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NASA NTRS1994

Effects of Increased CO2 Level on the Well-Being, Growth and Renal Function of Rats

On the Space Shuttle the mean CO2 levels have been 0.3% which is ten times normal air, while there have been extended periods with mean levels of 0.7% and peak concentrations of 2%. On the Space Station the projected mean concentration of CO2 is 0.7% and not to exceed 1.0%. To ensure that high level of CO2 does not compromise the integrity of the science on the Space Station, the effects of chronic exposure to high levels of CO2 were investigated. Following 7 days of cage adaptation animals exposed to 2% CO2 for 30 days were compared to control (ambient air) animals and the effects on the well-being, growth and renal function analyzed. Ten male rats per group were placed in individual metabolic cages which allowed monitoring of daily food and water consumption, as well as feces and urine to be collected. Cages were placed in a plexiglass chamber with internal environment controlled by a computer in conjunction with gas sensors. The elevated CO2 was held constant at 2.0 +/- 0.03% and the O2 at 20.9 +/- 0.15%. Body weight and food and water intake were measured daily for the first ten days of exposure and then every three to four days for the remaining three weeks. Urine was measured for pH, CO2 (as an indicator for bicarbonate) and ammonia (as an indicator for ammonium). During 2% CO2 exposure, animal growth, weight, food and water consumption were within normal ranges suggesting that their well-being was not affected. Urine pH decreased from 7.12 to 6.77 over the first 6 days of exposure and increased the following 24 days returning to pre-exposure levels. Urine NH4+ increased 68% the first 6 days then dropped to and remained at 29% higher than pre-exposure level. Urine bicarbonate concentration did not change the first 6 days, but significantly increased by day 30. These results of chronic exposure to 2% C02 are consistent with renal compensation for respiratory acidosis which may impact science conducted on the Space Shuttle or the Space Station if CO2 levels reach 2%.

Lang, C.↗
NASA NTRS1994

Effects of Growth Hormone/IGF-I and Exercise on Unloaded Bones

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) in combination with exercise prevent muscle atrophy induced by unloading in the tail-suspension rat model for space flight (Gosselink et al, FASEB J 1994). This study evaluated the effects of these treatments on bone. Hypophysectomized rats were suspended (S) and treated with 1mg/kg/day CH plus IGF-I (H) or vehicle (Sal) daily by injection and exercised (Ex) by 3 climbs up a 1m ladder carrying a load equal to 30% the initial body weight (BW) 3x/day for 10 days. Tibial epiphysis (Epi) widths were measured by micrometry and femoral Bone Mineral Content (fBMC) in excised femurs by DEXA (Lunar DPX-L). Serum calcium (Ca) and phosphorus (Pi) were measured by COBAS Autoanalyzer (Roche Diag.). Ambulatory (Amb)-H treated rats showed growth rates of 6.6+-0.9 g/day, similar to S-H-Ex and higher than S-H (3.210.6, p less than 0.05) and S-Sal (-0.711.0, p less than 0.05). Epi widths were 10% lower in S-Sal, and S-Sal-Ex, and increased 100% in all H groups. fBMC was less in S than Amb, only when all S groups are compared to both Amb groups (p less than 0.03). H treatment increased fBMC (p less than 0.05) but reduced fBMC/100g BW in all H groups (p less than 0.001). The reduced density of H bone cannot be attributed to low circulating Ca. and Pi since they were higher in H than Sal (p less than 0.001). H treatment for 10 days in doses sufficient to support normal growth in BW failed to produce normal Epi widths or fBMC, even when combined with exercise. The suspension effect observed in Epi widths was not corrected by H or Ex alone, but was improved by H plus a This regimen. although effective in preventing muscle atrophy, failed to return bone measures, Epi widths and fBMC, to normal.

