Acute Hypoxia Tolerance Research Articles

Comparative analysis of glucose and fructose tolerance in two marine fishes: effects on insulin secretion and acute hypoxia tolerance

Carbohydrates are a common and economical energy source in animal feeds. However, most fish show a persistent postprandial hyperglycemia after intake of a high-carbohydrate diet. Unfortunately, the mechanism of glucose metabolism in fish is still unclear. In the present study, tiger puffer (Takifugu rubripes) and turbot (Scophthalmus maximus) were intraperitoneally injected or orally administered with glucose or fructose (500 mg/kg body weight) to evaluate the ability of fish to utilize carbohydrates. Afterwards, serum glucose, fructose, pyruvate, insulin levels, and acute hypoxia tolerance were measured. Our results showed increased serum glucose level and then decreased post intraperitoneal injection with glucose, and reached a peak after 0.5 hours in turbot and 1 hour in tiger puffer. Tiger puffer had significantly lower liver glycogen, serum glucose, fructose, pyruvate, and insulin contents than turbot. Glucose and fructose only induced insulin secretion in turbot, but did not change serum insulin level in tiger puffer. Glucose was a stronger stimulator of insulin than fructose in the two marine species. Both intraperitoneal injection and oral fructose intake increased serum glucose level, while intraperitoneal or oral glucose also increased serum fructose level. Intraperitoneal injection of glucose promoted absorption and utilization of glucose in the blood more effectively than oral glucose intake. In addition, turbot and tiger puffer were intolerant to acute hypoxia, whereas supplementation with glucose or fructose improved hypoxia tolerance in the two marine fishes by activating anaerobic glycolysis. Taken together, our results provide important scientific information for understanding the mechanism for glucose and fructose utilization and improving hypoxia tolerance in fish.

Metabolites and gene expression in the myocardium of fasting rats in an acute hypoxic environment

With the rising demand for entry to extremely high altitudes (HAs), rapid adaptability to extremely hypoxic environments is a challenge that we need to explore. Fasting was used to evaluate acute hypoxia tolerance at HA and was proven to be an effective method for improving the survival rate at extreme HA. Our experiments also showed that fasting pretreatment for 72 h significantly increased the 24 h survival rate of rats at 7620 m from 10 to 85% and protected the myocardium cells of rats. Here, we compared the metabolites and gene expression in the myocardium of SD rats pretreated with fasting and nonfasting at normal altitude and extreme HA. Our findings demonstrated that the dynamic contents of detected differential metabolites (DMs) between different rat groups were consistent with the expression of differentially expressed genes (DEGs), and DM clusters also showed strong correlations with DEG clusters. DM clusters related to amino acids and lipids were significantly lower in the fasting groups, and the correlated DEG clusters were enriched in mitotic pathways, including CDK1, CDC7, NUF2, and MCM6, suggesting that fasting can attenuate mitotic processes in cardiac tissues and reduce the synthesis of amino acids and lipids. L-Glutamine-related metabolites were particularly low at extreme HA without pretreatment but were normal in the fasting groups. The DEGs in the cluster related to L-glutamine-related metabolites were enriched for T-cell receptor V(D)J recombination, the Hippo signaling pathway, the Wnt signaling pathway, the cGMP-PKG signaling pathway, and the mTOR signaling pathway and were significantly downregulated, indicating that the content of L-glutamine decreased at extreme HA, while fasting increased it to adapt to the environment. Moreover, abundant fatty acids were detected when rats were exposed to extreme HA without pretreatment. Our study revealed the fasting and hypoxic environment-related factors in SD rats and provided new insights into the genetic and molecular characteristics in the myocardium, which is critical to developing more potential rapid adaptation methods to extreme HA.

Genome-wide association study and genomic prediction of tolerance to acute hypoxia in rainbow trout

