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Biomedical subjects

C E Wade

Publications and source records attributed to C E Wade.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prolonged fasting increases the response of the renin-angiotensin-aldosterone system, but not vasopressin levels, in postweaned northern elephant seal pups.

The 8- to 12-week postweaning fast exhibited by northern elephant seal pups (Mirounga angustirostris) occurs without any apparent deleterious effects on fluid and electrolyte homeostasis. However, during the fast the role of vasopressin (AVP) has been shown to be inconclusive and the involvement of the renin-angiotensin-aldosterone system (RAAS) has yet to be examined. To examine the effects of prolonged fasting on these osmoregulatory hormones, 15 postweaned pups were serially blood-sampled during the first 49 days of their fast. Fasting did not induce significant changes in ionic or osmotic concentrations, suggesting electrolyte homeostasis. Total proteins were reduced by day 21 of fasting and remained depressed, suggesting a lack of dehydration. Aldosterone and plasma renin activity exhibited a correlated, linear increase over the first 49 days of the fast, suggesting an active RAAS. Aldosterone exhibited a parabolic trend over the fast with a peak at day 35, suggesting a shift in the sensitivity of the kidney to aldosterone later in the fast. AVP was elevated at day 49 only, but concentrations were relatively low. RAAS was modified during the postweaning fast in pups and appears to play a significant role in the regulation of electrolyte and, most likely, water homeostasis during this period.

Aldosterone↗
PubMed2000

Effects of acute fresh water exposure on water flux rates and osmotic responses in Kemp's ridley sea turtles (Lepidochelys kempi).

Water flux rates and osmotic responses of Kemp's Ridley sea turtles (Lepidochelys kempi) acutely exposed to fresh water were quantified. Salt-water adapted turtles were exposed to fresh water for 4 d before being returned to salt water. During the initial salt water phase, absolute and relative water flux rates were 1.2+/-0.1 l d(-1) and 123.0+/-6.8 ml kg(-1) d(-1), respectively. When turtles were exposed to fresh water, rates increased by approximately 30%. Upon return to salt water, rates decreased to original levels. Plasma osmolality, Na(+), K(+), and Cl(-) decreased during exposure to fresh water, and subsequently increased during the return to salt water. The Na(+):K(+) ratio was elevated during the fresh water phase and subsequently decreased upon return to salt water. Aldosterone and corticosterone were not altered during exposure to fresh water. Elevated water flux rates during fresh water exposure reflected an increase in water consumption, resulting in a decrease in ionic and osmotic concentrations. The lack of a change in adrenocorticoids to acute fresh water exposure suggests that adrenal responsiveness to an hypo-osmotic environment may be delayed in marine turtles when compared to marine mammals.

Adaptation, Physiological↗
PubMed2000

Urinary excretion of LH and testosterone from male rats during exposure to increased gravity: post-spaceflight and centrifugation.

A dissociation between plasma luteinizing hormone (LH) and testosterone (T) appears to exist during exposure to altered gravity. The pulsatile nature of LH release and the diurnal variability of T secretion may mask or bias the effects of altered gravity on the pituitary-gonadal axis when analyzing plasma concentrations. Therefore, we examined the relationship between the excretion of urinary LH and T in male Sprague-Dawley rats during exposure to increased gravity upon return to Earth following a 14-day spaceflight (n = 6) and by 12 days of centrifugation at 2g (n = 8). Excreted LH and T were elevated on the first 3 days postflight. Excreted T was elevated between Days 1 and 8 of centrifugation; however, excreted LH was reduced on Days 2 and 3 compared with control animals. Excreted LH and T were significantly correlated (R = 0.731 and 0.706, respectively) in postspaceflight and centrifuged animals. Correlation curves had similar slopes (0.0213 and 0.023, respectively), but different y-intercepts (-1.43 and 3.32, respectively). The sustained increase in excreted T during centrifugation suggests that the pituitary-gonadal axis in postspaceflight animals may adapt quicker to increased gravity. The upward shift in the correlation curve exhibited by the centrifuged animals suggests that the sensitivity of LH-induced T release is increased in these animals. The previous dissociation between plasma LH and T during altered gravity was not observed in the present study in which excreted LH and T were measured.