Harper, J. S.↗
NASA NTRS1995

Effects of Chronic 2.0% and 0.7% CO2 Exposures on the Well-Being, Growth and Renal Function of Rats

On the Space Shuttle and MIR, mean CO2 levels have been 0.3% which is ten times that of normal air. There have also been extended periods with levels of 0.7% CO2 with peak concentrations at 2.0%. The Space Station program had proposed that CO2 concentration levels be maintained, on average, at 0.7%, and not to exceed 1.0%. To ensure that these levels of CO2 would not compromise the integrity of the science performed on the Space Station, the effects of chronic exposure of rats to 2.0% and 0.7% CO2 were investigated. Ten male rats per group were placed in individual metabolic cages for monitoring of food and water consumption, as well as fecal and urine production. Cages were placed in a large (4W x 10L x 4H ft.) plexiglass chamber with a controlled atmospheric environment. Following 7 days of cage adaptation, animals were exposed to experimental (2.0% or 0.7% CO2) or control (ambient air) conditions for 30 days. Daily body weight, food and water intake, and fecal and urine excretions were measured for the last three days of adaptation and the first ten days of exposure and then every three to four days for the remaining three weeks. Urine was measured for pH and total CO2. During 2.0% and 0.7% CO2 exposures, animal growth, fecal production and food and water consumption were within normal ranges. Urine excretion was significantly (p less than 0.05) higher in both experimental groups compared to controls. Urine pH of animals exposed to 2.0% CO2 was decreased by 0.32 over the first 6 days of exposure, followed by a 0.63 increase by day 30. In animals exposed to 0.7% CO2, urine pH did not decrease early in the exposure period, but did increase by 0.37 by day 30. Urine CO2 excretion did not change the first 6 days of exposure, but significantly increased in both 2.0% and 0.7% CO2 by day 30 (897 and 402 mmol/day, respectively). These results of chronic exposure to 2.0% and 0.7% CO2 are consistent with renal compensation in response to an altered acid-base homeostasis. These findings may impact science conducted on the Space Shuttle or the Space Station if CO2 concentrations reach 0.7%.

Lang, C. K.↗
NASA NTRS1995

Pros and Cons of Using Water Immersion to Simulate Physiological Responses to Microgravity

Head-out water immersion (HOI) has been employed as a remedial treatment for various ills and ailments for many millennia, and total body immersion even longer as protective encapsulation for the mammalian fetus. Two discrete differences between stimuli induced by true microgravity (10(exp -4) g) and HOI are readily apparent. External water pressure on the skin and accompanying negative pressure breathing cause blood to shift headward. Secondly, the gravitational force is ever present during immersion and microgravity, but its effect is essentially neutralized during Earth orbital flight. Thus, the physiological responses to immersion should not be expected to match those during microgravity. Immersion has been used mainly to study and understand kidney function and associated cardiovascular responses for control of body fluid volume and osmotic content, with some application to and simulation of microgravity responses. There is a plethora of data from human HOI studies, but relatively few controlled data from microgravity studies. In general, it appears that physiological responses occur more quickly with water immersion than in microgravity, but this may be due to less rigorous control (voluntary and involuntary) of the preflight state of crew members. The central venous pressure-vasopressin (Gauer-Henry) reflex control for fluid balance may not be of prime importance in microgravity. Gross functions such as reduced body weight and water, level of hypovolemia, decreased isokinetic strength, and lower nitrogen balance found during immersion are qualitatively similar in microgravity, but the mechanisms controlling these and other functions are, for the most part, unclear. Only acquisition of data from well-controlled microgravity experiments will resolve this discrepancy.

Greenleaf, J. E.↗
NASA NTRS1996

Differences in Mechanical Properties of the Human and Monkey Tibia

A method which uses an instrument that detects the response of a long bone to a vibratory stimulus to quantify mechanical properties non-invasively was revised and validated for use in the tibia. Stored data from healthy men was reanalyzed and compared with values from non-human primates. The analysis uses the relationship K(sub b) = 48 EI/L(sup 3) where K(sub b) is the lateral stiffness of a beam with force applied midspan, E is the elastic modulus, I the geometric moment of inertia and L, the limb length. Values for stiffness (EI, Nm(sup2)), the Euler buckling load (P(sub cr) = EI (pi/L)(sup 2)), and bone sufficiency (S) which represents the axial load the bone can support, adjusted to BW (S=P(sub cr)/BW) were obtained. The interest precision of the method in relaxed men, 5.8%, and in sedated male monkeys, 4.3%, was based on repeated measures in the same subjects at 1 month intervals. The R tibias of 40 men, aged 38.6 +/- 7.3 yrs with BW 78.9 +/- 7.9 kg, showed average (+/- SD) L to be 35 +/- 2 cm, EI 222 +/- 71 Nm(sup 2), P(sub cr) 18.1 +/- 4.9 kN, and S 23.4 +/- 5.7 N. The R tibias of 24 Rhesus monkeys ranging in age from 2-12 years, BW 4.9 +/- 3 kg, showed L to be 14.7 +/- 1.9 cm, EI 6.0 +/- 4.8 Nm(sup 2), P(sub cr) 2.51 +/- 1.2 kN and S 57.3 N. These measurements indicate that the tibia of a terrestrial non-human primate, M. mulatta, has higher load carrying capacity for the level of body weights in the species than the human bone.

