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PubMed1997

Changes in radioactive tracer distribution in rats after 24 hours of 45 degrees hind limb unweighting.

INTRODUCTION: Changes in radioactive tracer distribution were examined in rats after exposure to a simulated microgravity model of 45 degrees head down tilt (45HDT) or 45 degrees hind limb unweighting (45HU) for up to 24 h. METHODS: Rats were randomly assigned to either 45HDT (or 45HU) experimental groups or control groups for each time point of 0.5 h, 1 h, 2 h, 4 h, 8 h, or 24 h. The 0.5-h through 8-h experimental rats were anesthetized and placed head-down on a ramp at 45 degrees, while control rats were placed in a prone position. Non-anesthetized rats in the 24-h experimental group were tail-suspended at 45 degrees, while control rats were allowed unrestrained movement. Technetium-labeled diethylenetriamine pentaacetate (99mTcDTPA, physical half-life of 6.02 h, MW = 492 amu) and indium-labeled diethylenetriamine pentaacetate (111In DTPA, physical half-life of 3.5 d, MW = 545 amu) were used to measure body organ distributions of the radioactive tracers at the 0.5-h-8-h and 24-h time points, respectively. Major organs were harvested after each time period and measured for radioactive counts. Light and electron micrographs were examined. RESULTS: Mean 111InDTPA counts for the lungs, kidneys, and brains of the 24 h 45HU groups were significantly higher than control counts. Light and electron microscopy demonstrated the development of pulmonary edema in the alveolar septal areas after 2 h of 45HDT, and a shift in edema to the pulmonary airways and pulmonary arteries after 24 h of 45HU. CONCLUSIONS: Pulmonary edema development, accompanied by a significant increase in 111InDTPA lung, kidney, and brain counts in the 24-h 45HU groups, suggests vascular injury in the microcirculation of these organs.

Animals↗
PubMed2005

Readaptation from simulated microgravity as a stimulus for improved orthostatic tolerance: role of the renal, cardioendocrine, and cardiovascular systems.

BACKGROUND: Microgravity and simulated microgravity (SM) lead to important changes in orthostatic tolerance (OT), the autonomic nervous system (ANS), and the volume-regulating systems. After one is exposed to microgravity or SM, a period of readaptation to gravity is known to take place, but it is not certain if orthostatic function returns to baseline within the initial recovery and what mechanisms are involved. We hypothesized that after a period of recovery, OT, ANS, and volume-regulating systems would return to pre-SM levels. METHODS: To test this hypothesis, 24 healthy men were placed on a constant diet for 3 to 5 days, after which a tilt-stand test (pre-TST) was performed. The TST was repeated after 14 to 16 days of head-down tilt bed rest (HDTB) (post-TST) and a 3-day period of recovery (rec-TST), at which times measurements of renal, cardioendocrine, and cardiovascular systems were conducted. RESULTS: Presyncope occurred in 46% of subjects pre-TST, in 72% post-TST, and in 23% during rec-TST. OT was significantly better during the recovery period than at baseline (p = .03). There was a significant decrease in urinary sodium and potassium excretion, along with a decrease in plasma renin activity and serum and urine aldosterone compared with baseline. Serum norepinephrine and sympathetic responsiveness remained below baseline values. CONCLUSION: In summary, OT improved compared with baseline after a period of readaptation. Retention of electrolytes (sodium, potassium) could be involved. These findings indicate that recovery after SM is not simply a gradual return to baseline values but is instead a dynamic process reflecting interaction of multiple regulatory systems.

Adaptation, Physiological↗
PubMed2002

Yohimbine administration prevents over-responsiveness to epinephrine induced by simulated microgravity.