Hypoxia is one of the major threats to the aquaculture sector resulting in substantial economic losses to the fish farmers. Thus, tolerance to hypoxia is of high economic interest to be genetically improved by breeding programs. Rainbow trout (Oncorhynchus mykiss) is one of the most cultured salmonid species worldwide, with well-developed breeding programs. Still, studies of genetic potential to improve hypoxia tolerance in this species are rare. In the present study, 1320 individuals of rainbow trout were used for a genome-wide association study of acute hypoxia tolerance based on imputed high-density genotypes to explore the genetic architecture and related candidate genes affecting hypoxia response. Three significant (Omy31_1, Omy31_2, Omy20) and two putative (Omy15, Omy28) quantitative trait loci (QTLs) were detected, but each of them only explained between 0.2% and 0.8% of the genetic variance of acute hypoxia tolerance. However, heritability was estimated at a moderate value of 0.24–0.28, that suggests a solid potential to improve hypoxia tolerance in the studied rainbow trout population by genetic selection. Moreover, it was shown that genomic prediction for hypoxia tolerance would lead to a relative increase of ∼11% for genomic selection (GS) accuracy compared to the pedigree-based selection, considering a reference population of 1000 individuals. Finally, fifteen genes (ids, fmr1, arx, lonrf3, commd5, map4k4, smu1, b4galt1, re1, abca1, noa1, igfbp7, noxo1, bcl2a, mylk3) were proposed as potential functional candidates involved in hypoxia tolerance. Taking all proposed candidate genes (6 out of 15 genes) and high linkage disequilibrium (r2) values within the main QTL (Omy31_1), we may hypothesize that the complex response to acute hypoxia in rainbow trout, i.e., the interplay between behavioural, morphological, and physiological responses, is primarily encoded by a supergene. However, further functional validation of their effects may help to specify the biological mechanisms triggering a response to acute hypoxia in rainbow trout.

The interplay between prior selection, mild intermittent exposure, and acute severe exposure in phenotypic and transcriptional response to hypoxia.

Hypoxia has profound and diverse effects on aerobic organisms, disrupting oxidative phosphorylation and activating several protective pathways. Predictions have been made that exposure to mild intermittent hypoxia may be protective against more severe exposure and may extend lifespan. Here we report the lifespan effects of chronic, mild, intermittent hypoxia, and short‐term survival in acute severe hypoxia in four clones of Daphnia magna originating from either permanent or intermittent habitats. We test the hypothesis that acclimation to chronic mild intermittent hypoxia can extend lifespan through activation of antioxidant and stress‐tolerance pathways and increase survival in acute severe hypoxia through activation of oxygen transport and storage proteins and adjustment to carbohydrate metabolism. Unexpectedly, we show that chronic hypoxia extended the lifespan in the two clones originating from intermittent habitats but had the opposite effect in the two clones from permanent habitats, which also showed lower tolerance to acute hypoxia. Exposure to chronic hypoxia did not protect against acute hypoxia; to the contrary, Daphnia from the chronic hypoxia treatment had lower acute hypoxia tolerance than normoxic controls. Few transcripts changed their abundance in response to the chronic hypoxia treatment in any of the clones. After 12 h of acute hypoxia treatment, the transcriptional response was more pronounced, with numerous protein‐coding genes with functionality in oxygen transport, mitochondrial and respiratory metabolism, and gluconeogenesis, showing upregulation. While clones from intermittent habitats showed somewhat stronger differential expression in response to acute hypoxia than those from permanent habitats, contrary to predictions, there were no significant hypoxia‐by‐habitat of origin or chronic‐by‐acute treatment interactions. GO enrichment analysis revealed a possible hypoxia tolerance role by accelerating the molting cycle and regulating neuron survival through upregulation of cuticular proteins and neurotrophins, respectively.

Fasting improves tolerance to acute hypoxia in rats

Acute high-altitude illness seriously threatens the health and lives of people who rapidly ascend to high altitudes, but there is currently no particularly effective method for the prevention or treatment of acute high-altitude illness. In the present study, we found that fasting preconditioning effectively improved the survival rate of rats exposed to a simulated altitude of 7620 m for 24 h, and a novel animal model of rapid adaptation to acute hypoxia was established. Compared with control treatment, fasting preconditioning activated AMPK, induced autophagy, decreased ROS levels, and inhibited NF-κB signaling in the cardiac tissues of rats. Our results suggested that fasting effectively improved the acute hypoxia tolerance of rats, which was gradually enhanced with prolongation of fasting. In addition, the acute hypoxia tolerance of young rats was significantly higher than that of adult rats. These experimental results lay the foundation for achieving rapid adaptation to acute hypoxia in humans.

Histopathological, hematological, and biochemical changes in high-latitude fish Phoxinus lagowskii exposed to hypoxia.