Arnaud, Sara B.↗
NASA NTRS1996

Daily Supine LBNP Treadmill Exercise Maintains Upright Exercise Capacity During 14 Days of Bed Rest

Exposure to microgravity or bed rest reduces upright exercise capacity. Exercise modes, durations, and intensities which will effectively and efficiently counteract such deconditioning are presently unresolved. We that daily supine treadmill interval training with lower body negative pressure (LBNP) would prevent reduction in upright exercise capacity during 14 days of 6 deg. head-down bed rest (BR). Eight healthy male subjects underwent two 14 day BR protocols separated by 3 months. In a crossover design, subjects either remained at strict BR or performed 40 min of daily exercise consisting of supine walking and running at intensities varying from 40-80% of pre-BR upright peak oxygen uptake (VO2). LBNP during supine exercise was used to provide 1.0 to 1.2 times body weight of footward force. An incremental upright treadmill test to measure submaximal and peak exercise responses was given pre- and post-BR. In the non-exercise condition, peak VO2 and time to exhaustion were reduced 16 +/- 4% and 10 +/- 1% (p less than 0.05), respectively, from pre-BR. With LBNP exercise these variables were not significantly different (NS) from pre-BR. During submaximal treadmill speeds after BR, heart rate was higher (11 +/- 11 bpm, p less than 0.05) and respiratory exchange ratio was elevated (p less than 0.05) in the no exercise condition. Both were maintained at pre-BR levels in the LBNP exercise condition (NS from pre-BR). Since this supine treadmill interval training with addition of LBNP maintained upright exercise responses and capacity during BR, this countermeasure may also be effective during space flight.

Ertl, Andy C.↗
NASA NTRS1996

Renal Response to Chronic Centrifugation in Rats

Previously reported effects of chronic centrifugation on renal function in mammals are contradictory. The present study was conducted as an effort to provide a comprehensive analysis of renal response to chronic centrifugation (12 days at +2 Gz). Sixteen male Sprague-Dawley rats (210-230 g) were used: eight centrifuged (EC) and eight off centrifuge controls (OCC). During centrifugation EC had lower body weight and food consumption. EC showed a decrease (72%) in water intake for the first two days (T1 and T2) followed by significant increases from T4-T6. EC urine output increased two-fold over the first four days, returning to baseline by T9. EC urea excretion was elevated on T3 through T5. Creatinine, Na(+), K(+), and osmolar excretion were lower than OCC over the last four days of the study. Assuming constant plasma osmolarity and creatinine levels, EC free water clearance (C(sub H2O)) was elevated significantly on T4 when the peak urine output was exhibited. EC also had a greater C(sub H2O) over the last four days, associated with a significantly lower osmolar clearance and GFR. The initial diuresis exhibited during centrifugation can be attributed to a reduced water resorption and increased urea excretion. This diuresis was mediated independent of changes in GFR over the first eight days. However, differences in excretion seen after eight days of centrifugation are probably GFR mediated which would imply animals established a new homeostatic setpoint by that time. Centrifugation elicites an acute alteration in fluid homeostasis followed by adaptation within a week.