BACKGROUND: Simulated microgravity produces sustained inhibition of sympathoneural release, turnover, and synthesis of norepinephrine (NE) and hypersensitization of beta-adrenergic pathways. These changes may explain the orthostatic intolerance experienced by astronauts returning from spaceflights. HYPOTHESIS: Chronic administration of yohimbine would prevent the increase of beta-adrenergic hypersensitivity to epinephrine (Epi) induced by simulated microgravity. METHODS: Eight healthy young subjects received 8 mg of yohimbine (an antagonist of alpha2adrenoceptors) orally twice a day during the simulated microgravity achieved through -6 degrees head-down bed rest (HDBR). The catecholamine-induced lipolysis was studied on isolated fat cells from subcutaneous adipose tissue before HDBR and on the fifth day of HDBR. Epi was infused at three graded rates (0.01, 0.02, and 0.03 microg x kg(-1) x min(-1) for 40 min each) before and at the end of the HDBR period. The effects of Epi on the sympathetic nervous system (SNS) activity-assessed by plasma NE levels and spectral analysis of systolic BP and heart rate variability-and on plasma levels of glycerol, non-esterified fatty acids, glucose, and insulin and on energy expenditure were evaluated. RESULTS: Under yohimbine treatment, HDBR failed to modify urinary NE excretion and spectral variability of systolic BP in the mid-frequency range. The beta- and alpha-adrenergic sensitivity of fat cells were not modified by HDBR nor were plasma NE levels and spectral variability of systolic BP induced by Epi infusion. No alteration of Epi-induced changes in heart rate and systolic and diastolic BPs were observed after HDBR. Epi-induced increases in plasma glucose, insulin, glycerol, and non-esterified fatty acid levels as well as energy expenditure were also unmodified by HDBR. Only the Epi-induced plasma lactate level was increased by HDBR. CONCLUSION: Our data suggest that the increase in the effects of Epi induced during microgravity could be attenuated by chronic administration of yohimbine. An explanation for this effect could be SNS activation brought about by the alpha2-adrenoceptor antagonist properties of yohimbine.

Absorptiometry, Photon↗
PubMed2003

Renal and hormonal responses to isotonic saline infusion after 3 days' head-down tilt vs. supine and seated positions.

AIM: The study aimed to determine whether prolonged exposure to simulated microgravity produces a level of thoracic volume receptor loading similar to that seen in the upright position or immediately after lying down. METHODS: We used a cross-over design to compare responses to a saline infusion in eight healthy subjects during a 4-day, -6 degree head-down tilt (HDT) and in the acute seated and acute supine positions. RESULTS: The first 24 h of HDT were associated with greater urinary excretion of water and sodium (UV, UNaV) than seated and acute supine [cumulative UV, 3035 +/- 219, 2311 +/- 156 (P < 0.05), and 2448 +/- 182 mL (P < 0.05), respectively; cumulative UNaV, 256 +/- 19, 180 +/- 11 (P < 0.05), and 189 +/- 15 mmol (P < 0.05), respectively]. Haemoglobin and haematocrit were increased after 24 h and plasma volume decreased after 48 h of HDT (P < 0.05). With prolongation of HDT, UV and UNaV returned near the baseline values, and plasma atrial natriuretic factor (ANF) and renin values returned to acute seated levels; in acute supine, ANF values were higher and renin lower than in the two other positions. After a 30-min infusion of 20 mL kg(-1) isotonic saline on the fourth HDT day or during acute seated or acute supine, sodium excretion within 4 h was similar during HDT and acute seated (83 +/- 6 and 84 +/- 9 mmol, respectively) and greater during supine (104 +/- 8 mmol, P < 0.05). The renin decrease was greater in HDT and seated than in supine. The plasma ANF increase was greater during HDT than during supine; during seated, plasma ANF was unchanged. CONCLUSION: These data suggest that, after 4 days of HDT, thoracic volume receptor loading returns to the same level as in the seated position, leading to blunted responses to volume expansion as compared with the acute supine position.

Adult↗
PubMed1996

Modulation of myocardial alpha 1- but not beta-adrenoceptors after 90-day tail-suspension.

