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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
NASA NTRS1994

Human parathyroid hormone-(1-38) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats

The purpose of this study was to determine if human parathyroid hormone-(1-38) (PTH) can restore cancellous bone mass to the established osteopenic, immobilized proximal tibial metaphyses (PTM) of female rats. The right hindlimbs of six-month-old female Sprague-Dawley rats were immobilized by bandaging the right hindlimbs to the abdomen. After 30 days of right hindlimb immobilization (RHLI), the rats were subcutaneously injected with 200 microgram hPTH(1-38)/kg/day for 15 (short-term) or 75 (longer-term) days. Static bone histomorphometry was performed on the primary spongiosa, while both static and dynamic histomorphometry were performed on the secondary spongiosa of the right PTM. Immobilization for 30 days without treatment decreased trabecular bone area, number and thickness in both primary and secondary spongiosa, and induced an increase in eroded perimeter and a decrease in tissue referent-bone formation rate (BFR/TV) in the secondary spongios. These changes reached a new steady state thereafter. Treatment with 200 microgram hPTH(1-38)/kg/day for 15 days, beginning at 30 days post immobilization (IM), significantly increased trabecular bone area, thickness and number in both primary and secondary spongiosa despite continuous IM when compared to the age-related and IM controls. The short-term (15 days) PTH treatment significantly increased labeling perimeter, mineral apposition rate and BFR/TV in the secondary spongiosa and stimulated longitudinal bone growth as compared to the age-related and IM controls. PTH treatment for longer-term (75 days) further increased trabecular bone area, thickness and number as compared to aging and IM controls and short-term (15 days) PTH treated groups. The bone formation indices in the secondary spongiosa of these longer-term treated rats were lower than that of short-term (15 days) PTH treated group, but they were still higher than those of IM and age-related controls. Our findings indicate that PTH treatment stimulates cancellous bone formation, restores and adds extra cancellous bone to the established, disuse-osteopenic proximal tibial metaphysis of continuously RHLI female rats. These results suggest that PTH may be a useful agent in treatment disuse-induced osteoporosis in humans.

Ma, Y. F.↗
NASA NTRS1995

Stimulation of Myofibrillar Protein Synthesis in Hindlimb Suspended Rats by Resistance Exercise and Growth Hormone

The objective of this study was to determine the ability of a single bout of resistance exercise alone or in combination with recombinant human growth hormone (rhGH) to stimulate myofibrillar protein synthesis (Ks) in hindlimb suspended (HLS) adult female rats. Plantar flexor muscles were stimulated with resistance exercise, consisting of 10 repetitions of ladder climbing on a 1 m grid (85 deg.), carrying an additional 50% of their body weight attached to their tails. Saline or rhGH (1 mg/kg) was administered 30' prior to exercise, and Ks was determined with a constant infusion of H-3-Leucine at 15', 60', 180', and 360' following exercise. Three days of HLS depressed Ks is approx. equal to 65% and 30-40% in the soleus and gastrocnemius muscles, respectively (p is less than or equal to 0.05). Exercise increased soleus Ks in saline-treated rats 149% 60' following exercise (p less than or equal to 0.05), decaying to that of non-exercised animals during the next 5 hours. Relative to suspended, non-exercised rats rhGH + exercise increased soleus Ks 84%, 108%, and 72% at 15', 60' and 360' following exercise (p is less than or equal to 0.05). Gastrocnemius Ks was not significantly increased by exercise or the combination of rhGH and exercise up to 360' post-exercise. Results from this study indicate that resistance exercise stimulated Ks 60' post-exercise in the soleus of HLS rats, with no apparent effect of rhGH to enhance or prolong exercise-induced stimulation. Results suggests that exercise frequency may be important to maintenance of the slow-twitch soleus during non-weightbearing, but that the ability of resistance exercise to maintain myofibrillar protein content in the gastrocnemius of hindlimb suspended rats cannot be explained by acute stimulation of synthesis.