Hypoxia is one of the most significant threats to biodiversity in aquatic systems. The ability of high-latitude fish to tolerate hypoxia with histological and physiological responses is mostly unknown. We address this knowledge gap by investigating the effects of exposures to different oxygen levels using Phoxinus lagowskii (a high-latitude, cold-water fish) as a model. Fish were exposed to different oxygen levels (0.5 mg/L and 3 mg/L) for 24 h. The loss of equilibrium (LOE), an indicator of acute hypoxia tolerance, was 0.21 ± 0.01 mg/L, revealing the ability of fish to tolerate low-oxygen conditions. We sought to determine if, in P. lagowskii, the histology of gills and liver, blood indicators, enzyme activities of carbohydrate and lipid metabolism, and antioxidants changed to relieve stress in response to acute hypoxia. Notably, changes in vigorous jumping behavior under low oxygen revealed the exceptional hypoxia acclimation response compared with other low-latitude fish. A decrease in blood parameters, including RBC, WBC, and Hb, as well as an increase in MCV was observed compared to the controls. The increased total area in lamella and decreased ILCM volume in P. lagowskii gills were detected in the present study. Our results also showed the size of vacuoles in the livers of the hypoxic fish shrunk. Interestingly, an increase in the enzyme activity of lipid metabolism but not glucose metabolism was observed in the groups exposed to hypoxia at 6 h and 24 h. After combining histology and physiology results, our findings provide evidence that lipid metabolism plays a crucial role in enhancing hypoxia acclimation in P. lagowskii. Additionally, SOD activity significantly increased during hypoxia, suggesting the presence of an antioxidant response of P. lagowskii during hypoxia. High expression levels of lipogenesis and lipolysis-related genes were detected in the 6 h 3 mg/L and 24 h 3 mg/L hypoxia group. Enhanced expression of lipid-metabolism genes (ALS4, PGC-1, and FASN) was detected during hypoxia exposure. Together, these data suggest that P. lagowskii's ability to tolerate hypoxic events is likely mediated by a comprehensive strategy.

Hydrogen peroxide treatment of Atlantic salmon temporarily decreases oxygen consumption but has negligible effects on hypoxia tolerance and aerobic performance

Hydrogen peroxide is widely used as a treatment of ectoparasite (e.g. salmon lice, amoebic gill disease) affected Atlantic salmon (Salmo salar) in aquaculture but has frequently caused unacceptable levels of mortality. Hydrogen peroxide toxicity increases with dose, exposure duration and temperature, and can cause an acute stress response, oxidative stress, gill damage, respiratory acidosis and altered gas and ion exchange. The combined stress effects have the potential to cause sub-lethal impacts on aerobic capacity that affects hypoxia tolerance and swimming performance. Here, we tested the sub-lethal effects of hydrogen peroxide treatment on the aerobic capacity, hypoxia tolerance and gill histopathology of healthy Atlantic salmon. Hydrogen peroxide treatment (1250 ppm at 12 °C for 20 min) caused a significant but negligible reduction in acute hypoxia tolerance (lost equilibrium at slightly higher levels of dissolved oxygen) immediately following treatment, but not in the 14 days afterwards. Immediately following hydrogen peroxide treatment (1250 ppm at 16 °C for 20 min) oxygen consumption was reduced for up to 20 min in normoxia and 40 min in hypoxia. However, following transient reductions in oxygen consumption the maximum metabolic rate and Ucrit measured in a swim flume were unaffected by hydrogen peroxide exposure (1250 ppm at 16 °C). Resting metabolic rate was unaffected by hydrogen peroxide treatment in all experiments. Hydrogen peroxide exposure caused non-homogenous lamellar epithelium lifting with subepithelial oedema and multi-focal lamellar fusion. The reduction in oxygen consumption following hydrogen peroxide treatment was likely caused by an increase in blood oxygen due to the breakdown of hydrogen peroxide by catalase and other oxidative enzymes in the fish tissues. Ultimately, hydrogen peroxide did not affect aerobic performance and had negligible impacts on hypoxia tolerance, suggesting that hydrogen peroxide has minimal sub-lethal impacts on aerobic performance of healthy Atlantic salmon at the doses used here.

Acute measures of upper thermal and hypoxia tolerance are not reliable predictors of mortality following environmental challenges in rainbow trout (Oncorhynchus mykiss).