We have previously demonstrated that prolonged simulated microgravity (tail-suspension) leads to cardiac alterations with increased resting heart rate, myocardial degradation changes and attenuated myocardial contractility. The present study investigated the potential role of adrenoceptor mechanisms underlying them. Changes of myocardial alpha 1-adrenoceptor (alpha 1-AR) and beta 1-adrenoceptor (beta-AR) in 90-day tail-suspended rats was investigated by the method of radioligand binding assay and application of Scatchard's method. The results showed significantly decreased quantity of specific binding of 125I-BE[2-beta-(4-hydroxy-3-[125I]indophenyl)-ethylaminomethyltetralone] to alpha 1-AR present in membrane derived from ventricular myocardium of the suspended animals, despite the affinity of the alpha 1-AR to 125I-Be was unchanged. But neither the quantity nor the affinity of beta-AR binding to 125I-Pindolol was significantly altered. In addition, the spontaneously beating rate of isolated right atria from tail-suspended animals showed little change in sensitivity and reactivity to the stimulations of graded phenylephrine (alpha-agonist, measured in the presence of beta-antagonist propranolol) and isoproterenol (beta-agonist), compared with the control rats. There were also no obvious differences of the effects of the isoproterenol on the contractility of isolated left ventricular papillary muscles between the two groups. Since myocardial alpha 1-AR mediated-effects include production of cardiac hypertrophy and enhancement of myocardial glucose uptake and glycolysis, the down-regulation of the alpha 1-AR may be a contributor to the cardiac cellular accumulation and the myocardial degradation changes as found in our tail-suspended rats. The data from this study also suggest that the myocardial beta-adrenoceptors are not affected by the prolonged tail-suspension.

Adrenergic alpha-Agonists↗
PubMed2006

Why is orthostatic tolerance lower in women than in men? Renal and cardiovascular responses to simulated microgravity and the role of midodrine.

BACKGROUND: Exposure to microgravity induces cardiovascular deconditioning, manifested by orthostatic intolerance (OI). We assessed the renal, cardioendocrine, and cardiovascular responses of women and men to simulated microgravity to examine the impact of gender on OI. METHODS: Fifteen healthy female and 14 healthy male subjects were given a constant diet for 3 to 5 days, after which they underwent a tilt-stand test (pre-TST) and began 14 to 16 days of head-down tilt bed rest (HDTB), followed by a repeat tilt-stand test (post-TST). Female subjects began HDTB so that the post-TST was at the same time in their menstrual cycle as their pre-TST. Twenty-four-hour urine collections (daily), hormonal measurements, plethysmography, and cardiovascular system identification were performed. RESULTS: The times to presyncope were significantly different for men and women before (p= .005) and after HDTB (p= .001), with all of the women but only 50% of the men experiencing presyncope during the pre-TST (p= .002) and all of the women but only 64% of the men experiencing presyncope during the post-TST. At baseline, the following differences between women and men were observed: women had higher serum aldosterone levels (p = .02), higher parasympathetic responsiveness (p = .01), lower sympathetic responsiveness (p = .05), and lower venous compliance (p = .05). Several parameters changed with HDTB in both men and women. In a double-blinded randomized trial, midodrine (5 mg orally) or placebo given to female subjects 1 hour before post-TST was ineffective in preventing 01. CONCLUSION: In conclusion, the frequency of OI is higher in women than in men and is not modified by midodrine at the dose used. This increased susceptibility is likely secondary to intrinsic basal differences in the activity of volume-mediated parasympathetic and adrenergic systems and in venous tone. Thus, approaches to reduce OI in women are likely to differ from those effective in men.

Adaptation, Physiological↗
PubMed2000

Exercise thermoregulation in men after 1 and 24-hours of 6 degrees head-down tilt.