Linderman, Jon K.↗
NASA NTRS1992

Effects of Daily Administration of Prostaglandin E2 and Its Withdrawal on the Lumbar Vertebral Bodies in Male Rats

The effects of daily prostaglandin E2 (PGE2) treatment (on) and PGE2 treatment followed by withdrawal (on-off) on cancellous bone in lumbar vertebral bodies were studied in 7 month-old male Sprague-Dawley rats. The first groups of rats were given daily subcutaneous injections of 0, 1, 3, and 6 mg PGE2/kg/d for 60,120, and 180 days, and the second group of rats were given PGE2 for 60 days followed by withdrawal for 60 and 120 days. Histomorphometric analyses were performed on double-fluorescent labeled undecalcified sections of fourth lumbar vertebral bodies. Systemic PGE2 treatment elevated cancerous bone mass of lumbar vertebral bodies 26-60%, above control levels within 60 days and continued treatment maintained it for another 120 days, but the excess bone was lost after the treatment was witndrawn. PGE2 treatment for 60 days increased trabecular bone area, trabecular width, and bone formation parameters, and shortened remodeling periods in a dose-response manner. These changes were sustained at the levels achieved by 60-day treatment in the rats treated for 120 and 180 days. The eroded perimeter increased at day 60 and further at day 120 and then plateaued. In the on-off treated rats, the cancenous bone area, bone formation, and resorption parameters returned to near age-related controls by 60 days after withdrawal and were maintained there after 120 days of withdrawal. Therefore, we conclude that the continuous treatment is needed in order to maintain the PGE2-induced bone gain. When these findings were compared to those previously reported for the proximal tibial metaphyses, we found that the proximal tibial spongiosa was much more responsive to PGE2 treatment than the fourth lumbar vertebral body.

Ke, Hua Zhu↗
NASA NTRS1993

Prostaglandin E2 Restores Cancellous Bone to Immobilized Limb and Adds Bone to Overloaded Limb in Right Hindlimb Immobilization Rats

The purpose of this study was to determine whether prostaglandin E2 (PGE2) can restore cancellous bone mass and architecture to osteopenic, continuously immobilized (IM), proximal tibial metaphysis (PTM) in female rats. The right hindlimb of three and one-half-month-old Sprague-Dawley female rats were immobilized by right hindlimb immobilization (RHLI) in which the right hindlimb was underloaded and the contralateral left limb was overloaded during ambulation. After 4 or 12 weeks of RHLI, the rats were treated with 3 or 6 mg PGE2/kg/day and RHLI for 8 or 16 weeks. Bone histomorphometry was performed on microradiographs of PTM. Immobilization (IM) induced a transient cancellous bone loss and decreased trabecular thickness, number and node density, and increased free end density that established a new steady state after 4 weeks of IM. Three or 6 mg PGE2/kg/d for 8 weeks beginning at 4 or 12 weeks of IM completely restored cancellous bone mass (+127 to +188 percent) and structure to the age-related control levels in spite of continuous IM. Another 8 weeks of treatment maintained bone mass and architecture at these levels. No differences in cancellous bone mass and architecture were found between the overloaded PTM or RHLI rats and the age-related controls. However, 3 and 6 mg/kg/d of PGE2 treatment started at 4 or 12 weeks for 8 weeks significantly increased cancellous bone mass in the overloaded PTM (+45 to +74% of untreated controls), and another 8 weeks of treatment maintained bone mass at these levels. Our findings indicate that daily 3 or 6 mg PGE2/kg/d treatment restores and maintains PTM cancellous bone mass in continuously immobilized (right) tibiae, and adds and maintains extra bone to slightly overloaded PTM cancellous bone in female rats.

