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At least 145 records · Page 8

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DOE OSTI2022

Stress Drivers of Glucose Dynamics during Ozone Exposure Measured Using Radiotelemetry in Rats

Inhaled irritant air pollutants may trigger stress-related metabolic dysfunction associated with altered circulating adrenal-derived hormones. We used implantable telemetry in rats to assess real-time changes in circulating glucose during and after exposure to ozone and mechanistically linked responses to neuroendocrine stress hormones. First, using a cross-over design, we monitored glucose during ozone exposures (0.0, 0.2, 0.4, and 0.8 ppm) and nonexposure periods in male Wistar Kyoto rats implanted with glucose telemeters. A second cohort of unimplanted rats was exposed to ozone (0.0, 0.4 or 0.8 ppm) for 30 min, 1 h, 2 h, or 4 h with hormones measured immediately post exposure. We assessed glucose metabolism in sham and adrenalectomized rats, with or without supplementation of adrenergic/glucocorticoid receptor agonists, and in a separate cohort, antagonists. Ozone (0.8 ppm) was associated with significantly higher blood glucose and lower core body temperature beginning 90 min into exposure, with reversal of effects 4–6 h post exposure. Glucose monitoring during four daily 4-h ozone exposures revealed duration of glucose increases, adaptation, and diurnal variations. Ozone-induced glucose changes were preceded by higher levels of adrenocorticotropic hormone, corticosterone, and epinephrine but lower levels of thyroid-stimulating hormone, prolactin, and luteinizing hormones. Higher glucose and glucose intolerance were inhibited in rats that were adrenalectomized or treated with adrenergic plus glucocorticoid receptor antagonists but exacerbated by agonists. We demonstrated the temporality of neuroendocrine-stress–mediated biological sequalae responsible for ozone-induced glucose metabolic dysfunction and mechanism in a rodent model.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI2023

Differential transcriptomic alterations in nasal versus lung tissue of acrolein-exposed rats

Introduction: Acrolein is a significant component of anthropogenic and wildfire emissions, as well as cigarette smoke. Although acrolein primarily deposits in the upper respiratory tract upon inhalation, patterns of site-specific injury in nasal versus pulmonary tissues are not well characterized. This assessment is critical in the design of in vitro and in vivo studies performed for assessing health risk of irritant air pollutants. Methods: In this study, male and female Wistar-Kyoto rats were exposed nose-only to air or acrolein. Rats in the acrolein exposure group were exposed to incremental concentrations of acrolein (0, 0.1, 0.316, 1 ppm) for the first 30 min, followed by a 3.5 h exposure at 3.16 ppm. In the first cohort of male and female rats, nasal and bronchoalveolar lavage fluids were analyzed for markers of inflammation, and in a second cohort of males, nasal airway and left lung tissues were used for mRNA sequencing. Results: Protein leakage in nasal airways of acrolein-exposed rats was similar in both sexes; however, inflammatory cells and cytokine increases were more pronounced in males when compared to females. No consistent changes were noted in bronchoalveolar lavage fluid of males or females except for increases in total cells and IL-6. Acrolein-exposed male rats had 452 differentially expressed genes (DEGs) in nasal tissue versus only 95 in the lung. Pathway analysis of DEGs in the nose indicated acute phase response signaling, Nrf2-mediated oxidative stress, unfolded protein response, and other inflammatory pathways, whereas in the lung, xenobiotic metabolism pathways were changed. Genes associated with glucocorticoid and GPCR signaling were also changed in the nose but not in the lung. Discussion: These data provide insights into inhaled acrolein-mediated sex-specific injury/inflammation in the nasal and pulmonary airways. The transcriptional response in the nose reflects acrolein-induced acute oxidative and cytokine signaling changes, which might have implications for upper airway inflammatory disease susceptibility.

Alewel, Devin I.↗

NASA NTRS1978

Alterations in erythrocyte survival parameters in rats after 19.5 days aboard Cosmos 782

Rats were subjected to 19.5 days of weightless space flight aboard the Soviet biosatellite, Cosmos 782. Based on the output of CO-14, survival parameters of a cohort of erythrocytes labeled 15.5 days preflight were evaluated upon return from orbit. These were compared to vivarium control rats injected at the same time. Statistical evaluation indicates that all survival factors were altered by the space flight. The mean potential lifespan, which was 63.0 days in the control rats, was decreased to 59.0 days in the flight rats, and random hemolysis was increased three-fold in the flight rats. The measured size of the cohort was decreased, lending further support to the idea that hemolysis was accelerated during some portion of the flight. A number of factors that might be contributory to these changes are discussed, including forces associated with launch and reentry, atmospheric and environmental parameters, dietary factors, radiation, and weightlessness.