BACKGROUND: Exercise thermoregulation is dependent on heat loss by increased skin blood flow (convective and conductive heat loss) and through enhanced sweating (evaporative heat loss). Reduction of plasma volume (PV), increased plasma osmolality, physical deconditioning, and duration of exposure to simulated and actual microgravity reduces the ability to thermoregulate during exercise. HYPOTHESIS: We hypothesized that 24 h of head down tilt (HDT24) would alter thermoregulatory responses to a submaximal exercise test and result in a higher exercise rectal temperature (Tre) when compared with exercise Tre after 1 h of head down tilt (HDT1). METHODS: Seven men (31+/-SD 6 yr, peak oxygen uptake (VpO2peak) of 44+/-6 ml x kg(-1) x min(-1)) were studied during 70 min of supine cycling at 58+/-SE 1.5% VO2peak at 22.0 degrees C Tdb and 47% rh. RESULTS: Relative to pre-tilt sitting chair rest data, HDT1 resulted in a 6.1+/-0.9% increase and HDT24 in a 4.3+/-2.3% decrease in PV (delta = 10.4% between experiments, p<0.05) while plasma osmolality remained unchanged (NS). Pre-exercise Tre was elevated after HDT24 (36.71 degrees C +/-0.06 HDT1 vs. 36.93 degrees C+/-0.11 HDT24, p<0.05). The 70 min of exercise did not alter this relationship (p<0.05) with respective end exercise increases in Tre to 38.01 degrees C and 38.26 degrees C (degrees = 1.30 degrees C (HDT1) and 1.33 degrees C (HDT24)). While there were no pre-exercise differences in mean skin temperature (Tsk), a significant (p<0.05) time x treatment interaction occurred during exercise: after min 30 in HDT24 the Tsk leveled off at 31.1 degrees C, while it continued to increase reaching 31.5 degrees C at min 70 in HDT1. A similar response (NS) occurred in skin blood velocity. Neither local sweating rates nor changes in body weight during exercise of -1.63+/-0.24 kg (HDT1) or - 1.33+/-0.09 kg (HDT24) were different (NS) between experiments. CONCLUSION: While HDT24 resulted in elevated pre-exercise Tre, reduced PV, attenuation of Tsk and skin blood velocity during exercise, the absolute increase in exercise Tre was not altered. But if sweat rate and cutaneous vascular responses were similar at different core temperatures (unchanged thermoregulation), the Tre offset could have been caused by the HDT-induced hypovolemia.

Adult↗
PubMed1999

Five myofibrillar lesion types in eccentrically challenged, unloaded rat adductor longus muscle--a test model.

Sarcomere disruptions are observed in the adductor longus (AL) muscles following voluntary reloading of spaceflown and hindlimb suspension unloaded (HSU) rat, which resemble lesions in eccentrically challenged muscle. We devised and tested an eccentric contraction (ECCON) test system for the 14-day HSU rat AL. Six to 7 hours following ECCON, ALs were fixed to allow immunostaining and electron microscopy (EM). Toluidine blue-stained histology semithin sections were screened for lesion density (#/mm2). Serial semithin sections from the ECCON group were characterized for myosin immunointensity of lesions. Five myofibrillar lesion types were identified in histological semithin sections: focal contractions; wide A-bands; opaque areas; missing A-bands; and hyperstretched sarcomeres. Lesion density by type was greater for ECCON than NonECCON ALs (P< or =0.05; focal contractions and opaque regions). Lesion density (#-of-all-five-types/mm2) was significantly different (ECCON: 23.91+/-10.58 vs. NonECCON: 5.48+/-1.28, P< or =0.05; ECCON vs. SHAM: 0.00+/-0.00; P< or = 0.025). PostECCON optimal tension decreased (Poi-drop, 17.84+/-4.22%) and was correlated to lesion density (R2=0.596), but prestretch tension demonstrated the highest correlation with lesion density (R2=0.994). In lesions, the darkly staining A-band lost the normally organized thick filament alignment to differing degrees across the different lesion types. Ranking the five lesion types by a measure of lesion length deformation (hypercontracted to hyperstretched) at the light microscopy level, related to the severity of thick filament registry loss across the lesion types at the electron microscopic level. This ranking suggested that the five lesion types seen in semithin sections at the light level represented a lesion progression sequence and paralleled myosin immunostaining loss as the distorted A-band filaments spread across the hyperlengthening lesion types. Lesion ultrastructure indicated damage involved calcium homeostasis loss (focal contraction lesions) and "thick-filament-centering" failure of titin (wide A-band lesions) in the early stages of lesion development.

Animals↗
PubMed2000

Artificial gravity as a countermeasure in long-duration space flight.