Anthropogenic climate change threatens freshwater biodiversity and poses a challenge for fisheries management, as fish will increasingly be exposed to episodes of high temperature and low oxygen (hypoxia). Here, we examine the extent of variation in tolerance of acute exposure to these stressors within and among five strains of rainbow trout (Oncorhynchus mykiss) currently being used or under consideration for use in stocking programmes in British Columbia, Canada. We used incipient lethal oxygen saturation (ILOS) as an index of acute hypoxia tolerance, critical thermal maximum (CTmax) as an index of acute upper thermal tolerance and mortality following these two acute exposure trials to assess the relative resilience of individuals and strains to climate change-relevant stressors. We measured tolerance across two brood years and two life stages (fry and yearling), using a highly replicated design with hundreds of individuals per strain and life stage. There was substantial within-strain variation in CTmax and ILOS, but differences among strains, although statistically significant, were small. In contrast, there were large differences in post-trial mortality among strains, ranging from less than 2% mortality in the most resilient strain to 55% mortality in the least resilient. There was a statistically significant, but weak, correlation between CTmax and ILOS at both life stages for some strains, with thermally tolerant individuals tending to be hypoxia tolerant. These data indicate that alternative metrics of tolerance may result in different conclusions regarding resilience to climate change stressors, which has important implications for stocking and management decisions for fish conservation in a changing climate.

Reduced hypoxia tolerance and survival at elevated temperatures may limit the ability of Amazonian fishes to survive in a warming world

The Amazon basin contains more than 20% of the world's freshwater fishes, many of ecological and economical importance. An increase in temperature of 2.2 to 7 °C is predicted to occur within the next century in the worst-case scenario of climate change predictions, which will likely be associated with an increase in the prevalence and duration of reduced water oxygen levels (hypoxia). Furthermore, there is an increasing frequency of heat waves in the Amazon basin, which exacerbates issues related to temperature and hypoxia. Increases in temperature and hypoxia both constrain an organism's ability to supply oxygen to metabolizing tissues, thus the ability to cope with thermal and hypoxic stress may be correlated. Here, we reveal a positive correlation between acute thermal tolerance and acute hypoxia tolerance amongst 37 Amazonian fish species at the current river temperatures of 28–31 °C. The effects of long-term (10 days or 4 weeks) increases in temperature were investigated in a subset of 13 species and demonstrated that 2 species failed to acclimate and survive at 33 °C, 9 species failed at 35 °C, and only 2 species survived up to 35 °C. Of those that survived long-term exposure to 33 or 35 °C, the majority of the species demonstrated only an improvement in acute thermal tolerance. In contrast, hypoxia tolerance was reduced following acute- and long-term exposure to 33, 35 or 37 °C in all species investigated. The results of this study suggest that many of the fish species that inhabit the Amazon may be at risk during both short- and long-term temperature increases and these risks are exacerbated by the associated environmental hypoxia.

Sublethal exposure to copper supresses the ability to acclimate to hypoxia in a model fish species

Hypoxia is one of the major threats to biodiversity in aquatic systems. The association of hypoxia with nutrient-rich effluent input into aquatic systems results in scenarios where hypoxic waters could be contaminated with a wide range of chemicals, including metals. Despite this, little is known about the ability of fish to respond to hypoxia when exposures occur in the presence of environmental toxicants. We address this knowledge gap by investigating the effects of exposures to different levels of oxygen in the presence or absence of copper using the three-spined sticklebacks (Gasterosteus aculeatus) model. Fish were exposed to different air saturations (AS; 100%, 75% and 50%) in combination with copper (20 μg/L) over a 4 day period. The critical oxygen level (Pcrit), an indicator of acute hypoxia tolerance, was 54.64 ± 2.51% AS under control conditions, and 36.21 ± 2.14% when fish were chronically exposed to hypoxia (50% AS) for 4 days, revealing the ability of fish to acclimate to low oxygen conditions. Importantly, the additional exposure to copper (20 μg/L) prevented this improvement in Pcrit, impairing hypoxia acclimation. In addition, an increase in ventilation rate was observed for combined copper and hypoxia exposure, compared to the single stressors or the controls. Interestingly, in the groups exposed to copper, a large increase in variation in the measured Pcrit was observed between individuals, both under normoxic and hypoxic conditions. This variation, if observed in wild populations, may lead to selection for a tolerant phenotype and alterations in the gene pool of the populations, with consequences for their sustainability. Our findings provide strong evidence that copper reduces the capacity of fish to respond to hypoxia by preventing acclimation and will inform predictions of the consequences of global increases of hypoxia in water systems affected by other pollutants worldwide.