Adaptation, Physiological↗
PubMed2000

Renal vasopressin receptor expression and function in rats following spaceflight.

It has been suggested there is a decreased renal responsiveness to vasopressin following spaceflight and that this may be the mechanism for the increased urine flow that is observed following return to normal gravity. In the present study, we have therefore measured vasopressin receptor expression and activity in kidneys taken from rats 1 and 14 days following spaceflight of 15 days duration. Measurements of renal vasopressin V(2) and V(1a) receptor mRNA expression by quantitative RT-PCR demonstrated little difference at either 1 day or at 14 days following return from space. Evaluation of (3)H-labeled arginine vasopressin binding to membranes prepared from kidneys indicated that the majority of the vasopressin receptors were V(2) receptors. Furthermore, the data suggested that binding to vasopressin V(2) or V(1a) receptors was unaltered at 1 day and 14 days following spaceflight. Similarly, the ability of vasopressin to stimulate adenylate cyclase suggested no change in vasopressin V(2) receptor activity in these animals. These data suggest that, whatever changes in fluid and electrolyte metabolism are observed following spaceflight, they are not mediated by changes in vasopressin receptor number or vasopressin-induced stimulation of adenylate cyclase.

Animals↗
PubMed2000

Water balance in rats exposed to chronic centrifugation.

Changes in gravitational load have been shown to alter renal function, which could potentially affect water balance. Therefore, the present study was conducted to determine the effects of chronic centrifugation on water balance. Eight Sprague-Dawley rats were centrifuged (12 days at 2 G), and eight rats were used as a control group. Water balance over the course of the study was determined by quantifying the percentage (%) of total body water [TBW; (TBW/body mass)] and water flux (water consumption - urine volume). TBW was estimated, by means of deuterium oxide dilution, before the study and after 3 days of centrifugation and by means of desiccation after 12 days of centrifugation. %TBW did not change in the centrifuged rats from initial levels or relative to controls over the course of the study. Differences between the sum of water consumption and sum of urine volume for the 12-day period were the same in both groups. Although an initial period of negative water balance was observed, the lack of a change in %TBW among the three measurement periods or in water flux over the 12 days of centrifugation suggests that water balance is not negatively affected as a result of centrifugation at 2 G.

Animals↗
PubMed2000

Renal responsiveness to aldosterone during exposure to simulated microgravity.

We measured renal functions and hormones associated with fluid regulation after a bolus injection of aldosterone (Ald) during head-down tilt (HDT) bed rest to test the hypothesis that exposure to simulated microgravity altered renal responsiveness to Ald. Six male rhesus monkeys underwent two experimental conditions (HDT and control, 72 h each) with each condition separated by 9 days of ambulatory activities to produce a crossover counterbalance design. One test condition was continuous exposure to 10 degrees HDT; the second was a control, defined as 16 h per day of 80 degrees head-up tilt and 8 h prone. After 72 h of exposure to either test condition, monkeys were moved to the prone position, and we measured the following parameters for 4 h after injection of 1-mg dose of Ald: urine volume rate (UVR); renal Na(+)/K(+) excretion ratio; renal clearances of creatinine, Na(+), osmolality, and free water; and circulating hormones [Ald, renin activity (PRA), vasopressin (AVP), and atrial natriuretic peptide (ANP)]. HDT increased Na(+) clearance, total renal Na(+) excretion, urine Na(+) concentration, and fractional Na(+) excretion, compared with the control condition, but did not alter plasma concentrations of Ald, PRA, and AVP. Administration of Ald did not alter UVR, creatinine clearance, Ald, PRA, AVP, or ANP but reduced Na(+) clearance, total renal Na(+) excretion, urinary Na(+)/K(+) ratio, and osmotic clearance. Although reductions in Na(+) clearance and excretion due to Ald were greater during HDT than during control, the differential (i.e., interaction) effect was minimal between experimental conditions. Our data suggest that exposure to microgravity increases renal excretion of Na(+) by a natriuretic mechanism other than a change in renal responsiveness to Ald.