Ortiz, Rudy M.↗
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 NTRS1998

Comparison of Upright Gait with Supine Bungee-Cord Gait

Running on a treadmill with bungee-cord resistance is currently used on the Russian space station MIR as a countermeasure for the loss of bone and muscular strength which occurs during spaceflight. However, it is unknown whether ground reaction force (GRF) at the feet using bungee-cord resistance is similar to that which occurs during upright walking and running on Earth. We hypothesized-that the DRAMs generated during upright walking and running are greater than the DRAMs generated during supine bungee-cord gait. Eleven healthy subjects walked (4.8 +/- 0.13 km/h, mean +/- SE) and ran (9.1 +/- 0.51 km/h) during upright and supine bungee-cord exercise on an active treadmill. Subjects exercised for 3 min in each condition using a resistance of 1 body weight calibrated during an initial, stationary standing position. Data were sampled at a frequency of 500Hz and the mean of 3 trials was analyzed for each condition. A repeated measures analysis of variance tested significance between the conditions. Peak DRAMs during upright walking were significantly greater (1084.9 +/- 111.4 N) than during supine bungee-cord walking (770.3 +/- 59.8 N; p less than 0.05). Peak GRFs were also significantly greater for upright running (1548.3 +/- 135.4 N) than for supine bungee-cord running (1099.5 +/- 158.46 N). Analysis of GRF curves indicated that forces decreased throughout the stance phase for bungee-cord gait but not during upright gait. These results indicate that bungee-cord exercise may not create sufficient loads at the feet to counteract the loss of bone and muscular strength that occurs during long-duration exposure to microgravity.

Boda, Wanda L.↗
NASA NTRS2002

Rodent Biocompatibility Test Using the NASA Foodbar and Epoxy EP21LV

Epoxy has been used successfully to affix NASA foodbars to the inner walls of the Animal Enclosure Module for past space flight experiments utilizing rodents. The epoxy used on past missions was discontinued, making it necessary to identify a new epoxy for use on the STS-108 and STS-107 missions. This experiment was designed to test the basic biocompatibility of epoxy EP21LV with male rats (Sprague Dawley) and mice (Swiss Webster) when applied to NASA foodbars. For each species, the test was conducted with a control group fed untreated foodbars and an experimental group fed foodbars applied with EP21LV. For each species, there were no group differences in animal health and no statistical differences (P<0.05) in body weights throughout the study. In mice, there was a 16% increase in heart weight in the epoxy group; this result was not found in rats. For both species, there were no statistical differences found in other organ weights measured. In rats, blood glucose levels were 15% higher and both total protein and globulin were 10% lower in the epoxy group. Statistical differences in these parameters were not found in mice. For both species, no statistical differences were found in other blood parameters tested. Food consumption was not different in rats but water consumption was significantly decreased 10 to 15% in the epoxy group. The difference in water consumption is likely due to an increased water content of the epoxy-treated foodbars. Finally, both species avoided consumption of the epoxy material. Based on the global analysis of the results, the few parameters found to be statistically different do not appear to be a physiologically relevant effect of the epoxy material, We conclude that the EP21LV epoxy is biocompatible with rodents.

Tillman, J.↗
NASA NTRS2002

Effects of Hypergravity Rearing on Growth Hormone (GH) Secretion In Preweanling Rats

We previously reported that rat pups reared at 1.5-g, 1.75 or 2.0-g hypergravity weigh 6-15% less than 1.0-g controls. To account for these findings. we measured the lactational hormones, prolaction (Prl) and oxytocin (OT), in the pups' mothers. Gravity related differences in Prl were not observed whereas OT of lactating dams was significantly reduced relative to controls. Milk transfer from dam to pup was not impaired in hypergravity-reared litters tested at 1-g. Together, these findings suggest that impaired lactation and milk transfer do not account for reduced body masses of postnatal rats reared in hypergravity. In the present study, we analyzed growth hormone (GH) secretion and maternal licking in pups reared in hypergravity and in 1.0-g controls. Recent reports using dwarfing phenotypes in mouse mutants have provided evidence for postnatal dependence on GH and insulin-like growth factors (IGFs). Beginning on Gestational day (G)11 of the rats' 22 day pregnancy, rat dams and their litters were exposed to either 1.5-g, 1.75-g or 2.0-g. On Postnatal day (P)10, we measured plasma GH using enzyme immunoassay (EIA). Contrary to our hypothesis, GH was significantly elevated in pups reared at 2.0-g relative to 1.0-g controls. Pup-oriented behaviors of the hypergravity dams were also changed, possibly accounting for the increase in pup GH. GH alone does not appear to play a role in reduced body weights of hypergravity-reared pups.

Baer, L. A.↗
NASA NTRS1991

Spinoff From a Moon Suit

Al Gross transferred expertise obtained as an ILC engineer for NASA's Apollo program to the manufacture of athletic shoes. Gross substituted DuPont's Hytrel plastic for foam materials in the shoe's midsole, eliminating cushioning loss caused by body weight. An external pressurized shell applied from space suit technology was incorporated into the shoe. Stiffness and cushioning properties of the midsole were "tuned" by varying material thickness and styling lines. A stress free "blow molding" process adapted from NASA space suit design was also utilized. The resulting compression chamber midsole performed well in tests. It allows AVIA to re-configure for specific sports and is a "first step" toward a durable, foamless, non-fatiguing midsole.