Hypoxia during incubation does not affect aerobic performance or haematology of Atlantic salmon (Salmo salar) when re-exposed in later life.

Hypoxia in aquatic ecosystems is becoming increasingly prevalent, potentially reducing fish performance and survival by limiting the oxygen available for aerobic activities. Hypoxia is a challenge for conserving and managing fish populations and demands a better understanding of the short- and long-term impacts of hypoxic environments on fish performance. Fish acclimate to hypoxia via a variety of short- and long-term physiological modifications in an attempt to maintain aerobic performance. In particular, hypoxia exposure during early development may result in enduring cardio-respiratory modifications that affect future hypoxia acclimation capacity, yet this possibility remains poorly investigated. We incubated Atlantic salmon (Salmo salar) in normoxia (~100% dissolved oxygen [DO, as percent air saturation]), moderate hypoxia (~63% DO) or cyclical hypoxia (100–25% DO daily) from fertilization until 113 days post-fertilization prior to rearing all groups in normoxia for a further 8 months. At ~11 months of age, subsets of each group were acclimated to hypoxia (50% DO) for up to 44 days prior to haematology, aerobic metabolic rate and hypoxia tolerance measurements. Hypoxia exposure during incubation (fertilization to 113 days post-fertilization) did not affect the haematology, aerobic performance or hypoxia tolerance of juvenile salmon in later life. Juveniles acclimated to hypoxia increased maximum aerobic metabolic rate and aerobic scope by ~23 and ~52%, respectively, when measured at 50% DO but not at 100% DO. Hypoxia-incubated juveniles also increased haematocrit and haemoglobin concentration but did not affect acute hypoxia tolerance (critical oxygen level and DO at LOE). Thus, while Atlantic salmon possess a considerable capacity to physiologically acclimate to hypoxia by improving aerobic performance in low oxygen conditions, we found no evidence that this capacity is influenced by early-life hypoxia exposure.

How does chronic temperature exposure affect hypoxia tolerance in sheepshead minnows' (Cyprinodon variegatus variegatus) ability to tolerate oxidative stress?

Estuarine environments are characterized by cyclical fluctuations in tides, with tidal shifts drastically, frequently, and acutely altering temperature, dissolved oxygen, and salinity. Despite these ecological challenges, the sheepshead minnow, Cyprinodon variegatus, seems to dominate estuarine landscapes. Here, we held sheepshead minnows to four temperature treatment groups for 1month. We then tested whether temperature exposure had an effect on acute hypoxia tolerance via oxidative stress. We measured superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, as well as total antioxidant capacity and lipid peroxidation (LPO) damage in white muscle. We found that exposure to increasing temperatures (15, 20, 25, and 30°C) for 1month led to significantly higher CTmax in sheepshead minnows. We also found that CAT activity significantly increased in the 20 and 25°C temperature treatment groups, whereas it did not change between control and hypoxia trials. SOD activity was significantly higher in control groups of the 15 and 30°C temperature treatment groups compared with hypoxia groups of these same temperature treatments. GPx activity was significantly lower in the 30°C temperature treatment group regardless of control or hypoxia trials. Hydroxyl scavenging capacity varied across temperature treatment and control/hypoxia groups. Peroxyl scavenging capacity and LPO damage showed no significant differences across temperature treatment groups or between control and hypoxia trials.

Metabolic and locomotor responses of juvenile paddlefish Polyodon spathula to hypoxia and temperature

Hypoxia is an increasing problem in the natural habitats that the paddlefish (Polyodon spathula) has historically inhabited, and a potential problem in managed culture conditions. However, the effects of hypoxia on paddlefish are not well understood. In order to understand the effects of hypoxia on juvenile paddlefish, acute hypoxia tolerance, aerobic metabolic rates and swimming capabilities were measured under normoxic (PO2=140–155mm Hg) and hypoxic (PO2=62–70mm Hg) conditions at 18°C and 26°C. The results showed that paddlefish acclimated to 18°C and 26°C had routine metabolic rates of 211mg/kg/h and 294mg/kg/h, respectively, with a corresponding Q10 of 1.5. At 18°C and 26°C, paddlefish had a critical partial pressure of oxygen (PO2crit) of 74mm Hg and 89mm Hg, respectively. Paddlefish had a lethal oxygen threshold of 31.0mm Hg and 37.0mm Hg at 18°C and 26°C, respectively. Further, paddlefish exhibited a reduction in swimming capability when exposed to hypoxia with a 24% and 41% decrease in Ucrit at 18°C and 26°C, respectively. Therefore, paddlefish are relatively sensitive to hypoxia, and at temperatures from 18 to 26°C require a dissolved oxygen concentration ≥4.7mg/L to maintain basal aerobic metabolism and >2.0mg/L to survive under acute hypoxia.