Aldosterone↗
PubMed2000

Rat growth, body composition, and renal function during 30 days increased ambient CO2 exposure.

BACKGROUND: In experiments using rodents onboard orbiting spacecraft, specimens may be exposed to an increase in ambient CO2. HYPOTHESIS: Many of the physiological changes reported in rats (and humans) for spaceflight are similar to those observed with increased CO2, raising the question whether the observed changes are due to spaceflight or more specifically, the elevated ambient CO2. METHODS: To evaluate the effects of increased CO2, at levels similar to those experienced during spaceflight, three groups of adult male rats (n = 10) were exposed to ambient CO2 concentrations of 0.3, 0.7 and 2.0% for 30 d. Control rats were exposed to atmospheric conditions (0.03% CO2) for each group. RESULTS: There were alterations in water turnover, food intake, and renal function with increased CO2. Blood pH, total CO2, and plasma concentrations of Na+, Ca2+, and corticosterone were significantly elevated at the 2.0% exposure, while plasma PO4(3-) was reduced. At the 0.3% and 0.7% CO2 exposures, many of these changes were not significant. Animals exposed to 0.3% CO2 showed a significant increase in total body Na+. Urinary Ca2+, K+, creatinine, corticosterone, and total CO2 excretion were higher at 2.0%, but only Ca2+ and CO2 excretion were significantly elevated at 0.7%, and there was no significant alteration in renal function at 0.3%. CONCLUSION: Chronic increased ambient CO2 levels, similar to those observed on the Space Shuttle and proposed for the International Space Station, elicit compensatory responses in rats which may affect interpretation of experiments designed to evaluate the effects of exposure to microgravity.

Acid-Base Equilibrium↗
PubMed2000

Effects of hindlimb suspension and elevated ambient CO2 on rat growth and renal function.

BACKGROUND: Previous studies show that an ambient CO2 concentration of 2.0% may complicate interpretation of animal experiments conducted in spaceflight, while 0.7% CO2 exposure produces minimal effects. HYPOTHESIS: With additional spaceflight factors, such as microgravity, effects from the 0.7% CO2 exposure may be amplified. METHODS: To investigate the combined effects from microgravity and elevated CO2 on growth and renal function, two groups of rats were hindlimb suspended for 37 d, and a third group served as an ambulatory vivarium control (AMB). One suspension group was exposed to 0.7% CO2 for 30 d (HLS + 0.7% CO2), while the other group (HLS) served as a suspended control. Both the AMB and HLS groups breathed room air at 0.03% CO2. RESULTS: The HLS group showed responses consistent with past hindlimb suspension studies when compared with AMB, indicating similar reductions in organ and tissue weights and body weight gain. When comparing HLS + 0.7% CO2 animals to HLS controls, exposure to CO2 revealed lowered food consumption and increased urine volume, NH3 and CO2 excretion, with no differences in any of the other measured parameters, such as body weight gain, pH values, or electrolyte handling. CONCLUSION: This study shows that chronic exposure to both 0.7% ambient CO2 and hindlimb suspension together have little additional effect on rat growth and renal function.

Air Pollution, Indoor↗
PubMed2000

Increases in body mass of rats during spaceflight: models and measurements.