Source record↗
NASA NTRS2003

Use of a Slick-Plate as a Contingency Exercise Surface for the Treadmill With Vibration Isolation System

The treadmill with vibration isolation system (TVIS) was developed to counteract cardiovascular, musculoskeletal, and neurovestibular deconditioning during long-duration missions to the International Space Station (ISS). However, recent hardware failures have necessitated the development of a short-term, temporary contingency exercise countermeasure for TVIS until nominal operations could be restored. The purpose of our evaluation was twofold: 1) to examine whether a slick-plate/contingency exercise surface (CES) could be used as a walking/running surface and could elicit a heart rate (HR) greater than or equal to 70% HR maximum and 2) to determine the optimal hardware configuration, in microgravity, to simulate running/walking in a 1-g environment. One subject (male) participated in the slick surface evaluation and two subjects (one male, one female) participated in the microgravity evaluation of the slick surface configuration. During the slick surface evaluation, the subject was suspended in a parachute harness and bungee cord configuration to offset the subject's body weight. Using another bungee cord configuration, we added a vertical load back to the subject, who was then asked to run for 20 minutes on the slick surface. The microgravity evaluation simulated the ISS TVIS, and we evaluated two different slick surfaces (Teflon surface and an aluminum surface coated with Tufram) for use as a CES. We evaluated each surface with the subject walking and running, with and without a handrail, and while wearing either socks or nylon booties over shoes. In the slick surface evaluation, the subject ran for 20 minutes and reached a maximum HR of 170 bpm. In the microgravity evaluation, the subjects chose the aluminum plate coated with Tufram as the CES, while wearing a pair of nylon booties over running shoes and using a handrail, as the optimal hardware configuration. The results indicate that the CES may provide an interim capability to counteract aerobic deconditioning until TVIS can be returned to an operational status. No indices of musculoskeletal or neurovestibular deconditioning were evaluated. Future studies are needed to validate the efficacy of CES in countering aerobic deconditioning and the effects, if any, on musculoskeletal and neurovestibular deconditioning.

James A. Loehr↗
NASA NTRS2004

Ethnic Differences in Bending Stiffness of the Ulna and Tibia

There is considerable information about the variations in bone mass associated with different opportunity to compare a mechanical property of bone in young college women of Caucasian, Hispanic and Asian descent who gave informed consent to participate in an exercise study. The subjects were sedentary, in good health, eumenorrheic, non-smokers and had body mass indices (BMI) less than 30. Measurements acquired were body weight, kg, and height, cm, calcaneal and wrist bone density, g/square cm (PIXI, Lunar GE) and bending stiffness (EI, Nm(exp 2)) in the ulna and tibia. E1 was determined non-invasively with an instrument called the Mechanical Response Tissue Analyzer (MRTA) that delivers a vibratory stimulus to the center of the ulna or tibia and analyzes the response curve based on the equation E1 = k(sub b) L(exp 3)/48 where k, is lateral bending stiffness, L is the length of the bone, E is Young's modulus of elasticity and I, the bending moment of inertia. The error of the test (CV) based on measurements of an aluminum rod with a known E1 was 4.8%, of calcaneal BMD, 0.54%, and of wrist bone density, 3.45%.

Arnaud, S. B.↗
NASA NTRS2003

Lumbar spine disc heights and curvature: upright posture vs. supine compression harness

INTRODUCTION: Spinal lengthening in microgravity is thought to cause back pain in astronauts. A spinal compression harness can compress the spine to eliminate lengthening but the loading condition with harness is different than physiologic conditions. Our purpose was to compare the effect of spine compression with a harness in supine position on disk height and spinal curvature in the lumbar spine to that of upright position as measured using a vertically open magnetic resonance imaging system. METHODS: Fifteen healthy subjects volunteered. On day 1, each subject lay supine for an hour and a baseline scan of the lumbar spine was performed. After applying a load of fifty percent of body weight with the harness for thirty minutes, the lumbar spine was scanned again. On day 2, after a baseline scan, a follow up scan was performed after kneeling for thirty minutes within the gap between two vertically oriented magnetic coils. Anterior and posterior disk heights, posterior disk bulging, and spinal curvature were measured from the baseline and follow up scans. RESULTS: Anterior disk heights increased and posterior disk heights decreased compared with baseline scans both after spinal compression with harness and upright posture. The spinal curvature increased by both loading conditions of the spine. DISCUSSION: The spinal compression with specially designed harness has the same effect as the physiologic loading of the spine in the kneeling upright position. The harness shows some promise as a tool to increase the diagnostic capabilities of a conventional MR system.

