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Changes in potassium contractures due to simulated weightlessness in rat soleus muscle.

Some contractile properties of soleus muscle (SOL) fibers isolated from tail-suspended (21 days) rats were compared with those determined in the slow-twitch SOL and the fast-twitch extensor digitorum longus muscle (EDL) of control rats. In SOL from suspended rats, the resting membrane potential and the intracellular Na+ activity were typical of fast-twitch muscles. The relationship between the amplitude of K+ contractures and the membrane potential was steeper for control SOL than for control EDL and suspended SOL. The inactivation curve was also shifted to more positive potentials after suspension. In the presence of perchlorate anions, the tension activation curves of control EDL and suspended SOL were similarly shifted to more negative potentials. Thus, in the present study, modifications induced by suspension in SOL, mainly related to changes in the voltage-sensing process involved in the excitation-contraction coupling mechanism, were that the SOL assumed some of the characteristics of fast-twitch muscles.

Animals↗

Reversal of weightlessness-induced musculoskeletal losses with androgens: quantification by MRI.

Microgravity causes rapid decrement in musculoskeletal mass is associated with a marked decrease in circulatory testosterone levels, as we reported in hindlimb-suspended (HLS) rats. In this model which simulates microgravity, we hypothesized that testosterone supplementation should prevent these losses, and we tested this in two studies. Muscle volumes and bone masses were quantitated by using magnetic resonance imaging (MRI) on day 12. In the first study, 12-wk-old Sprague-Dawley rats that were HLS for 12 days lost 28.5% of muscle volume (53.3 +/- 4.8 vs. 74.5 +/- 3.6 cm3 in the ground control rats; P < 0.001) and had a 5% decrease in bone mineral density (BMD) (P < 0.05). In the second study, 30 male 12-wk-old Wistar rats were HLS and were administered either a vehicle (control), testosterone, or nandrolone decanoate (ND). An additional 20 rats were used as ground controls, one-half of which received testosterone. HLS rats had a significant reduction in muscle volume (42.9 +/- 3.0 vs. 56 +/- 1.8 cm3 in ground control rats; P < 0.01). Both testosterone and ND treatments prevented this muscle loss (51.5 +/- 2 and 51.6 +/- 1.2 cm3, respectively; a 63% improvement; P < 0. 05). There were no statistical differences between the two active treatment groups nor with the ground controls. Similarly, there was an 85% improvement in BMD in the testosterone group (1.15 +/- 0.04 vs. 1.04 +/- 0.04 density units in vehicle controls; P < 0.05) and a 76% improvement in the ND group (1.13 +/- 0.07 density units), whereas ground control rats had a BMD of 1.17 +/- 0.03 density units. Because serum testosterone levels are markedly reduced in this model of simulated microgravity, androgen replacement seems to be a rational countermeasure to prevent microgravity-induced musculoskeletal losses.

Anabolic Agents↗

Amino acid supplementation alters bone metabolism during simulated weightlessness.

High-protein and acidogenic diets induce hypercalciuria. Foods or supplements with excess sulfur-containing amino acids increase endogenous sulfuric acid production and therefore have the potential to increase calcium excretion and alter bone metabolism. In this study, effects of an amino acid/carbohydrate supplement on bone resorption were examined during bed rest. Thirteen subjects were divided at random into two groups: a control group (Con, n = 6) and an amino acid-supplemented group (AA, n = 7) who consumed an extra 49.5 g essential amino acids and 90 g carbohydrate per day for 28 days. Urine was collected for n-telopeptide (NTX), deoxypyridinoline (DPD), calcium, and pH determinations. Bone mineral content was determined and potential renal acid load was calculated. Bone-specific alkaline phosphatase was measured in serum samples collected on day 1 (immediately before bed rest) and on day 28. Potential renal acid load was higher in the AA group than in the Con group during bed rest (P < 0.05). For all subjects, during bed rest urinary NTX and DPD concentrations were greater than pre-bed rest levels (P < 0.05). Urinary NTX and DPD tended to be higher in the AA group (P = 0.073 and P = 0.056, respectively). During bed rest, urinary calcium was greater than baseline levels (P < 0.05) in the AA group but not the Con group. Total bone mineral content was lower after bed rest than before bed rest in the AA group but not the Con group (P < 0.05). During bed rest, urinary pH decreased (P < 0.05), and it was lower in the AA group than the Con group. These data suggest that bone resorption increased, without changes in bone formation, in the AA group.

Adult↗

The effects of simulated weightlessness on bone maturation.