Li, M.↗
NASA NTRS1996

Cardiopulmonary Changes with Moderate Decompression in Rats

Sprague-Dawley rats were compressed to 616 kPa for 120 min then decompressed at 38 kPa/min to assess the cardiovascular and pulmonary responses to moderate decompression stress. In one series of experiments the rats were chronically instrumented with Doppler ultrasonic probes for simultaneous measurement of blood pressure, cardiac output, heart rate, left and right ventricular wall thickening fraction, and venous bubble detection. Data were collected at base-line, throughout the compression/decompression protocol, and for 120 min post decompression. In a second series of experiments the pulmonary responses to the decompression protocol were evaluated in non-instrumented rats. Analyses included blood gases, pleural and bronchoalveolar lavage (BAL) protein and hemoglobin concentration, pulmonary edema, BAL and lung tissue phospholipids, lung compliance, and cell counts. Venous bubbles were directly observed in 90% of the rats where immediate post-decompression autopsy was performed and in 37% using implanted Doppler monitors. Cardiac output, stroke volume, and right ventricular wall thickening fractions were significantly decreased post decompression, whereas systemic vascular resistance was increased suggesting a decrease in venous return. BAL Hb and total protein levels were increased 0 and 60 min post decompression, pleural and plasma levels were unchanged. BAL white blood cells and neutrophil percentages were increased 0 and 60 min post decompression and pulmonary edema was detected. Venous bubbles produced with moderate decompression profiles give detectable cardiovascular and pulmonary responses in the rat.

Robinson, R.↗
NASA NTRS1999

Effects of Spaceflight on Bone: The Rat as an Animal Model for Human Bone Loss

The loss of weight bearing during spaceflight results in osteopenia in humans. Decrements in bone mineral reach 3-10% after as little as 75-184 days in space. Loss of bone mineral during flight decreases bone strength and increases fracture risk. The mechanisms responsible for, and the factors contributing to, the changes in bone induced by spaceflight are poorly understood. The rat has been widely used as an animal model for human bone loss during spaceflight. Despite its potential usefulness, the results of bone studies performed in the rat in space have been inconsistent. In some flights bone formation is decreased and cancellous bone volume reduced, while in others no significant changes in bone occur. In June of 1996 Drs. T. Wronski, S. Miller and myself participated in a flight experiment (STS 78) to examine the effects of glucocorticoids on bone during weightlessness. Technically the 17 day flight experiment was flawless. The results, however, were surprising. Cancellous bone volume and osteoblast surface in the proximal tibial metaphysis were the same in flight and ground-based control rats. Normal levels of cancellous bone mass and bone formation were also detected in the lumbar vertebrae and femoral neck of flight rats. Furthermore, periosteal bone formation rate was found to be identical in flight and ground-based control rats. Spaceflight had little or no effect on bone metabolism! These results prompted us to carefully review the changes in bone observed in, and the flight conditions of previous spaceflight missions.

Halloran, B.↗
NASA NTRS1997

Rat Gestation During Space Flight: Outcomes for Dams and Their Offspring Born After Return to Earth

Sprague-Dawley rats were studied to learn whether gestation in the near-zero gravity, high radiation environment of space impacts selected mammalian postnatal events. Ten rats spent days nine to twenty of pregnancy aboard the space shuttle orbiter Atlantis (STS-66). Their movement was studied shortly after return to Earth; subsequently, several of their offspring were cross-fostered and examined through postnatal day 81 (P81) for whole body growth and somatic motor development. Values for the flight animals were compared to ground-based control groups. Relative to controls, the pregnant flight rats showed a marked paucity of locomotion during the first few hours after returning to Earth. There was greater likelihood of perinatal morbidity for the offspring of flight dams when compared to the control groups. Whole body weight of surviving offspring, averaged for each group separately, showed typical sigmoidal growth curves when plotted against postnatal age. The flight group for our study had a larger ratio of female to male pups, and that was sufficient to account for the lower average daily weight gained by the flight animals when compared to the control groups. Walking was universally achieved by P13 and preceded eye opening, which was complete in all pups by P17. Thus, both of these developmental horizons were attained on schedule in the flight as well as the control rats. Characteristic changes were observed in hind limb step length and gait width as the pups grew. These patterns occurred at the same time in each group of rats. Therefore, prenatal space flight from days nine to twenty of gestation did not interfere with the establishment of normal patterns for hind paw placement during walking.

