of tail-suspension in order to mimic the effect of exposure to a microgravity environment. One additional rat group was not suspended and served as a control. On the final day of the study, rats we administered a single intravenous bolus dose of acetaminophen 25 mg x kg(-1) through an implanted jugular catheter and serial blood samples were taken for 90 min. Serum acetaminophen concentrations were measured by high-performance liquid chromatography. Pharmacokinetic parameters were determined by using standard model independent methods. RESULTS: The results show that simulated weightlessness in the rat has no effect on Phase II drug metabolism, using acetaminophen as a marker compound. CONCLUSIONS: These data support the hypothesis that simulated weightlessness in the rat modulates oxidative metabolism, but not drug conjugation to glucuronide or sulfate metabolites. These data offer insight into the physiological changes and variability seen in hepatic metabolic profiles in humans and animals following actual spaceflight.

Acetaminophen↗

[Effects of simulated weightlessness on T cell subpopulations and activity of IL-2 and IL-6 in mice].

OBJECTIVE: To observe the effects of simulated weightlessness on the immunogenic activities in mice. METHOD: T cell subpopulations and the activity of IL-2 and IL-6 were observed in mice after exposure to head-down (-30 degrees) tail suspension for 3 d and 7 d. RESULT: The activity of IL-2 and IL-6 in mice showed no change after simulated weightlessness for 3 d compared with the control group. But after simulated weightlessness for 7 d, CD3+ and CD4+ were markedly reduced (both P< 0.01) and CD8+ and CD4+/CD8+ also tended to decrease; the activity of IL-2 was significantly decreased, while the activity of IL-6 tended to increase. CONCLUSION: Simulated weightlessness for 7 d had significant effects on T cell subpopulations and the activity of certain cytokines in mice.

Animals↗

Effects of simulated weightlessness on the release of PGE2 in rat calvarial osteoblasts induced by flow shear stress.

OBJECTIVE: To observe the effects of simulated weightlessness on the release of prostaglandin E2 in rat calvarial osteoblasts by flow shear stress (FSS). METHOD: Osteoblasts were isolated from neonatal rat calvariae and then were set to two groups. One was cultured in 1 G terrestrial gravitational environment. The other was cultured on a clinostat (simulating weightlessness environment) for 60 h, then the osteoblasts were treated with 0.5 Pa or 1.5 Pa FSS in a flow chamber for 1 h. Then release of PGE2 in the osteoblasts was determined. RESULT: 0.5 Pa and 1.5 Pa FSS treatments significantly increased the release of PGE2 in osteoblasts cultured in 1 G environment (P < 0.01) , but there was no remarkable difference between the responses of 0.5 Pa FSS treatment group and 1.5 Pa group (P > 0.05). By contrast, in cells cultured in simulated weightlessness environment, no detectable release of PGE2 was found with the treatment of 0.5 Pa FSS (P < 0.01). The release of PGE2 was delayed and the amount of PGE2 Production was remarkably decreased with 1.5 Pa FSS treatment (P < 0.01). CONCLUSION: These results demonstrated that the responsiveness of osteoblasts to FSS was down-regulated in simulated weightlessness.

Animals↗

Altered cytochrome P450 and P-glycoprotein levels in rats during simulated weightlessness.

BACKGROUND: In order to investigate the effects of simulated weightlessness on drug metabolism, liver, kidney, and small intestine, microsomal proteins from tail-suspended rats were analyzed to determine cytochrome P450 (CYP) and P-glycoprotein levels following varying durations of tail-suspension. HYPOTHESIS: P-glycoprotein and CYP levels would both decrease similar to previous findings from actual spaceflight data. METHODS: Six groups of four Sprague-Dawley rats each were tail-suspended for up to 21 d; CYP and P-glycoprotein levels in the liver, kidney and small intestine were then measured by Western blotting. The results were compared with a control group of unsuspended rats. RESULTS: Our data showed there were significant changes in the levels of hepatic CYP2C11, 2E1, 4A1, and P-glycoprotein and significant changes in the levels of P-glycoprotein and CYP4A1 in the kidney. However, there were no significant changes detected in the levels of CYP3A2 in the liver or small intestine. CONCLUSIONS: We conclude that simulated weightlessness, using the tail-suspended rat model, showed significant suppressive effects on levels of CYP2C11, 2E1, and P-glycoprotein in the liver and CYP4A1 in the kidney, while demonstrating no significant effect on the levels of CYP3A2 in the liver or small intestine. Thus, generalized predictions on the effect of simulated microgravity on drug metabolism cannot be made and the overall effect of spaceflight on individual enzymes should be investigated.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Erythrocyte deformation in simulated weightless human and rabbits.

Effect and mechanism of simulated weightlessness (SWL) in humans and rabbits erythrocyte deformation were studied. Erythrocyte deformation and membrane fluidity in humans and rabbits, and erythrocyte morphology and hemorreology indices in control and HDT rabbits were measured. The results were a decrease in erythrocyte deformation and membrane fluidity in humans and rabbits during SWL, a significant increase in abnormal erythrocyte, blood viscosity, hematocrit, fibrinogen, and red blood cell aggregation index in HDT rabbits. These results show that the changes in erythrocyte shape, increase of erythrocyte internal viscosity and changes in erythrocyte visco-elasticity may be causing the decrease of erythrocyte deformation in SWL humans and rabbits.

Adolescent↗

[Effect of simulated weightlessness on the apoptosis of thymus cells in tail-suspended mice].