Non-NASA Center↗
NASA NTRS2000

Dependence of normal development of skeletal muscle in neonatal rats on load bearing

Antigravity function plays an important role in determining the morphological and physiological properties of the neuromuscular system. Inhibition of the normal development of the neuromuscular system is induced by hindlimb unloading during the neonatal period in rats. However, the role of gravitational loading on the development of skeletal muscle in rats is not well understood. It could be hypothesized that during the early postnatal period, i.e. when minimal weight-supporting activity occurs, the activity imposed by gravity would be of little consequence in directing the normal development of the skeletal musculature. We have addressed this issue by limiting the amount of postnatal weight-support activity of the hindlimbs of rats during the lactation period. We have focused on the development of three characteristics of the muscle fibers, i.e. size, myonuclear number and myosin heavy chain expression.

Non-NASA Center↗
NASA NTRS2002

Leptin regulates bone formation via the sympathetic nervous system

We previously showed that leptin inhibits bone formation by an undefined mechanism. Here, we show that hypothalamic leptin-dependent antiosteogenic and anorexigenic networks differ, and that the peripheral mediators of leptin antiosteogenic function appear to be neuronal. Neuropeptides mediating leptin anorexigenic function do not affect bone formation. Leptin deficiency results in low sympathetic tone, and genetic or pharmacological ablation of adrenergic signaling leads to a leptin-resistant high bone mass. beta-adrenergic receptors on osteoblasts regulate their proliferation, and a beta-adrenergic agonist decreases bone mass in leptin-deficient and wild-type mice while a beta-adrenergic antagonist increases bone mass in wild-type and ovariectomized mice. None of these manipulations affects body weight. This study demonstrates a leptin-dependent neuronal regulation of bone formation with potential therapeutic implications for osteoporosis.

NASA Discipline Regulatory Physiology↗
NASA NTRS2003

Effects of hindlimb unweighting on the mechanical and structure properties of the rat abdominal aorta

Previous studies have shown that hindlimb unweighting of rats, a model of microgravity, reduces evoked contractile tension of peripheral conduit arteries. It has been hypothesized that this diminished contractile tension is the result of alterations in the mechanical properties of these arteries (e.g., active and passive mechanics). Therefore, the purpose of this study was to determine whether the reduced contractile force of the abdominal aorta from 2-wk hindlimb-unweighted (HU) rats results from a mechanical function deficit resulting from structural vascular alterations or material property changes. Aortas were isolated from control (C) and HU rats, and vasoconstrictor responses to norepinephrine (10(-9)-10(-4) M) and AVP (10(-9)-10(-5) M) were tested in vitro. In a second series of tests, the active and passive Cauchy stress-stretch relations were determined by incrementally increasing the uniaxial displacement of the aortic rings. Maximal Cauchy stress in response to norepinephrine and AVP were less in aortic rings from HU rats. The active Cauchy stress-stretch response indicated that, although maximum stress was lower in aortas from HU rats (C, 8.1 +/- 0.2 kPa; HU, 7.0 +/- 0.4 kPa), it was achieved at a similar hoop stretch. There were also no differences in the passive Cauchy stress-stretch response or the gross vascular morphology (e.g., medial cross-sectional area: C, 0.30 +/- 0.02 mm(2); HU, 0.32 +/- 0.01 mm(2)) between groups and no differences in resting or basal vascular tone at the displacement that elicits peak developed tension between groups (resting tension: C, 1.71 +/- 0.06 g; HU, 1.78 +/- 0.14 g). These results indicate that HU does not alter the functional mechanical properties of conduit arteries. However, the significantly lower active Cauchy stress of aortas from HU rats demonstrates a true contractile deficit in these arteries.

Non-NASA Center↗