Wong, Andre M.↗
NASA NTRS2000

Resting Energy Expenditure of Rats Acclimated to Hyper-Gravity

To determine the influence of body mass and age on resting energy expenditure (EE) following acclimation to hyper-gravity, oxygen consumption (VO2) and carbon dioxide production (VCO2) were measured to calculate resting energy expenditure (EE), in male rats, ages 40 to 400 days, acclimated to 1.23 or 4.1 G for a minimum of two weeks. Animals were maintained on a centrifuge to produce the hyper-gravity environment. Measurements were made over three hours in hyper-gravity during the period when the lights were on, the inactive period of rats. In rats matched for body mass (approximately 400 g) hyper-gravity increased VO2 by 18% and VCO2 by 27% compared to controls, resulting in an increase in RER, 0.80 to 0.87. There were increases in resting EE with an increase in gravity. This increase was greater when the mass of the rat was larger. Rating EE for 400g animals were increased from 47 +/- 1 kcal/kg/day at 1 G, to 57 +/- 1.5 and 5.8 +/- 2.2 kcal/kg/day at 2,3 and 4.1 G, respectively. There was no difference between the two hyper-gravity environments. When differences in age of the animals were accounted for, the increase in resting EE adjusted for body mass was increased by over 36% in older animals due to exposure to hyper-gravity. Acclimation to hyper-gravity increases the resting EE of rats, dependent upon body mass and age, and appears to alter substrate metabolism. Increasing the level of hyper-gravity, from 2.3 to 4.1 G, produced no further changes raising questions as to a dose effect of gravity level on resting metabolism.

Wade, Charles E.↗
NASA NTRS1997

Deoxypyridinoline in the Urine of Rats with Unloaded Hindlimbs

The urinary excretion of deoxypyridinoline (U-Dpd), a nonreducible collagen crosslink in bone released by osteoclastic activity, is thought to be an accurate marker of bone resorption. The role of increased resorption in the osteopenia of a space flight model which unloads the hindlimbs by suspending the tail is controversial. To assess skeletal resorption in the model we measured U-Dpd (Pyrilinks-D, Metro Biosystems, Inc.) in serial 24 hour urine specimens collected from 250 a (Y) and 450 a (M) male rats with unloaded hindlimbs for four weeks. Both groups of rats were fed AIN76 diets with calcium restricted to 0.2% in Y and to 0.1 % in M. Blood was obtained after 28 days for parathyroid hormone (PTH), 1,25-dihydroxyvitamin D (1,25-D) and alkaline phosphatase (Alkptase). Basal U-Dpd was higher and more variable in Y than M (475+/-200 vs 67+/-9, nM/mM creatinine, p<.001). Repeated measures ANOVA in Y revealed decreases in U-Dpd, 36% in control (C) and 24% in unloaded (S) rats (p<.005). There was a nadir in YS on the 14th day not observed in YC (p<.05). U-Dpd in MC showed no change, but increased in MS by the 14th day and remained elevated. At the end of the experiment, body weights in both Y and M were less in S than C (337+/-16 vs 306+/-12g and 485+/-10 vs 461+/-6g, p=.002). Bill was inversely related to U-Dpd only in M (r=0.699, p=.024). PTH, similar in C and S in Y (52+/-15 vs 42+/-7pg/ml, NS) and M (68+/-13 vs 61+/-12, NS), was unrelated to U-Dpd. 1,25-D tended toward higher values in YC than YS (197+/-103 vs 119+/-30, NS) and correlated with U-Dpd (0.773, p=.015). Alkptase, 1.3 times higher in Y than M, was similar in C and S at the end of unloading. These findings indicate that bone resorption, as reflected by U-Dpd, is suppressed in young and stimulated in mature rats exposed to a space flight model. U-Dpd reflects reduced growth from the diet change in young control and experimental rats and loss of Bill in mature animals exposed to the space flight model, 2 situations with opposite effects on bone resorption.