Long-duration exposure to weightlessness results in bone demineralization, muscle atrophy, cardiovascular deconditioning, altered sensory-motor control, and central nervous system reorganizations. Exercise countermeasures and body loading methods so far employed have failed to prevent these changes. A human mission to Mars might last 2 or 3 years and without effective countermeasures could result in dangerous levels of bone and muscle loss. Artificial gravity generated by rotation of an entire space vehicle or of an inner chamber could be used to prevent structural changes. Some of the physical characteristics of rotating environments are outlined along with their implications for human performance. Artificial gravity is the centripetal force generated in a rotating vehicle and is proportional to the product of the square of angular velocity and the radius of rotation. Thus, for a particular g-level, there is a tradeoff between velocity of rotation and radius. Increased radius is vastly more expensive to achieve than velocity, so it is important to know the highest rotation rates to which humans can adapt. Early studies suggested that 3 rpm might be the upper limit because movement control and orientation were disrupted at higher velocities and motion sickness and chronic fatigue were persistent problems. Recent studies, however, are showing that, if the terminal velocity is achieved over a series of gradual steps and many body movements are made at each dwell velocity, then full adaptation of head, arm, and leg movements is possible. Rotation rates as high as 7.5-10 rpm are likely feasible. An important feature of the new studies is that they provide compelling evidence that equilibrium point theories of movement control are inadequate. The central principles of equilibrium point theories lead to the equifinality prediction, which is violated by movements made in rotating reference frames.

Coriolis Force↗
PubMed1994

Orthostatic hypotension in patients, bed rest subjects, and astronauts.

Orthostatic hypotension after even short space flights has affected a significant number of astronauts. Given the need for astronauts to function at a high level of efficiency during and after their return from space, the application of pharmacologic and other treatments is strongly indicated. This report addresses the clinical problem of orthostatic hypotension and its treatments to ascertain whether pharmacologic or physiologic treatment may be useful in the prevention of orthostatic hypotension associated with space flight. Treatment of orthostatic hypotension in patients now includes increasing intravascular volume with high sodium intake and mineralocorticoids, or increasing vascular resistance through the use of drugs to stimulate alpha or block beta vascular receptors. Earlier treatment used oral sympathomimetic ephedrine hydrochloride alone or with "head-up" bed rest. Then long-acting adrenocortical steroid desoxycorticosterone preparations with high-salt diets were used to expand volume. Fludrocortisone was shown to prevent the orthostatic drop in blood pressure. The combination of the sympathomimetic amine hydroxyamphetamine and a monoamine oxidase inhibitor tranylcypromine has been used, as has indomethacin alone. Davies et al. used mineralocorticoids at low doses concomitantly with alpha-agonists to increase vasoconstrictor action. Schirger et al used tranylcypromine and methylphenidate with or without a Jobst elastic leotard garment or the alpha-adrenergic agonist midodrine (which stimulates both arterial and venous systems without direct central nervous system or cardiac effects). Vernikos et al established that the combination of fludrocortisone, dextroamphetamine, and atropine exhibited a beneficial effect on orthostatic hypotension induced by 7-day 6 degrees head-down bed rest (a model used to simulate the weightlessness of space flight). Thus, there are numerous drugs that, in combination with mechanical techniques, including lower body negative pressure to elevate transmural pressure, could be studied to treat orthostatic hypotension after space flight.

Animals↗
PubMed2004

Modeled microgravity disrupts collagen I/integrin signaling during osteoblastic differentiation of human mesenchymal stem cells.

Spaceflight leads to reduced bone mineral density in weight bearing bones that is primarily attributed to a reduction in bone formation. We have previously demonstrated severely reduced osteoblastogenesis of human mesenchymal stem cells (hMSC) following 7 days culture in modeled microgravity (MMG). One potential mechanism for reduced osteoblastic differentiation is disruption of type I collagen (Col I)-integrin interactions and reduced integrin signaling. Integrins are heterodimeric transmembrane receptors that bind extracellular matrix (ECM) proteins and produce signals essential for proper cellular function, survival, and differentiation. Therefore, we investigated the effects of MMG on integrin expression and function in hMSC. We demonstrate that 7 days of culture in MMG leads to reduced expression of the ECM protein, Col I. Conversely, MMG consistently increases Col I-specific alpha2 and beta1 integrin protein expression. Despite this increase in integrin subunit expression, autophosphorylation of adhesion-dependent kinases, focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2), is significantly reduced. Activation of Akt protein kinase (Akt) is unaffected by the reduction in FAK activation. However, reduced downstream signaling via the Ras-mitogen activated protein kinase (MAPK) pathway is evidenced by a reduction in Ras and extracellular signal-related protein kinase (ERK) activation. Taken together, our findings indicate that MMG decreases integrin/MAPK signaling, which likely contributes to the observed reduction in osteoblastogenesis.

