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Rats exposed to simulated conditions of microgravity exhibit reductions in aerobic exercise capacity that may be due to an impaired ability of the sympathetic nervous system (SNS) to mediate an increase in cardiac output and to redistribute blood flow. The purpose of this study was to quantify the sympathetic response to exercise in rats after exposure to 14 days of simulated microgravity or control conditions. To achieve this aim, rats were exposed to 14 days of head-down suspension (HDS) or cage control (CC) conditions. On day 14, norepinephrine (NE) synthesis was blocked with alpha-methyl-p-tyrosine, and the rate of NE depletion after synthesis blockade was used to estimate SNS activity in the left ventricle, spleen, and soleus muscle during treadmill exercise at 75% of maximal oxygen uptake. When compared with CC rats, the sympathetic response to exercise in HDS rats was characterized by a lower rate of NE depletion in the left ventricle (-82%) and spleen (-42%). The rate of NE depletion in the soleus muscle was 47% higher. These differences could contribute to the decrement in aerobic capacity of HDS rats by impairing their ability to augment cardiac output and to redirect blood flow to actively contracting skeletal muscle during exercise.

Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

Rats exposed to simulated conditions of microgravity by head-down suspension (HDS) exhibit reductions in aerobic capacity. This may be due to an impaired ability to augment cardiac output and to redistribute blood flow during exercise. The purpose of this investigation was to measure cardiac output and blood flow distribution in rats that were exposed to 14 days of HDS or cage control conditions. Measurements were obtained at rest and during light-intensity (15 m/min) and heavy-intensity (25 m/min; 10% grade) treadmill exercise. Cardiac output was similar in HDS and cage control rats at rest and light exercise but was significantly lower in HDS rats (-33%) during heavy exercise. Soleus muscle blood flow (ml/min) was lower at rest and during exercise in HDS rats; however, when expressed relative to muscle mass (ml.min-1.100 g-1), soleus blood flow was lower only during light exercise. Plantaris muscle blood flow was lower in HDS rats during heavy exercise. Blood flow to the ankle flexor, knee extensor, and knee flexor muscles was not altered by HDS. Blood flow to the spleen and kidney was significantly higher in HDS rats. It was concluded that the reduction in aerobic capacity associated with HDS is due in part to an impaired ability to augment cardiac output during exercise.