Arnaud, Sara B.↗
NASA NTRS2001

A Novel Telometric Metric for In-Situ Measurement of Intrauterine Pressure (IUP) in Pregnant and Parturient Rats

During labor and birth, considerable forces exerted on fetuses help instigate certain adaptive postpartum responses (viz., breathing and suckling). To make precise, reliable measures of the forces experienced by rat fetuses during parturition, we developed a novel method for measuring intrauterine pressure (IUP) in late pregnant rats. A small (1.25 x 4cm) telemetric blood pressure sensor is fitted within a fluid-filled balloon, similar in size to a full term rat fetus. The balloon is surgically implanted in the uterus on Gestational Day 19 of the rats' 22-day pregnancy. During birth, dams are able to deliver their pups and the balloon. IUP arsenals are recorded during labor (G22 or 23) and birth. Data derived from a group of implanted rats indicated that pressures on the balloon increased across the period of birth, reaching 18 mmHg during labor, 25 mmHg during pup births and 39 mmHg just prior to delivery of the balloon. These data are within the range reported for conventional IUP measurement techniques. Dams are simultaneously videotaped, enabling us to analyze behavioral expressions of labor contractions and to integrate in-situ and behavioral findings.

Baer, Lisa A.↗
NASA NTRS1999

Absence of Change in Total Daily Energy Expenditure (EE(sub TD)) in Young and Mature Rats During 14 Days of Hypergravity

Effect of age on the response of EE(sub TD) to an increase in gravity was assessed in young (Y; 1.5 month old) and mature (M; 8 month old) Sprague-Dawley rats. Rats were implanted with transmitters to monitor activity, and metabolism was determined by the double labeled water technique. Daily food intake was measured. For each age, rats (n=8 per treatment) were exposed to centrifugation at 2G, or remained at 1G. There was a difference in EE(sub TD) between age groups, 182 plus or minus 11 and 143 plus or minus 5 kcal/kg/day in Y and M, respectively. This difference was attributed in part to a lower activity level in M animals, 48% of Y rats. After day 6 there was no effect on EE(sub TD) of exposure to 2G, or on food intake per 100g BW. Prior studies show a 20% increase in resting EE with hypergravity. In our study the level of activity was reduced to 41% of 1G in both age groups during 2G. For Y at 1G resting EE accounted for 78% of the EE(sub TD) and activity 22%, while at 2G resting EE was 96% of EE(sub TD) and activity 4%. M rats had similar changes. Independent of age, with exposure to hypergravity EE(sub TD) is maintained by behavioral changes.

Wade, C. E.↗
NASA NTRS2003

Intrauterine Pressure (IUP) Telemetry in Pregnant and Parturient Rats: Potential Applications for Spacecraft and Centrifugation Studies

Rats exposed to spaceflight or centrifugation from mid-to late pregnancy undergo either more or fewer labor contractions at birth, respectively, as compared to those in normal Earth gravity (1-g). In this paper, we report the development and validation of a new telemetric method for quantifying intrauterine pressure (IUP) in freely-moving, late pregnant and parturient rats. We plan to utilize this technique for studies of labor in altered gravity, specifically, to ascertain forces of uterine during birth, which we believe may be changed in micro- and hypergravity. The technique we describe yields precise, reliable measures of the forces experienced by rat fetuses during parturition. A small, surgically-implantable telemetric pressure sensor was fitted within a fluid-filled balloon. The total volume of the sensor-balloon assembly matched that of a full term rat fetus. Real-time videorecordings of sensor-implanted rat dams and non- implanted control dams enabled us to characterize effects of the intrauterine implant on behavioral aspects of parturition. Contraction frequency, duration, pup-to-pup birth intervals and pup-oriented activities of the dams measured during the peri-birth period were unaffected by the sensor implant. These findings establish intrauterine telemetry as a reliable, non-invasive technique for quantifying intrauterine pressures associated with parturition on Earth and in altered gravity environments. This new technology, readily amenable to spaceflight and centrifugation platforms, will enable us to answer key questions regarding the role of altered labor frequency labor in the adaptation of newborn mammals to hypo- and hypergravity.