Leon, H. A.↗

NASA NTRS1978

Response of the iron-deficient erythrocyte in the rat to hyperoxia

Normal and iron-deficient rats were exposed to 90% O2 at 760 Torr for 24 or 48 h. Erythrocyte response to hyperoxia was monitored by potassium (rubidium) influx studies, by storage stress, and by ultrastructural studies. Normal rat erythrocytes exhibited morphological changes and decrease of ouabain-sensitive potassium influx compared to unexposed controls. Both components of erythrocyte potassium influx were affected by iron deficiency. Erythrocytes from unexposed iron-deficient rats showed a 50% increase in ouabain-sensitive potassium influx compared to controls. Iron-deficient rats exposed to hyperoxia for 24 or 48 h, had erythrocytes with morphological changes. Erythrocytes of iron-deficient rats exposed for 24 h showned no influx change; those exposed for 48 h showed a decrease of ouabain-sensitive influx compared to erythrocytes of controls.

Larkin, E. C.↗

NASA NTRS1980

Electroencephalographic changes in albino rats subjected to stress

Twenty one albino Wistar rats were subjected to stress for 7 hours. There was a significant difference in the slopes of regression lines for 7 nonulcerous rats and those for 14 ulcerous rats. Nonulcerous rats subjected to stress showed greater EEG curve synchronization than did ulcerous rats. If curve synchronization can be equated to a relaxed state, it may therefore be possible to explain the protective action of hypnotics, tranquilizers and analgesics on ulcers.

Mercier, J.↗

NASA NTRS1980

Insulin binding and glucose uptake of adipocytes in rats adapted to hypergravitational force

Rats were exposed to 4.15 g for 1 yr and weight and age matched, and lean noncentrifuged rats were used as control groups. Rats exposed to chronic hypergravity (hypergravic rats) were found to show lower ambient insulin levels, greater food intake with smaller body weight gain, and decreased size of isolated adipocytes. The ability of adipocytes from the hypergravic rats to bind insulin was increased. With Scatchard analysis, both number and affinity of receptors were increased. In contrast to the increased binding, glucose transport was found to be decreased in adipocytes from these animals. However, when the data were expressed as a percentage of maximal effect, the half maximal insulin effect for both the hypergravic and lean control groups was produced at an insulin concentration of 0.23 + or - 0.02 ng/ml, which was lower than the insulin concentration of 0.31 + or - 0.02 ng/ml for the weight-matched control group (P less than 0.05). This increased insulin sensitivity in the hypergravic group was accounted for by an increased number of receptors.

Kobayashi, M.↗

NASA NTRS1980

To develop behavioral tests of vestibular functioning in the Wistar rat

Two tests of vestibular functioning in the rat were developed. The first test was the water maze. In the water maze the rat does not have the normal proprioceptive feedback from its limbs to help it maintain its orientation, and must rely primarily on the sensory input from its visual and vestibular systems. By altering lighting conditions and visual cues the vestibular functioning without visual cues was assessed. Whether there was visual compensation for some vestibular dysfunction was determined. The second test measured vestibular functioning of the rat's behavior on a parallel swing. In this test the rat's postural adjustments while swinging on the swing with the otoliths being stimulated were assessed. Less success was achieved in developing the parallel swing as a test of vestibular functioning than with the water maze. The major problem was incorrect initial assumptions of what the rat's probable behavior on the parallel swing would be.

Nielson, H. C.↗

NASA NTRS1980

Effects of gravitational profiles on the rat's thermoregulatory response to cold

Unrestrained rats were subjected to a 1-h period of cold exposure during centrifugation to characterize their ability to regulate core temperature T(c) and to determine if this regulation was dependent on the amplitude of the hypergravic field before the cold exposure. T(c) was measured in unrestrained rats by the use of a thermistor implanted adjacent to the carotid artery. One hour of cold exposure applied over the last hour of either a 1-, 4-, 7-, 13-, 19-, 25-, or 37-h period at 3 G evoked a decrease in T(c) of about 3 C. This fall in T(c) was significantly greater than changes in T(c) in cold-exposed rats at 1 G. No significant differences were found between the measured decreases in T(c) observed for the 1-h cold exposures during the first 37 h at 3 G. However, when rats were subjected concurrently to cold and acceleration after eight days at 3 G, they exhibited a smaller fall in T(c) suggesting a partial recovery of the acceleration-induced impairment of temperature regulation. In another series of experiments, the gravitational field profile was changed in amplitude in three different ways during the 3-h period preceding the 1-h cold exposure at 3 G. Despite the different gravitational field profiles before cold, the magnitude of the fall in T(c) over the 1-h period of cold exposure was the same in all cases. These results suggest that the thermoregulatory impairment has a rapid onset, is a manifestation of an ongoing effect of hypergravity, and is not dependent on the prior G profile. The inability of rats to maintain T(c) when cold exposed may be transient as indicated by the partial recovery of regulation by the eighth day.