Dietary taurine can improve the hypoxia-tolerance but not the growth performance in juvenile grass carp Ctenopharyngodon idellus

This study was conducted to evaluate the effects of dietary taurine, as a feed additive, on the hypoxia-tolerance and growth performance of the juvenile grass carp Ctenopharyngodon idellus, one of the most important and intensively cultured freshwater fish, with the largest production in China. Graded levels of taurine (0, 0.5, 1, 1.5, 2 and 2.5 g kg(-1) dry diet) were fed to grass carp juveniles (mean weight: 5.26 ± 0.03 g) for 8 weeks. The survival time during acute hypoxia increased as dietary levels of taurine increased, with the highest dose of taurine resulting in the best acute hypoxia-tolerance. The erythrocyte osmotic fragility in grass carp was significantly improved when dietary taurine level was at least 1.5 g kg(-1) diet and can be improved much more when dietary taurine level was up to 2.5 g kg(-1) diet. A significant correlation between hemolysis rate of the erythrocyte osmotic fragility test and the survival time of acute hypoxia (r = -0.873, P = 0.023 < 0.05) strongly suggested that the biomembrane stabilization function of taurine may contribute to its role of enhancing acute hypoxia-tolerance in grass carp. Dietary taurine cannot improve growth performance of grass carp, but it can increase the value of mesenteric fat index, indicating that dietary taurine influences the lipid metabolism. This study provides valuable information to improve hypoxia-tolerance of grass carp.

The effect of hypoxia on intermediary metabolism and oxidative status in gilthead sea bream (Sparus aurata) fed on diets supplemented with methionine and white tea

The present study evaluates the influence of previous nutritional status, fish fed on diets supplemented with tea and methionine, on acute hypoxia tolerance and subsequent recovery of Sparus aurata juveniles. Four isonitrogenous (45% of protein) and isolipidic (18% lipid) diets were formulated to contain 0.3% methionine, 2.9% white tea dry leaves or 2.9% of white tea dry leaves+0.3% methionine. An unsupplemented diet was used as control. Hepatic key enzymes of intermediary metabolism and antioxidant status, superoxide dismutase isoenzyme profile, glutathione (total, reduced and oxidized) and oxidative damage markers were determined under normoxia, hypoxia challenge and during normoxia recovery. Dietary white tea inclusion decreased plasma glucose levels under normoxia and seemed to induce an increase in anaerobic pathways as showed by enhanced liver lactate dehydrogenase activity. Hypoxia challenge reversed some of the responses induced by diet tea supplementation. Hypoxia decreased plasma glucose levels, increased glucose 6-P-dehydrogeanse activity, decreased superoxide dismutase activity (especially Mn-SOD and CuZn-SOD isoforms) and increased glutathione peroxidase activity in all dietary treatments. Catalase activity during hypoxia varied with dietary treatments and glutathione reductase was not modified. Antioxidant defenses were insufficient to avoid an oxidative stress condition under hypoxia, independently of dietary treatment. In general, pre-challenge values were recovered for almost all parameters within 6h recovery time.

Metabolomic and flux‐balance analysis of age‐related decline of hypoxia tolerance inDrosophilamuscle tissue

The fruitfly Drosophila melanogaster is increasingly used as a model organism for studying acute hypoxia tolerance and for studying aging, but the interactions between these two factors are not well known. Here we show that hypoxia tolerance degrades with age in post-hypoxic recovery of whole-body movement, heart rate and ATP content. We previously used 1H NMR metabolomics and a constraint-based model of ATP-generating metabolism to discover the end products of hypoxic metabolism in flies and generate hypotheses for the biological mechanisms. We expand the reactions in the model using tissue- and age-specific microarray data from the literature, and then examine metabolomic profiles of thoraxes after 4 h at 0.5% O2 and after 5 min of recovery in 40- versus 3-day-old flies. Model simulations were constrained to fluxes calculated from these data. Simulations suggest that the decreased ATP production during reoxygenation seen in aging flies can be attributed to reduced recovery of mitochondrial respiration pathways and concomitant overdependence on the acetate production pathway as an energy source.