Rats exposed to head-down suspension (HDS) exhibit reductions in maximal O2 consumption (VO2max) and atrophy of select hindlimb muscles. This study tested the hypothesis that an endocrine-deficient rat exposed to HDS would not exhibit reductions in VO2max or hindlimb muscle mass. Hypophysectomized (HYPX) and sham-operated (SHAM) rats were tested for VO2max before and after 28 days of HDS or cage control (CC) conditions. No significant reductions in VO2max were observed in HYPX rats. In contrast, SHAM-HDS rats exhibited a significant reduction in absolute (-16%) and relative (-29%) measures of aerobic capacity. Time course experiments revealed a reduction in VO2max in SHAM-HDS rats within 7 days, suggesting that cardiovascular adjustments to HDS occurred in the 1st wk. HDS was associated with atrophy of the soleus (-42%) in SHAM rats, whereas HYPX rats exhibited atrophy of the soleus (-36%) and plantaris (-13%). SHAM-HDS rats had significantly lower (-38%) soleus citrate synthase activities per gram muscle mass than SHAM-CC, but no significant differences existed between HYPX-HDS and -CC rats. HDS rats had an impaired ability to thermoregulate, as indicated by significantly greater temperature increases per unit run time, compared with their CC counterparts. Pretreatment plasma epinephrine levels were significantly lower in HYPX than in SHAM rats. Norepinephrine concentration was similar for all groups except HYPX-HDS, in which it was significantly higher. HDS had no significant effect on thyroxine or triiodothyronine. SHAM-HDS rats had significantly lower concentrations of testosterone and growth hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to examine the effect of non-weight-bearing conditions and the systemic influences of simulated microgravity on rat hindlimb muscles. For this purpose, rats were suspended (SUS) in a head-down position (45 degrees) with the left hindlimb non-weight bearing (NWB) and the right hindlimb bearing 20% of presuspension body mass (WB). Weight bearing by the SUS-WB limb was accomplished by using a platform connected to a rod in sleeve, cable, and pulley apparatus to which weight could be added. Rats (250-325 g) were assigned to SUS or cage control (CC) conditions for 14 days. The angle between the foot and leg for SUS-WB and CC remained similar (20-30 degrees) throughout the experiment while the SUS-NWB hindlimbs extended to approximately 140 degrees by day 12. On day 14, the soleus, plantaris, and gastrocnemius muscles from the SUS-NWB limbs exhibited significantly lower (P < or = 0.05) masses than presuspension mass values (29, 11, and 21%, respectively). Weight bearing by the SUS-WB limbs prevented the loss of mass by these muscles. In separate groups of SUS and CC rats, 2-deoxyglucose uptake during hindlimb perfusion was significantly higher in both SUS-NWB and SUS-WB hindlimbs at 24,000 microU/ml of insulin compared with CC for all the muscles examined (21-80%). In addition, extracellular space (ml/g) was significantly greater in the soleus muscles from both the SUS-NWB and SUS-WB hindlimbs (64%) compared with CC muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Head-down suspension (HDS) of rats has evolved as a useful model for the simulation of a microgravity environment. Previous HDS experiments with rats have shown an impaired capacity to perform aerobic exercise as demonstrated by reductions in maximum oxygen consumption (VO2 max), treadmill run time (RT), and mechanical efficiency (ME) of treadmill running at submaximal conditions. To determine whether endurance training (TR) before HDS would modify exercise performance, male Sprague-Dawley rats were assigned to nontrained (NT) or TR groups for 6 wk and exposed to HDS or cage control (CC) conditions for 29 days. The rats were tested for VO2 max, RT, and ME before treatment and on days 7, 14, 21, and 28. In addition, water and electrolyte excretion was measured on days 1 and 21 of the experimental period. Before HDS, the TR rats had significantly higher measures of VO2 max (15%) and RT (22%) than the NT rats. On day 28, HDS was associated with significant reductions in absolute VO2 max (ml/min) in TR (-30%) and NT (-14%) rats. Relative VO2 max (ml.min-1.kg-1) was significantly reduced in TR (-15%) but not NT rats. Similar reductions in RT occurred in TR (-37%) and NT (-35%) rats by day 28. ME was reduced 22% in both TR and NT rats after 28 days of suspension. HDS elicited diuresis, natriuresis, and kaliuresis in TR rats after 21 days but not after 24 h. In contrast, HDS-NT rats exhibited no diuretic, natriuretic, or kaliuretic responses.(ABSTRACT TRUNCATED AT 250 WORDS)

This study was designed to examine insulin- and exercise-stimulated glucose uptake and metabolism in the hindlimb muscles of rats after conditions of simulated microgravity. To simulate microgravity, male Sprague-Dawley rats were suspended in a head-down (45 degrees) position with their hindlimbs non-weight bearing (SUS) for 14 days. In addition, rats were assigned to suspension followed by exercise (SUS-E), to cage control (CC), or to exercising control (CC-E) groups. Exercise consisted of five 10-min bouts of treadmill running at the same relative intensity for the CC-E and SUS-E rats (80-90% of maximum O2 consumption). Hindlimb perfusion results indicated that glucose uptake for the entire hindquarter at 24,000 microU/ml insulin (maximum stimulation) was significantly higher in the SUS (8.9 +/- 0.5 mumol.g-1.h-1) than in the CC (7.6 +/- 0.4 mumol.g-1.h-1) rats, signifying an increased insulin responsiveness. Glucose uptake at 90 microU/ml insulin was also significantly higher in the SUS (48 +/- 4; % of maximum stimulation over basal) than in the CC (21 +/- 4%) rats. In addition, exercise-induced increases in glucose uptake for the hindlimbs (133%) and glucose incorporation into glycogen for the plantaris (8.4-fold), extensor digitorum longus (5.4-fold), and white gastrocnemius (4.8-fold) muscles were greater for the SUS-E rats than for the CC-E rats (39% and 1.9-, 1.9-, and 3.0-fold, respectively). Therefore, suspension of the rat with hindlimbs non-weight bearing leads to enhanced muscle responses to insulin and exercise when they were applied separately. However, insulin action appeared to be impaired after exercise for the SUS-E rats, especially for the soleus muscle.