Schertel, E. R.↗

NASA NTRS1980

Effect of chronic intracerebroventricular angiotensin II infusion on vasopressin release in rats

The effects of the chronic infusion of angiotensin II into the lateral cerebral ventricle on the release of arginine vasopressin in rats are investigated. Rats were subjected to a continuous infusion of angiotensin at a rate of 1 microgram/h for five days, during which they were offered water, isotonic saline or hypertonic saline ad libitum or 40 ml water/day, and fluid intake, changes in body weight, plasma sodium ion concentrations and plasma and pituitary arginine vasopressin levels were measured. Angiotensin II is found to increase the fluid intake of rats given isotonic saline and decrease plasma sodium ion levels with no changes in plasma or pituitary arginine vasopressin in those given water or isotonic saline. However, in rats given hypertonic saline, plasma sodium concentrations remained at control levels while plasma vasopressin increased, and in water-restricted rats the effects of angiotensin II were intermediate. Results thus demonstrate that angiotensin II-stimulated arginine vasopressin release is reduced under conditions in which plasma sodium ion concentration becomes dilute, compatible with a central role of angiotensin in the regulation of salt and water balance.

Sterling, G. H.↗

NASA NTRS1982

Bone growth and composition in weanling and mature rats exposed to chronic centrifugation

The primary objective of the study is to determine the effect of continuous exposure to hypergravity on the development and composition of weight-bearing bone. The experimental results are seen to suggest that many, if not all, of the changes observed in bone growth and composition derive from the retarded growth rate of the centrifuged rats. Both centrifuged weanling and mature rats exhibit a significant reduction in femur length and mass. The changes in femur size are more apparent in the weanlings since they are exposed to hypergravity during their most rapid phase of skeletal development. In addition to a slower growth rate, the body mass of the mature and weanling animals is reduced even further by the depletion of body fat. The rapid loss of body fat observed in rats and mice during centrifugation, it is found, can produce a prompt and significant rise in relative femur mass after two weeks of exposure. After adaptation to centrifugation, however, relative femur mass is similar to that of controls at four and eight weeks. At 18 weeks, the centrifuged rats again exhibit an increase in relative femur mass. It is thought that this increase in relative femur mass may be generated by the difference in fat deposition between the 1-G controls and the high-G rats.

Keil, L. C.↗

NASA NTRS1982

Increased gluconeogenesis in hyper-G stressed rats

The role of gluconeogenesis in the altered carbohydrate metabolism in rats exposed to hyper-G stress is investigated. The blood levels of the substrates and hormones involved in gluconeogenesis were determined in rats exposed to 3.1 G for various time periods (0.25 to 24 hr). It is found that hyper-G stressed rats showed an immediate increase in plasma glucose at the onset of centrifugation which persisted throughout all the exposure periods. A substantial part of the initial rise in blood glucose is attributed to an increased rate of gluconeogenesis. An increase in liver glycogen deposition was observed in centrifuged rats as early as 0.50 hr exposure time, with progressively larger amounts accumulated as the exposure time was extended to 24 hr. It is concluded that the increase in gluconeogenic activity of hyper-G stressed rats is due to an increase in the mobilization of gluconeogenic substrates from perpheral tissues to the liver as a result of increases in circulating catecholamines and glucagon.

Daligcon, B. C.↗

NASA NTRS1983

Changes in total body calcium balance with exercise in the rat

The purpose of this study was to evaluate the effect of deconditioning on the total body calcium in rats. Two separate experiments were performed using female Sprague-Dawley rats, 187-266 days of age. Total body calcium was measured in experimental and control rats during and following several weeks of voluntary exercise. The slope from the least-squares fit of total body calcium with time was used to obtain an average calcium balance for each animal during each study period. In both groups, the exercised rats had a significantly decreased calcium balance after cessation of exercise, whereas no significant change was seen in nonexercised controls. In both groups, the exercised animals gained calcium at a significantly greater rate than controls. The findings indicate that while exercised rats may gain calcium at a faster rate compared with nonexercising controls, the rate of gain following cessation of exercise is less than in the controls.

Leblanc, A. D.↗

NASA NTRS1984

Tissue fluid shift, forelimb loading, and tail tension in tail-suspended rats

The tail suspension model (head-down tilt) simulates hypogravity in terms of musculoskeletal loss in the rat. However, little is known of tissue fluid shifts and body weight distribution in this model. Tissue fluid pressures were measured by wick catheters in 12 Munich-Wistar rats before, during, and after 48 hrs of tail suspension (about 30 deg head-down tilt). Subcutaneous tissue fluid pressure in the neck increased from -2.2 + or - 0.4 (normal horizontal position) to +4.0 + or - 1.5 cm H2O during tail suspension, indicating a cephalic fluid shift and significant edema during head-down tilt. In a separate study, six rats were suspended at 30-70 deg, and forelimb load and tail tension were measured by a balance and force transducer, respectively. Approximately 50 percent of body weight (BW) was loaded on forelimbs at a head-down tilt angle of 30 deg and forelimb load declined linearly to 10 percent BW at 70 deg. Furthermore, tail tension increased from 50 percent BW at 30 deg to 85 percent BW at 70 deg. These results indicate that less than normal loads are applied to forelimbs of rats suspended at angles of less than 30 deg and that the tail bears an increasing proportion of the rat's body weight at head-down tilt angles of less than 30 deg.