OBJECTIVE: To investigate the effect of simulated weightlessness on apoptosis of thymus cells in mice. METHOD: Tail-suspended mice were used as an animal model of simulated weightlessness; chromosome breakage was measured by PI staining, and changes of cell membrane were determined by Annexin-V analysis. RESULT: As compared with the control, there was no obvious chromosome breakage; the total number of apoptotic cells and number of early apoptotic cells increased in 1 d suspended group; the number of early apoptotic cells increased significantly and the total number of apoptotic cells increased very significantly in 2d suspended groups. CONCLUSION: These results suggested that simulated weightlessness could promote apoptosis of thymus cells.

Animals↗

[Effects of simulated weightlessness on vasoreactivity of hindlimb arterial bed in rats].

OBJECTIVE: To investigate the alterations in vasoreactivity of hindlimb arterial bed after simulated weightlessness. METHOD: The tail-suspended rat model was used to simulate weightlessness, and the alterations in vasoreactivity of arterial bed were examined in vitro using isolated, constant flow perfused hindlimb of 2-wk suspended rats and control rats. RESULT: Perfusion flow-pressure relationship of hindlimb arterial bed showed no significant differences between suspended rats and control rats; but vascular responses to KCl (20-100 mM) and PE(10(-8)-10(-4) M) were decreased in hindlimb arterial bed of suspended rats as compared with that of control rats. CONCLUSION: Contractile ability of resistance vessels was diminished in simulated weightlessness rats, and a compromised ability of resistance vessels to increase peripheral resistance may play an important role in occurrence of orthostatic intolerance.

Adaptation, Physiological↗

An optimized index of human cardiovascular adaptation to simulated weightlessness.

Prolonged exposure to weightlessness is known to produce a variety of cardiovascular changes, some of which may influence the astronaut's performance during a mission. In order to find a reliable indicator of cardiovascular adaptation to weightlessness, we analyzed data from nine male subjects after a 24-hour period of normal activity and after a period of simulated weightlessness produced by two hours in a launch position followed by 20 hours of 6 degrees head-down tilt plus pharmacologically induced diuresis (furosemide). Heart rate, arterial pressure, thoracic fluid index, and radial flow were analyzed. Autoregressive spectral estimation and decomposition were used to obtain the spectral components of each variable from the subjects in the supine position during pre- and post-simulated weightlessness. We found a significant decrease in heart rate power and an increase in thoracic fluid index power in the high frequency region (0.2-0.45 Hz) and significant increases in radial flow and arterial pressure powers in the low frequency region (<0.2 Hz) in response to simulated weightlessness. However, due to the variability among subjects, any single variable appeared limited as a dependable index of cardiovascular adaptation to weightlessness. The backward elimination algorithm was then used to select the best discriminatory features from these spectral components. Fisher's linear discriminant and Bayes' quadratic discriminant were used to combine the selected features to obtain an optimal index of adaptation to simulated weightlessness. Results showed that both techniques provided improved discriminant performance over any single variable and thus have the potential for use as an index to track adaptation and prescribe countermeasures to the effects of weightlessness.

Adaptation, Physiological↗

Plasma viscosity elevations with simulated weightlessness.

Bed rest studies which simulate weightlessness have demonstrated marked changes in the state of hydration of subjects as well as decrements in aerobic capacity. These two phenomena may be linked through increases in blood viscosity which is altered by a loss of free water and which, in turn, influences blood flow needed for aerobic muscular work. This study examines changes in the rheologic properties of blood which attend changes in plasma volume with bed rest in humans and correlates these changes with alterations in aerobic capacity. Eight healthy human subjects were studied on the 6th day of bed rest during two consecutive 10-d bed rest periods separated by a 14-d recovery interval designed to simulate the flight-layover schedule of shuttle astronauts. Plasma viscosity was measured with a Wells-Brookfield viscometer, plasma volume by dye dilution, and maximal aerobic capacity (VO2max) by recumbent cycle ergometry. Bed rest resulted in significant increases in hematocrit and in total plasma protein concentration and fibrinogen concentration, both of which contribute to an elevation in plasma viscosity. The greater than 20% increase in fibrinogen concentration was much greater than could be explained by hemoconcentration. VO2max decreased significantly in the first but not the second bed rest cycle. In many individuals, a decrease in plasma volume and aerobic capacity was coupled with elevated plasma viscosity and hematocrit; however, significant correlations between these variables were lacking. Although significant rheologic perturbations do occur with bed rest, in this study, blood viscosity elevation failed to directly correlate with the reduction in VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of simulated weightlessness and gamma-irradiation on myocardial cells and osteoblasts.

The effects of simulated weightlessness and gamma-irradiation on the structure and function of the myocardial cells and osteoblasts were investigated with a rotating clinostat and 2 Gy 60Co gamma-irradiation. The results showed: (1) Under the simulated weightlessness (SWL), the diameter of the myocardial cells decreased 40%. And the long-short diameter proportion decreased 70%, (P < 0.01); SWL affected the cell skeleton and the distribution of microfilament became ununiform, the orientation was unclear; SWL had significant effects on osteoblast disintegration and proliferation. The disintegration function decreased and the proliferation process was inhibited; (2) 2 Gy 60Co gamma-ray irradiation had significant effects on Lactate Dehydrogenase (LDH) activity and Superoxide Dismutase (SOD), Malonaldehyde (MDA) content in the myocardial cells, (P < 0.05) (5) A synergistic effect was observed between irradiation and SWL.

Animals↗

[Changes of early components of auditory ERPs during HDT-simulated weightlessness].

Objective. To study changes of early components of the auditory ERPs during simulated weightlessness. Method. The event-related potentials (ERPs) during an auditory location discrimination were compared between head down tilt (HDT) and head up tilt (HUT) conditions in 14 normal subjects. Result. The early components of T-ERPs and NT-ERPs decreased significantly during HDT as compared with that during HUT. The reduction of mean potential amplitude during HDT was more marked at left-forehead area (F5). Conclusion. These data provided further evidence showing that the early activity process of brain was also affected by simulated weightlessness.

Adult↗