Cell Differentiation↗
PubMed2005

Neuromuscular adaptations to spaceflight are specific to postural muscles.

The effects of microgravity were determined in muscles of differing function and myofiber-type composition. Rats were assigned either to a 10-day spaceflight mission or to ground-based control conditions. Following the experimental period, hindlimb muscles were obtained from both groups. Cytofluorescent techniques were used to examine neuromuscular junctions (NMJs) from both slow- and fast-twitch fibers. Histochemical procedures were employed to assess myofiber profiles (size and type). Results indicate that microgravity did not alter NMJ structure or myofiber profile in the tibialis anterior, a predominantly fast-twitch, nonpostural muscle. Similarly, the NMJs and myofibers of deep regions of the gastrocnemius, a locomotor muscle possessing a mixed fiber population, were unaffected by spaceflight. In contrast, both myofibers and NMJs of the soleus-a postural muscle-demonstrated significant (P < 0.05) plasticity following exposure to spaceflight. Moreover, NMJs of both fast- and slow-twitch myofibers displayed similar remodeling in that muscle. Our findings suggest that the deleterious effects of microgravity are most apparent among postural muscles, and are manifested both in myofibers and their synapses.

Adaptation, Physiological↗
PubMed1995

Changes in stiffness induced by hindlimb suspension in rat soleus muscle.

Soleus muscle atrophy was induced by hind-limb suspension of rats for 3 weeks with the intention of inducing a relative increase in the percentage of fast-twitch fibres and assessing modifications in muscle stiffness. A method of dual controlled releases was used to obtain tension/extension curves and force/velocity relationships characterizing the mechanical behaviour of the soleus. Fibre typing was achieved by myofibrillar adenosine 5'-triphosphatase staining. Results showed that hindlimb suspension decreased the percentage of slow-twitch fibres (-31%) to the profit of fast-twitch fibres (+370%) and intermediate fibres (+255%). This led to an increase in maximal shortening velocity. Tension/extension curves indicated a decrease in soleus stiffness after 3 weeks of unloading. Changes in elastic properties are interpreted in terms of modifications occurring in the active part and the passive part of the so-called series elastic component. These changes also suggest that the parameters derived from a twitch are inappropriate to account for modifications in speed-related properties of muscle.

Adaptation, Physiological↗
PubMed1996

Mechanical and electrical changes in human muscle after dry immersion.

The effects of a 7-day dry immersion, with the body protected from contact with the water, were investigated in six subjects. Changes in contraction properties were studied in the triceps surae muscle. After immersion, the maximal voluntary contraction (MVC) was reduced by 33.8% (P < 0.01), and the electrically evoked maximal tetanic contraction (Po) was reduced by 8.2% (P > 0.05). The difference between Po and MVC expressed as a percentage of Po and referred to as force deficiency was also calculated. The force deficiency increased by a mean of 44.1% (P < 0.01) after immersion. The decrease in Po was associated with increased maximal rates of tension development (7.2%) and of tension relaxation. The twitch time to peak was not significantly changed, and half relaxation and total contraction time were decreased by 5.3% and 2.8%, respectively, but the twitch tension (Pt) was not significantly changed and the Pt:Po ratio was decreased by 8.7% after immersion. The muscle surface action potential showed an increase in duration (18.8%) and decreases in amplitude and total area (14.6% and 2.8%; P < 0.05-0.01, respectively). Comparison of the electrical and mechanical alterations recorded during the voluntary contractions, and in the contractions evoked by electrical stimulation of the motor nerve, would suggest that immersion not only modified the peripheral processes associated with contraction, but also changed the central and/or neural command of the contraction. At peripheral sites, it is proposed that the intracellular processes of contraction played a role in the contractile impairment recorded during immersion.

Action Potentials↗
PubMed1994

Effects of growth hormone on rat skeletal muscle after hindlimb suspension.