In earlier studies we showed that elevating the hind limbs of growing rats for up to 2 weeks results in a temporary cessation of bone growth in the hind limbs and a transient fall in the serum levels of 1,25-dihydroxyvitamin D. To determine whether such skeletal unloading also retards the maturation of bone, as seen in vitamin D-deprived animals, we fractionated by density the tibiae from rats whose hind limbs had been elevated for up to 15 days. These fractions were analyzed for dry weight, calcium content, and calcium and proline uptake. The most dense fraction (fraction 4) had the highest degree of mineralization (ratio of calcium to dry weight) and comprised 82% of the total dry weight of the control tibiae. The total incorporation of [3H]proline administered in vivo 24 h before removing the tibiae was evenly distributed among all of the fractions, although it was highest in the least dense fraction (fraction 1) when normalized to dry weight. Total incorporation of 45Ca was highest in fraction 4, although when normalized to dry weight it was highest in fraction 3. With skeletal unloading, the proportions of bone and 45Ca incorporation in fraction 4 decreased, while the proportions in less dense fractions increased. [3H]Proline incorporation fell in all fractions. These effects were maximal after 10 days of unloading and returned toward the control values after that time. We conclude that skeletal unloading transiently reduced bone formation and retarded mineralization in the growing rat, which resulted in a decrease in mature bone.

Aging↗

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

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

Absorptiometry, Photon↗

Weightlessness and skeleton homeostasis.

As human beings venture into space in the 21st century, they will be confronted with a "hypodynamic" and thus hostile environment for the bone homeostasis, that could potentially compromise their mobility in general and skeletal strength in particular after landing. From this point of view, space flight studies are especially interesting and intriguing models for scientists. Space studies, however, must not only overcome enormous technical problems but are also limited in size and frequency. Therefore, ground-based models have also been developed to evaluate the effects of skeletal unloading. The most popular model for human studies is prolonged bed rest with normal volunteers, although studies with paraplegics have also been undertaken. In animals, the hindlimb elevation (tail suspension) model simulates space flight models and is well tolerated by the animals with minimal evidence of stress. Although negative calcium balance and bone loss have been observed in all the aforementioned models of skeletal unloading, the exact mechanism(s) by which this occurs are still unknown and mainly speculative.

Animals↗

Role of digitalis-like substance in the hypertension of streptozotocin-induced diabetes and simulated weightlessness in rats.

We have examined the role of plasma Na+-K+ pump inhibitor (SPI) in the hypertension of streptozotocin induced insulin dependent diabetes (IDDM) in reduced renal mass rats. The increase in blood pressure (BP) was associated with an increase in extracellular fluid volume (ECFV), and SPI and a decrease in myocardial Na+,K+ATPase (NKA) activity, suggesting that increased SPI, which inhibits cardiovascular muscle (CVM) cell NKA activity, may be involved in the mechanism of IDDM-hypertension. In a second study, using prolonged suspension resulted in a decrease in cardiac NKA activity, suggesting that cardiovascular deconditioning following space flight might in part result from insufficient SPI.

Animals↗

[The pharmacological correction of hemodynamics during the simulation of the early period of adaptation to weightlessness].

Investigations of volunteered subjects in whom antiorthostatic hypokinesia was modeled by tilting the cranial end of the body by -15 degrees were to answer whether pharmacological countermeasures of the vestibular/autonomous syndrome (motion sickness, sea sickness) alter the orthostatic tolerance and cardiovascular parameters. As was stated, the drugs allow controlled correction of hemodynamic resistance to the head-down tilt. Ephedrine, phencarol, ephedrine combined with scopolamine and pipolphen, and stugeron normalized cerebral circulation. Medicaments were unable to moderate the sympathoadrenal reaction to the head-down tilt; however, blood concentrations of catecholamines were significantly lower than in the control. The greatest effect was achieved using ephedrine and ephedrine plus pipolphen.

Adaptation, Physiological↗

[The inhibition of the thyroid and calcitonin-producing functions of the rat thyroid gland in weightlessness].

Histological, immunochemical and morphometric techniques were used to assess the functional activity of the thyroid parenchyma and calcitonin-producing C-cells of the thyroid gland (TG) in rats after 13 days on board Spacelab-2, in 5-6 hrs., and 14 days following the return from space flight. For the first time the fact of inhibition of the thyroid parenchyma and C-cells functioning during space flight was ascertained. Similarity of changes in the TG activity in and shortly after the space flight suggests that the morphological criteria used in 5 hrs. post flight give quite good insight into the character of changes occurring during microgravity. Two weeks of readaptation to the Earth's gravity result in recovery of the calcitonin production whereas the thyroid parenchyma displays postflight hyperactivity even after 14 days of return.

Animals↗

[Changes in the NO-dependent regulation of the local cerebral blood flow in rats during adaptation to the conditions of simulated weightlessness].

The nitrogen oxide NO-dependent regulation of the cerebral blood flow was studied before and after 24-hr head-down immobilization (HDI) of intact and pre-trained rats. Training consisted in 2-hr tail-suspension each day of the 2-wk period. Blood flow was determined with the laser Doppler flowmetry following local injection of a NO synthesis blocker (L-NAME), and NO (sodium nitroprusside). Neither HDI nor pre-training per se influenced NO tonic production in the cortex of large hemispheres and cerebellum. However, in pre-trained animals HDI resulted in a significant blood flow response to the local blockade of NO synthesis in the cerebellum. None of the animals changed the reaction of the blood flow to the local injection of sodium nitroprusside. The conclusion was drawn that alteration in the NO-dependent regulation of the brain blood flow in pre-trained animals could manifest of adaptation to HDI in the course of 24-hr suspension.

Adaptation, Physiological↗