To test the hypothesis that the body mass of rats is increased during spaceflight, we developed two models from the literature and obtained mass measurements during spaceflight. From studies of centrifugation (hypergravity), there is a reduction in body mass of rats dependent on the exposure gravity level. From data in 18 publications on rats subjected to hypergravity by centrifugation, we developed a model that predicted a 27% increase in body mass during the microgravity of spaceflight. Following spaceflight, with an increase in gravity on return to Earth, there is a reduction in body mass of rats for over 3 d. We related the reduction in body mass after spaceflight to the time after landing that mass measurements were made. From data in 23 publications on rats returning from spaceflight, we developed a model that predicted a 19% increase in body mass during spaceflight. Measurement of body mass of rats on days 6 and 10 of spaceflight found a 7 and 9% increase compared with ground control animals. The increase in body mass during spaceflight suggests that the rat may provide a viable model for metabolic studies in which changes during spaceflight may be predicted in part by ground-based hypergravity studies.

Analysis of Variance↗
PubMed2000

Survival and growth of developing rats during centrifugation at 2G.

We studied the effects of 2G hypergravity on the survival, body mass and growth of postnatal rats (Rattus norvegicus). Nursing litters comprised of either neonatal (Postnatal day [P]7) or pre-weanling (P14) rats and their mothers were exposed to 16 days of continuous centrifugation. All of the offspring survived and gained body mass, indicating that mothers nursed their young. Following the onset of centrifugation, neonatal and pre-weanling rats showed a reduction in growth relative to age-matched environmental controls (EC). At the completion of testing, body mass of the hypergravity (HG) groups was significantly less than that of controls (p<0.05). Over the course of the test, the HG-exposed P7 group showed an overall 55% gain in body mass as compared to a 71% increase in controls, while the HG-exposed P14 group showed a 62% increase relative to 75% in controls. Neonatal offspring (P7) gained body mass during centrifugation, but at significantly slower rates as compared to EC controls (p<0.05). In contrast, growth rates of pre-weanling (P14) rats were not reduced relative to controls, possibly related to the initiation of weaning, around P18 in the rat. These findings raise key issues relevant to studies of nursing mammals reared in altered gravity.

Age Factors↗
PubMed2000

Renal responsiveness to aldosterone during exposure to head-down tilt bedrest.

The kidneys represent a fundamental organ system responsible in part for the control of vascular volume. A 10% to 20% reduction in plasma volume is one of the fundamental adaptations during exposure to low gravity environments such as bedrest and space flight. Bedrest-induced hypovolemia has been associated with acute diuresis and natriuresis. Elevated baseline plasma renin activity and aldosterone levels have been observed in human subjects following exposure to head-down tilt and spaceflight without alterations in renal sodium excretion. Further, attempts to restore plasma volume with isotonic fluid drinking or infusion in human subjects exposed to head-down bedrest have failed. One explanation for these observations is that renal distal tubular cells may become less sensitive to aldosterone following exposure to head-down tilt, with a subsequent reduction in renal capacity for sodium retention. We hypothesized that elevated sodium and water excretion observed during prolonged exposure to bedrest and the subsequent inability to restore body fluids by drinking might be reflected, at least in part, by reduced renal tubular responsiveness to aldosterone. If renal tubular responsiveness to aldosterone were reduced with confinement to bedrest, then we would expect measures of renal sodium retention to be reduced when a bolus of aldosterone was administered in head-down tilt (HDT) bedrest compared to a control experimental condition. In order to test this hypothesis, we conducted an investigation in which we administered an acute bolus of aldosterone (stimulus) and measured responses in renal functions that included renal clearances of sodium and free water, sodium/potassium ratio in urine, urine sodium concentration, and total and fractional renal sodium excretion.

Aldosterone↗
PubMed1999

Influence of centrifugation and hindlimb suspension on testosterone and corticosterone excretion in rats.