Maximum oxygen consumption (VO2max) has been shown to be reduced after periods of simulated weightlessness. To assess the role of the sympathetic nervous system in these reductions, Sprague-Dawley rats were either chemically sympathectomized (SYMX) or injected with saline (SHAM) and assigned to head-down suspension (HDS), horizontal restraint with the hindlimbs weight bearing (HWB), or cage-control (CC) conditions. VO2max, run time (RT), and mechanical efficiency (ME) were measured before suspension and on days 7 and 14. Male and female SHAM HDS groups exhibited reduced measures of VO2max (12-13%) after 7 and 14 days, and this decrease was attenuated in the SYMX and HWB rats. HDS resulted in a significant reduction in RT (9-15%) in both the male and female rats, and ME was significantly reduced after HDS in male and female SYMX and male SHAM rats (23-33%) but not in the female SHAM rats. Lesser reductions in ME were observed in the HWB rats. HDS and HWB were associated with lower body, fat-free, and fat masses, which were similar in male and female rats as well as for the SHAM and SYMX conditions. In a related HDS experiment with normal rats, plasma norepinephrine and epinephrine were increased by 53 and 42% after 7 days, but only epinephrine returned to baseline after 14 days. It was concluded that chemical sympathectomy and/or a weight-bearing stimulus will attenuate the loss in VO2max associated with simulated weightlessness in rats despite similar changes in body mass and composition. The mechanism(s) remains unclear at this time.

Mature male rats (n = 16) were assigned to either 14 days of head-down suspension with one hindlimb supported (HDS) or to control cages (C) of similar dimensions. Hindlimb support during HDS preserved the muscle mass-to-body mass ratio (mg/100g) compared with C conditions for the soleus (48.3 +/- 1.0 to 41.7 +/- 1.0), plantaris (98.4 +/- 3.4 to 103.3 +/- 4.1), and gastrocnemius (484.7 +/- 18.5 to 507.2 +/- 13.9). However, the muscle mass-to-body mass ratio was significantly lower for the soleus (28.9 +/- 1.5), plantaris (83.9 +/- 3.6), and gastrocnemius (411.9 +/- 24.2) muscles from the freely hanging hindlimbs compared with the contralateral muscles from the supported hindlimbs or muscles from C animals. Citrate synthase activity (mumol.g-1.min-1) was significantly lower in soleus muscles from HDS rats in both the supported (19.4 +/- 2.3) and freely hanging (20.0 +/- 1.6) hindlimbs compared with C (28.5 +/- 3.1), whereas soleus muscle glycogen concentration (mg/g) was significantly higher in the freely hanging limbs from HDS rats (5.90 +/- 0.31) but not in the supported limbs (3.80 +/- 0.61) compared with C (4.34 +/- 0.50). Doppler flow probes were used to determine that iliac blood flow to freely hanging hindlimbs was significantly decreased after 48 (-19 +/- 5%) and 72 (-20 +/- 6%)h of HDS compared with presuspension values. In addition, iliac vascular resistance was significantly elevated at most time points during the 72 h of HDS in the freely hanging limbs but not the supported hindlimbs.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether hindlimb suspension is associated with the development of cardiovascular deconditioning, male rats were studied before and after undergoing one of three treatment conditions for 9 days: 1) cage control (n = 15, CON), 2) horizontal suspension (n = 15, HOZ), and 3) head-down suspension (n = 18, HDS). Testing included lower body negative pressure administered during chloralose-urethan anesthesia and graded doses of sympathomimetic agents (norepinephrine, phenylephrine, and tyramine) administered to conscious unrestrained animals. Both HDS and HOZ were associated with a small decrease in the hypotensive response to lower body negative pressure. The HOZ group, but not the HDS group, exhibited augmented reflex tachycardia. Furthermore, both HDS and HOZ groups manifested reduced pressor responses to phenylephrine after treatment. These reductions were associated with significantly attenuated increases in mesenteric vascular resistance. However, baroreflex control of heart rate was not altered by the treatment conditions. Collectively, these results indicate that 9 days of HDS in rats does not elicit hemodynamic response patterns generally associated with cardiovascular deconditioning induced by hypogravic conditions.