To examine the effects of growth hormone (GH) on the preferential atrophy of the soleus muscle (SOL) occurring after hindlimb suspension (HS), two groups of male rats received daily injections of 2 IU.kg-1 body mass of recombinant human growth hormone (rhGH). Rats were either suspended by the tail for 21 days (HS-GH, n = 5) or nonsuspended (C-GH, n = 5). The effects of rhGH treatment on SOL and extensor digitorum longus muscles (EDL) were compared in two groups of animals receiving daily injections of saline, either suspended by the tail (HS-SA, n = 5) or nonsuspended (C-SA, n = 5). The results showed that the SOL hypertrophy in response to rhGH administration was mostly observed in C rats (+33%, P < 0.01). This increase in muscle mass was correlated with a concomitant increase in the size of type I fibres (+21%, P < 0.05). Although SOL mass decreased during HS in rhGH treated animals (-44%, P < 0.001), the mean normalized mass of this muscle did not significantly differ between C-SA and HS-GH groups. A statistically significant increase in the absolute mass of EDL occurred with rhGH treatment in C-GH (+12%, P < 0.05). The HS-induced decrease in the percentage distribution of type I fibres in SOL was unaffected by the rhGH treatment. In addition, a decrease in the citrate synthase activity in the whole SOL was observed in the two groups of tail-suspended rats (-31%, P < 0.05; -21%, P < 0.05 in SA and GH animals, respectively).2+ f1p4

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1986

Plasma vasopressin, neurophysin, renin and aldosterone during a 4-day head-down bed rest with and without exercise.

The purpose of this study was to investigate the main renal and hormonal responses to head-down bed rest, which is currently considered a reliable experimental model for the simulation of weightlessness. Urinary output and electrolytes, plasma renin activity (PRA), aldosterone (PA), antidiuretic hormone (ADH) and immunoreactive neurophysin-I (Np) were measured in eight adult volunteers submitted to a 4-day head-down bed rest (-6 degrees) after a 24-h control period in the horizontal position (day 0). Four of the eight subjects were submitted to two 1-h periods of controlled muscular exercise (50% VO2max) from day 1 to day 4. Throughout the head-down bed rest period, urinary output remained stable, although lower than in the control period (day 0), but the urinary Na/K ratio decreased. Plasma electrolytes and osmolality, and creatinine clearance remained unchanged. There was no significant difference between exercising and non-exercising subjects. At the hormonal level, PRA and PA increased during the head-down bed rest. This increase was more pronounced in the group with exercise. At the end of the tilt period, PRA and PA were about 3 times higher than on day 1. No significant changes could be observed for ADH and Np. It is concluded that a 4-day head-down bed rest results in no apparent changes in neurohypophyseal secretory activity, and in a progressive secondary hyperaldosteronism.

Adult↗
PubMed1986

The effect of hypokinesia and hypodynamia on protein turnover and the growth of four skeletal muscles of the rat.

An animal suspension model has been used to simulate the weightlessness experienced during space travel. This procedure results in a reduction in the normal shortening (i.e. hypokinesia) and force generation functions of hind limb muscles (i.e. hypodynamia). The ensuing muscle atrophy was studied over 12 days in different muscle types. Slow muscles (e.g. the soleus) underwent a more pronounced atrophy than intermediate (i.e. gastrocnemius) and fast phasic muscles (e.g. extensor digitorum longus). In all muscle types inactivity resulted in a smaller accumulation of DNA and losses of RNA and protein after 5 days. The latter arose from a decrease in the rate of protein synthesis (measured in vivo) and an increase in protein breakdown. Increased specific activities of cathepsins B and D also supported the view that there is an increased proteolysis after hypokinesia and hypodynamia. When the inactive soleus was simultaneously held in a lengthened (stretched) state the atrophy was prevented through a large increase in the fractional rate of protein synthesis. Protein degradation remained elevated with stretch, thereby slowing the growth of these muscles relative to those in pair-fed, ambulatory controls. The much smaller atrophy of the tibialis anterior and extensor digitorum longus muscles in suspended only limbs represented an underestimate of the true atrophic effects of hypokinesia and hypodynamia. In this model gravity pulls the suspended foot into a plantar flexed position, thereby permanently stretching and protecting such flexor muscles. When this influence of stretch was removed a greater atrophy ensued, mainly due to the loss of the stretch-induced stimulation of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