Chronic hypobaric hypoxia induces tolerance to acute hypoxia and up-regulation in alpha-2 adrenoceptor in rat locus coeruleus

Hypoxia preconditioning has been shown to produce tolerance against brain injuries. The hypothesis of this study is that chronic hypobaric hypoxia may also induce acute hypoxia tolerance. We used intracellular recording in slices from rats exposed to chronic hypobaric hypoxia (exposed) and control to investigate the effects of chronic hypobaric hypoxia on the physiology of locus coeruleus (LC) including neuronal excitability. The results showed 35.7% reduced spontaneous firing rate and no change for membrane potential and input resistance in exposed neurons. In response to the alpha-2 adrenoceptor (A2R) agonist clonidine, both the hyperpolarizing potency and efficacy were increased indicated by a decreased EC50 (control: 30.9 nM and exposed: 19.7 nM) and a 50.5% increase in maximum hyperpolarized potential, respectively. A2R binding sites were also increased 21% in exposed neurons measured by radioligand [3H]rauwolscine binding assay. When treated with acute N2-hypoxia, the cell survival time (ST) was longer in exposed neurons, suggesting that a tolerance was induced. In addition, the ST for both groups of LC neurons was decreased by the A2R antagonist yohimbine and increased by the glutamate receptor antagonist kynurenic acid but not by MK-801; the decreased percentage of ST by yohimbine was larger and the increased percentage by kynurenic acid was smaller in exposed neurons. The results suggested that up-regulation of A2R and altered non-NMDA glutamate receptor function induced by chronic hypobaric hypoxia may underlie, in part, the decreased LC neuronal excitability and acute hypoxia tolerance.

Impact of anxiogenic stress on glucocorticoid sensitivity, glucose tolerance, and alloxan resistance in rats

Four episodes of immobilization stress caused anxiogenic behavioral disorders accompanied by a decrease in sensitivity to glucocorticoid hormones, by an increase in the activity of monoaminooxidase (MAO-B) in the brain tissue, an enhancement in glucose load tolerance, and a reduction in acute hypoxia tolerance in rats. Alloxan-induced diabetes was also associated with a reduction of rat behavioral activity in the open field along with an increase in the cerebral activity of MAO-B. Prior anxiogenic stress potentiated an alloxan-induced increase in cerebral MAO- B activity, enhanced concomitant behavioral disorders in rats, and increased the hyperglycemic effect of alloxan.

Acute exposure to graded levels of hypoxia in rainbow trout ( Salmo gairdneri): metabolic and respiratory adaptations

We have studied the mechanisms of acute hypoxia tolerance in rainbow trout ( Salmo gairdneri). Fish held at 9°C were exposed to various levels of hypoxia for 24 h. At an environmental P O 2 of 30 Torr, the fish showed an initial plasma acidosis probably of metabolic origin which was subsequently offset such that blood pH returned to normal within about 4h. Over this time period, red cell pH was maintained constant. Comparing the effects of different levels of hypoxia following 24 h exposure, oxygen consumption of the animal remained unchanged over a broad range of inspired oxygen tensions but declined by over 30% of normoxic values at inspired water P O 2 levels of 80 Torr. This appeared to be a true metabolic depression becaused signs of increased anaerobic metabolism did not occur until there was a further reduction in water oxygen levels. Rainbow trout appear to be able to maintain a relatively high energy status in their white muscle during 24 h exposure to severe hypoxia (water P O 2 = 30 Torr). As the level of hypoxia was intensified, there was a reduction in the oxygen gradient across the gills, probably facilitated in part by the release of catecholamines into the blood. The erythrocytic ATP:Hb 4 molar ratios declined with increasing hypoxic stress as did the pH gradient between the erythrocyte and plasma. The overall effect was no change in Hb O 2-affinity after 24 h exposure to severe hypoxia.

Role of hematocrit, heart mass, and high-altitude exposure in acute hypoxia tolerance.

Hypoxia tolerances in nitrogen dilution chamber of chickens at sea level and high altitudes, discussing role of hematocrit and heart mass