Male rodents were studied before and after undergoing one of three treatment conditions for 9 days: 1) cage control (n = 15, CON), 2) horizontal suspension (n = 15, HOZ), and 3) head-down suspension (n = 18, HDT). Testing included measurements of maximal O2 uptake (VO2 max) and select cardiovascular responses to graded treadmill exercise. VO2 max expressed on an absolute basis (ml/min) was significantly decreased after HOZ (-14.1 +/- 2.5%) and HDT (-14.3 +/- 2.0%), while being essentially unchanged in CON (-1.0 +/- 3.3%). Significant reductions in body weight were observed after both HOZ (-10.1 +/- 4.2 g) and HDT (-22.5 +/- 3.3 g), whereas CON animals exhibited a significant increase in weight (10.4 +/- 3.8 g). As a result, when VO2 max was normalized for body weight, all groups exhibited similar significant reductions of 6-7%. Although no differences in heart rate and blood pressure response to graded exercise were observed, the HDT group exhibited greater increases in mesenteric resistance at the same absolute exercise intensity. Furthermore, both suspended groups had higher iliac resistance values during exercise at similar relative exercise conditions, suggesting that muscle blood flow during treadmill running may have been reduced after suspension. In general, the decrements associated with the HOZ and HDT conditions were similar. It was concluded that reduction in exercise capacity and altered cardiovascular responses to exercise observed after 6-9 days of suspension were attributable to a combination of hypokinesia, lack of hindlimb weight bearing, or restraint, rather than to hydrostatic influences associated with HDT.

Head-down tilt is considered an effective experimental model to simulate weightlessness. To determine the acute effects of simulated weightlessness on transcapillary fluid balance, tissue fluid shifts, muscle function, and triceps surae reflex time, eight supine subjects were tilted 5 degrees head down for 8 h. A cephalic fluid shift from the legs was indicated by facial edema, nasal congestion, increased urine flow, decreased creatinine excretion, reduced calf girth, and decreased lower leg volume. As measured by wick catheters inserted under local anesthesia, interstitial fluid pressure in the tibialis anterior muscle (4.6 +/- 0.6 mmHg) and subcutaneous tissue (0.6 +/- 0.5 mmHg) of the lower leg fell significantly to -2.8 +/- 0.5 and -3.8 +/- 0.4 mmHg, respectively. Other transcapillary pressures (capillary and interstitial fluid colloid osmotic pressures) were relatively unchanged. Needle-biopsy specimens, obtained just before and after tilt, indicated that total water content of soleus muscle was unchanged during 8 h of head-down tilt. After head-down tilt, isometric strength and isokinetic strength of the plantar flexors were unchanged. Triceps surae reflex time associated with plantar flexion movement slowed slightly after the tilt maneuver. Collectively these results demonstrated a dehydration effect of head-down tilt on muscle and subcutaneous tissues of the lower leg that may affect muscle function.

The launching of the shuttle in 1981 initiated a new era in the space age. In spite of the more than 20 yr of experience and research on the anatomical and physiological effects of weightlessness, problems remain. The resolution of these problems requires countermeasures, of which exercise deserves to be considered. The uncertainty concerning the importance of exercise has evolved, in part, because of the limited number of subjects studied, the paucity of controlled experimental designs, the inability to follow standardized routines in a space environment, and the lack of specificity in the exercises prescribed. Exercise has the potential to be an effective countermeasure for the decreases in bone density, fluid volumes, muscle mass, muscular strength, orthostatic tolerance, cardiovascular deconditioning, and submaximal exercise performances that occur in a O-gravity environment if aerobic training is minimized, maximum isometric and power-type exercises are emphasized, and circuit-training principles utilized. Because the majority of future space flights will last 21 d or less, the majority of future studies on the role of exercise should concentrate on that time period.