Ronca, A. E.↗
NASA NTRS2002

Alteration of gene expression profiles in skeletal muscle of rats exposed to microgravity during a spaceflight

To clarify the mechanism of skeletal muscle wasting during spaceflights, we investigated whether intramuscular gene expression profiles are affected, by using DNA microarray methods. Male rats sent on the 17-day NASA STS-90 Neurolab spaceflight were sacrificed 24 hours after return to earth (MG group). Ground control rats were maintained for 17 days in flight-simulated cages (CS group). Spaceflight induced a 19% and 23% loss of tibialis anterior and gastrocnemius muscle mass, respectively, as compared to ground controls. Muscle RNA was analyzed by the Clontech Atlas DNA expression array in four rats, with two MG/ CS pairs for the tibialis anterior, and one pair for the gastrocnemius. Alterations in gene expression were verified for selected genes by reverse-transcription PCR. In both muscles of MG rats, mRNAs for 12 genes were up-regulated by over 2-fold, and 38 were down-regulated compared to controls. There was inhibition of genes for cell proliferation and growth factor cascades, including cell cycle genes and signal transduction proteins, such as p21 Cip1, retinoblastoma (Rb), cyclins G1/S, -E and -D3, MAP kinase 3, MAD3, and ras related protein RAB2. These data indicate that following exposure to microgravity, there is downregulation of genes involved in regulation of muscle satellite cell replication.

NASA Program Fundamental Space Biology↗
NASA NTRS2001

The Spacelab 3 simulation: basis for a model of growth plate response in microgravity in the rat

Data from Spacelab 3 (SL3) suggested that spaceflight significantly reduces the activity of the rat tibial growth plate. Animal processing after SL3 began twelve hours post-landing, so data reflect post-flight re-adaptation in addition to spaceflight effects. To determine if a twelve-hour period of weight bearing after seven days of unloading could affect the physes of spaceflown rats, the present study assessed the growth plate response to unloading with or without a reloading period. Rats were subjected to hind-limb suspension for seven days and then euthanized, with or without twelve hours of reloading. Activity of the growth plate was assessed by morphometric analysis. Rats suspended without reloading had reserve zone (RZ) height greater than controls, and shorter hypertrophy/calcification zone (HCZ) with fewer cells. The greater RZ was associated with a larger cell area, indicating a possible mitotic delay or secretion defect. Twelve hours of reloading decreased RZ height and cell number, and restored the number of cells in HCZ to control values, but the number of cells in the proliferative zone and height in HCZ were reduced. These results suggest the rebound response to preserve/restore skeletal function after a period of unloading involves an acceleration of growth associated with a decreased cell cycle time in PZ. Changes during the reloading period in this simulation support our hypothesis that the effects of spaceflight on SL3 growth plates were altered by changes that occurred post-landing. The similarities in response to unloading by suspension or during spaceflight are used to propose a model of growth plate response during spaceflight.

manned↗
NASA NTRS2002

Resting energy expenditure of rats acclimated to hypergravity

BACKGROUND: The use of centrifugation at 1 G has been advocated as a control condition during spaceflight and as a countermeasure to compensate for the adverse effects of spaceflight. Rodents are the primary animal model for the study of the effects of spaceflight and will be used in the evaluation of centrifugation as a countermeasure and means of control at 1 G during flight. HYPOTHESIS: The present study was designed to assess whether resting energy expenditure (EER) of male rats was increased in relation to the magnitude of the level of gravity to which the animals were exposed. The influence of body mass and age on resting energy expenditure (EER) of male rats (n = 42, age 40-400 d) was determined following 2 wk of acclimation to 1, 2.3, or 4.1 G. Hypergravity environments were created by centrifugation. Measurements were made at the gravity level to which the animal was acclimated and during the lights-on period. RESULTS: In rats matched for body mass (approximately 400 g), mean O2 consumption and CO2 production were higher (18% and 27%, respectively) in the 2.3- and 4.1 -G groups than controls. Mean respiratory exchange ratio (RER) increased from 0.80 to 0.87. EER was increased from 47 +/- 0.1 kcal x d(-1) at 1 G, to 57 +/- 1.5 and 58 +/- 2.2 kcal x d(-1) at 2.3 and 4.1 G, respectively. There was no difference in EER between the hypergravity groups. When age differences were considered, EER (kcal x kg(-1) x d(-1)) with increased gravity was 40% higher than at 1 G. The increase in EER was not proportional over gravity levels. CONCLUSION: Acclimation of rats to hypergravity increases their EER, dependent on body mass and age, and may alter substrate metabolism. The increase in EER was not related to the level of gravity increase.