Hargens, A. R.↗

NASA NTRS1984

Thymic involution in the suspended rat model for weightlessness - Decreased glucocorticoid receptor concentration

Hindlimb muscle atrophy, thymic involution and adrenal hypertrophy in rats during spaceflight can be simulated using suspension models. Skeletal muscle and thymus are sensitive to gluco-corticoids (GC), and previous studies have demonstrated that muscle atrophy in suspended rats is associated with increased GC receptor concentration. The objectives were to confirm thymic involution during suspension, and determine if involution correlated with increased GC receptor concentration. Seven days of antiorthostatic (AO) suspension of rats produced a significant (P less than 0.001) reduction in thymic wet weight not associated with an alteration of percent water content. GC receptor concentration (pmol/mg protein) decreased 20 percent (P less than 0.025) in thymus glands from 7 day AO suspended rats. Suspension, therefore, is associated with involution of the thymus, but this is not dependent upon AO positioning. Thymus GC receptor concentrations were depressed in 7-day suspended rats, in contrast with previous observations on skeletal muscle, suggesting that different mechanisms may underlie these responses.

Steffen, J. M.↗

NASA NTRS1985

Effect of flight in mission SL-3 on interferon-gamma production by rats

Rats flown in Space Shuttle mission SL-3 were sacrificed after flight and spleens were removed. Cultures of spleen cells were challenged with the mitogen concanavalin-A to attempt to induce interferon-gamma. Most control, ground-based rats had spleen cells that produced moderate titers of interferon-gamma. Spleen cells from flown rats did not produce interferon-gamma in most cases, and one flown rat produced minimally detectable amounts of interferon. These data suggest that interferon-gamma production was inhibited in rats flown in mission SL-3 immediately upon return to earth.

Gould, C. L.↗

NASA NTRS1989

Decreased swelling pressure of rat nucleus pulposus associated with simulated weightlessness

Data are presented on the effects of actual and simulated weightlessness on the swelling pressure of nucleus pulposus in rats exposed to 12.5 days of flight aboard Cosmos 1887 or to seven days of tail suspension, respectively. The flight-exposed rats were adapted to normal gravity for over 50 hrs prior to sacrifice and tissue harvesting. In the experiments with flight-exposed rats, swelling pressures were 690, 675, and 622 mm Hg for flight rats, synchronous controls, and vivarium controls, respectively. In experiments with simulated weightlessness, swelling pressures were 295, 610, and 527 mm Hg for tail-suspended rats, cage controls, and vivarium controls, respectively, suggesting that fluid moves into the disc during seven days of simulated weightlessness.

Hargens, Alan R.↗

NASA NTRS1989

Effects of simulated weightlessness and sympathectomy on maximum VO2 of male rats

The effects of simulated weightlessness (hind-limb suspension) and chemical sympathectomy (by repeated injections with guanethidine sulfate) on the maximum oxygen consumption (VO2 max) of female rats were investigated in rats assigned for 14 days to one of three groups: a head-down hind-limb suspension, a horizontal suspension with hind limbs weight bearing, or the caged control. The VO2 max values were assessed by having rats run on a treadmill enclosed in an airtight chamber. The hind-limb-suspended sympathectomized rats were found to exhibit shorter run times and lower mechanical efficiencies, compared to their presuspension values or the values from saline-injected suspended controls. On the other hand, the suspended sympathectomized rats did not demonstrate a decrease in the VO2 max values that was observed in saline-injected controls.

Woodman, C. R.↗

NASA NTRS1992

Effects of insulin and exercise on rat hindlimb muscles after simulated microgravity

The effect of simulated microgravity on the insulin- and exercise-stimulated glucose uptake and metabolism in the hindlimb muscles of rats was investigated using three groups of rats suspended at 45 head-down tilt (SUS) for 14 days: (1) cage control, (2) exercising (treadmill running) control, and (3) rats subjected to suspension followed by exercise (SUS-E). It was found that the suspension of rats with hindlimbs non-weight bearing led to enhanced muscle responses to insulin and exercise, when these stimuli were applied separately. However, the insulin affect appeared to be impaired after exercise for the SUS-E rats, especially for the soleus muscle.

Stump, Craig S.↗