BACKGROUND: Alterations in mass loading have been shown to stimulate the pituitary-gonadal and pituitary-adrenal axes resulting in changes in testosterone (T) and corticosterone (B) production which may account for the previously reported variations in muscle mass under these conditions. HYPOTHESIS: Centrifugation and hindlimb suspension will induce opposing effects on testosterone and corticosterone excretion. METHODS: Effects of mass loading (centrifugation at -2Gx) and unloading (hindlimb suspension, HLS) on excreted T and B levels, and testicular mass were examined in Sprague-Dawley rats. For 12 d, 16 (8 controls and 8 centrifuged) rats and 20 (10 unsuspended controls and 10 suspended) rats were studied during the centrifugation and suspension portions of the study, respectively. Following the completion of each study, testicular mass was measured. RESULTS: Absolute testicular mass was not different, following 12 d of centrifugation. Excreted T was elevated between days 1 and 6 of centrifugation. Excreted B levels were elevated for the first 4 d of centrifugation. Suspension reduced absolute and relative testicular mass. Excreted T levels were reduced from days 3-12 of suspension, while excreted B levels were only elevated on the first day of suspension. CONCLUSIONS: Centrifugation stimulated an increase in T excretion despite a lack of a change in absolute testicular mass. Conversely, suspension resulted in a reduction in T excretion which may have been associated with a decrease in absolute testicular mass. The centrifugation-induced increase in T excretion is consistent with previously reported increases in lean body mass following centrifugation, while the HLS-induced reduction in T excretion correlates with previously reported decreases in lean body mass following suspension.

Adrenal Glands↗
PubMed1999

Urea and osmotic excretion in rats exposed to chronic centrifugation.

BACKGROUND: A reduction in vasopressin was attributed to the initial diuresis reported in rats exposed to chronic centrifugation. However, it was suggested that urea may also contribute an osmotic component to this observed diuresis. HYPOTHESIS: Increased urea excretion will contribute to osmotic excretion during chronic centrifugation, which may be partly responsible for the initial diuresis previously observed. METHODS: Eight Sprague-Dawley rats were centrifuged (12 d at -2Gx) and eight were used as a control group. Daily urine samples were collected and an aliquot measured for excreted solutes and aldosterone. RESULTS: Urine volume was elevated over the first 7 d of centrifugation with a peak on day 4. Urea and osmotic excretion were elevated over the first 5 d. Excreted Na+ was elevated on days 1 and 2, which coincided with an increase in excreted aldosterone over the first 3 d of centrifugation. Urea excretion accounted for up to 54% of the increase in osmotic excretion during the initial portion of centrifugation suggesting that urea was, in part, responsible for the observed increase in urine output despite a reduction in water consumption. Following the first day of centrifugation, aldosterone appears to regulate Na+ as suggested by the reduction in Na+ excretion between days 2 and 3 when aldosterone excretion was elevated. CONCLUSIONS: It would appear that centrifugation induced an acute increase in protein catabolism as indicated by the increase in urea excretion which resulted in an increase in obligatory water loss. This increased diuresis may have acute consequences on the hydration state of centrifuged rats.

Aldosterone↗
PubMed1999

Alterations in the volume stimulus-renal response relationship during exposure to simulated microgravity.

We measured central venous pressure (CVP), plasma volume (PV), urine volume rate (UVR), and circulating hormones (renin activity (PRA), vasopressin (AVP), atrial natriuretic peptide (ANP), and cortisol) before and after acute volume infusion (Dextran-40) to test the hypotheses that head-down tilt bedrest (HDT) caused (1) a resetting of the CVP operating point and (2) attenuated urine excretion. Six rhesus monkeys underwent two experimental conditions (HDT and control, each of 48 hour duration) with each condition separated by nine days of ambulatory activities to produce a cross-over counterbalance design. One test condition was continuous exposure to 10 degrees HDT and the second test condition was a control, defined as approximately 12-14 hours per day of 80 degrees head-up tilt and 10-12 hours prone. Following 48 hours of exposure to either test condition, 20-minute continuous infusion of Dextran-40 was administered. CVP in HDT was lower than the control condition. Similar elevations in CVP occurred 30 min post-infusion in both test conditions, and returned to pre-infusion baseline levels between 22 and 46 h post-infusion in both treatments. The UVR response during infusion was attenuated by HDT despite similar elevation in CVP. Elevation in ANP and reduction in PRA at the end of infusion were greater in Control compared to HDT. No differences between control and HDT were detected for AVP and cortisol responses to infusion. Since CVP returned to its pre-infusion levels following volume loading in HDT and control conditions, it appeared that the lower CVP may reflect a new operating point about which vascular volume is regulated. Further, attenuated ANP and PRA responses during vascular volume loading may contribute to depressed UVR in low gravity exposure.