NASA Center ARC↗
NASA NTRS2002

Increased GABA(A) inhibition of the RVLM after hindlimb unloading in rats

Attenuated baroreflex-mediated increases in renal sympathetic nerve activity (RSNA) in hindlimb unloaded (HU) rats apparently are due to changes within the central nervous system. We hypothesized that GABA(A) receptor-mediated inhibition of the rostral ventrolateral medulla (RVLM) is increased after hindlimb unloading. Responses to bilateral microinjection of the GABA(A) antagonist (-)-bicuculline methiodide (BIC) into the RVLM were examined before and during caudal ventrolateral medulla (CVLM) inhibition in Inactin-anesthetized control and HU rats. Increases in mean arterial pressure (MAP), heart rate (HR), and RSNA in response to BIC in the RVLM were significantly enhanced in HU rats. Responses to bilateral CVLM blockade were not different. When remaining GABA(A) inhibition in the RVLM was blocked by BIC during CVLM inhibition, the additional increases in MAP and RSNA were significantly greater in HU rats. These data indicate that GABA(A) receptor-mediated inhibition of RVLM neurons is augmented after hindlimb unloading. Effects of input from the CVLM were unaltered. Thus, after cardiovascular deconditioning in rodents, the attenuated increase in sympathetic nerve activity in response to hypotension is associated with greater GABA(A) receptor-mediated inhibition of RVLM neurons originating at least in part from sources other than the CVLM.

Non-NASA Center↗
NASA NTRS2002

Site- and compartment-specific changes in bone with hindlimb unloading in mature adult rats

The purpose of this study was to examine site- and compartment-specific changes in bone induced by hindlimb unloading (HU) in the mature adult male rat (6 months old). Tibiae, femora, and humeri were removed after 14, 21, and 28 days of HU for determination of bone mineral density (BMD) and geometry by peripheral quantitative computed tomography (pQCT), mechanical properties, and bone formation rate (BFR), and compared with baseline (0 day) and aging (28 day) controls. HU resulted in 20%-21% declines in cancellous BMD at the proximal tibia and femoral neck after 28 day HU vs. 0 day controls (CON). Cortical shell BMD at these sites was greater (by 4%-6%) in both 28 day HU and 28 day CON vs. 0 day CON animals, and nearly identical to that gain seen in the weight-bearing humerus. Mechanical properties at the proximal tibia exhibited a nonsignificant decline after HU vs. those of 0 day CON rats. At the femoral neck, a 10% decrement was noted in ultimate load in 28 day HU rats vs. 28 day CON animals. Middiaphyseal tibial bone increased slightly in density and area during HU; no differences in structural and material properties between 28 day HU and 28 day CON rats were noted. BFR at the tibial midshaft was significantly lower (by 90%) after 21 day HU vs. 0 day CON; this decline was maintained throughout 28 day HU. These results suggest there are compartment-specific differences in the mature adult skeletal response to hindlimb unloading, and that the major impact over 28 days of unloading is on cancellous bone sites. Given the sharp decline in BFR for midshaft cortical bone, it appears likely that deficits in BMD, area, or mechanical properties would develop with longer duration unloading.

Non-NASA Center↗
NASA NTRS2002

Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting

The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (approximately 300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 microM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N(omega)-nitro-L-arginine (L-NNA; 300 microM) reduced flow-induced dilation by 65-70% in Con and HLU 1As. In contrast, L-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with L-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of L-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10(-9)-10(-4) M) in soleus 2As. L-NNA reduced ACh-induced dilation by approximately 40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment with L-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.

Non-NASA Center↗