Animals↗
PubMed1999

Deposition and renal handling of urinary electrolytes from rats during spaceflight.

To study renal handling of urinary electrolytes from male Fisher 344 rats during spaceflight, waste pads were obtained from cages flown in space and from cages used for ground controls. Pads were obtained from cages in which animals were group-housed (n=6 animals/cage) (Animal Enclosure Module; AEM) for 12 days or individually housed (2 animals/divided cage) (Research Animal Holding Facility; RAHF) for 19 days. Pads were washed, and extracts analyzed for sodium, potassium, chloride, calcium, and creatinine concentrations. It was observed that spaceflight reduced the absolute concentrations of electrolytes deposited onto the pads. When adjustments were made for deposition on all cage surfaces during flight, electrolyte and creatinine concentrations were similar to those of controls. Specifically, there were no differences in the sodium-, potassium-, and chloride-to-creatinine ratios of flight and control animals, suggesting no difference in the renal handling of these electrolytes during spaceflight. The calcium-to-creatinine ratio of urine on flight waste pads was reduced, suggesting an increase in reabsorption. From these analyses, the renal handling of sodium, potassium, and chloride does not appear to be altered in rats during spaceflight, while that of calcium may be. Deposition of urine on all surfaces of the cages during spaceflight should be considered in the design of future animal habitats, and in future analyses of waste pad constituents.

Animals↗
PubMed1998

Hemodynamic and metabolic responses to repeated hemorrhage and resuscitation with hypertonic saline dextran in conscious swine.

Previous work in our laboratory has demonstrated that HSD is an effective small-volume resuscitation fluid for the treatment of hemorrhagic hypotension, but limitations to its usefulness in severe hemorrhage have not been explored. In the present study, animals (N = 12) were bled from an arterial line at a rate of 1 mL/kg/min until continuously monitored aortic blood flow was reduced to one-half its baseline value, and then they were immediately resuscitated with 7.5% NaCl/6% dextran 70 (hypertonic saline dextran, 4 mL/kg) administered intravenously over 3 min. After recording the maximum improvement in blood pressure, blood samples were obtained and the hemorrhage-resuscitation sequence was repeated until no further measurable increase in cardiac index or blood pressure could be elicited by resuscitation. In the majority of the animals, cardiac index and right and left ventricular stroke work could be improved at least through two bleedings and resuscitation. These improvements sufficed to increase oxygen delivery and consumption, despite the decreases in hematocrit induced by bleeding, transcapillary refill, and asanguinous fluid administration. Under these severe hemorrhage conditions, the acid-base imbalance was not improved by hypertonic saline dextran, and the rate of increase in acidosis was not affected by its administration. We observed a progressive decrease in base excess from +1.35+/-3.19 (mean +/- standard error) to -12.9+/-2.1 mEq/L even when resuscitation improved oxygen consumption significantly by 95+/-20%. In animals that survived as many as three bleedings and resuscitation, the depletion of buffering capacity of the blood was most predominant, and bicarbonate reached a nadir of 7.62 mEq/L with a base excess of -22.4 mEq/L. It is evident that restoration of perfusion in shock treats only a portion of the physiologic dysfunction, leaving major metabolic derangements uncorrected.

Acid-Base Equilibrium↗