Influence of hypoxia and of hypoxemia on the development of cardiac activity in zebrafish larvae

Cardiac activity and anaerobic metabolism were analyzed in zebrafish larvae raised under normoxia (PO(2) = 20 kPa) and under chronic hypoxia (PO(2) = 10 kPa) at three different temperatures (25, 28, and 31 degrees C). Heart rate increased with development and with temperature. Under normoxia, cardiac output increased significantly at high temperature (31 degrees C), but not at 28 or at 25 degrees C. Under chronic hypoxia, however, heart rate as well as cardiac output increased at all temperatures in larvae at about hatching time or shortly thereafter. Cardiac activity of larvae raised for 2 wk after fertilization with a reduced hemoglobin oxygen-carrying capacity in their blood (hypoxemia; due to the presence of CO or of phenylhydrazine in the incubation water) was not different from control animals. Whole body lactate content of these animals did not increase. Thus there was no indication of a stimulated anaerobic energy metabolism. The increase in cardiac activity observed during hypoxia suggests that at about hatching time receptors are present that sense hypoxic conditions, and this information can be used to induce a stimulation of convective oxygen transport to compensate for a reduction in bulk oxygen diffusion in the face of a reduced oxygen gradient between environmental water and tissues. Under normoxia, however, the PO(2) gradient between environmental water and tissues and diffusional oxygen transport assure sufficient oxygen supply even if hemoglobin oxygen transport in the blood is severely impaired. Thus, under normoxic conditions and with a normal metabolic rate of the tissues, convective oxygen transport is not required until approximately 2 wk after fertilization.     

Hypoxia impairs the digestive advantage of individual southern catfish (Silurus meridionalis) with high resting metabolic rates and postprandial metabolic responses

Empirical studies suggest that individuals with a high resting metabolic rate (RMR) are at an advantage under favourable conditions because they digest food rapidly and exhibit a greater growth potential. However, we hypothesised that high-RMR individuals have less energy available for digestion under hypoxia than they do under normoxia due to their relatively high maintenance cost. To test this hypothesis, we measured the RMR and postprandial metabolic responses of juvenile southern catfish, Silurus meridionalis, under normoxia and moderate hypoxia. The results provided the first evidence that (1) both the RMR and postprandial metabolic rate showed repeatability across different water [O₂] conditions and (2) the correlation between the RMR and postprandial metabolic traits differs with changes in environmental factors (water [O₂]). These findings suggested that the digestive advantage of individual southern catfish with a high RMR is impaired under hypoxia.     

Hypoxia induces nitric oxide synthase in rheumatoid synoviocytes: consequences on NADPH oxidase regulation

We investigated the effects of hypoxia on inducible NO synthase (iNOS) activity and expression in rheumatoid arthritis (RA) synoviocytes. We further studied the relationship between nitrosative stress and NADPH oxidase (NOX) in such conditions. Human cultured synoviocytes were treated for 24 hours with IL-1β, TNF-α or neither, and submitted to hypoxia or normoxia for the last 6 hours. Nitrite production and iNOS expression were increased under hypoxia conditions in RA cells in comparison to normoxia. Hypoxia did not potentate the basal and cytokine-induced superoxide productions, while NOXs' subunit expression and p47-phox phosphorylation were increased. Nitrosylation of NOXs and p47-phox was not raised under hypoxia conditions. Finally, peroxynitrite production was significantly increased under hypoxia conditions, in comparison to normoxia. Our results provide evidence for upregulation of iNOS and NOX activities in RA synoviocytes under hypoxia conditions, associated to an increased peroxynitrite production. Synovial cell metabolism under hypoxia conditions might be different from that in normoxia.     

The influence of haemoglobin on behavioural thermoregulation and oxygen consumption in Daphnia carinata

When placed in a temperature gradient, most ectotherms have a strict thermal preference that is lowered on exposure to hypoxia. Branchiopods, small aquatic crustaceans, are known to synthesise haemoglobin (Hb) when exposed to hypoxia; hypoxia can occur diurnally and seasonally in ponds. The effect of Hb on behavioural thermoregulation in the branchiopod Daphnia carinata following exposure to both normoxia and hypoxia was examined. Control animals raised in normoxia (Po2=150 mmHg, [Hb]=0.026+/-0.007 mg g dry wt-1) and Hb-rich animals raised in hypoxia (Po2=70 mmHg, [Hb]=0.080+/-0.017 mg g dry wt-1) were placed (N=30) in a tube (length=500 mm, diameter=8 mm) filled with pond water. In the absence of a thermal gradient, control and Hb-rich animals in normoxic water were uniformly distributed along the tube. The presence of a thermal gradient (13 degrees -28 degrees C) elicited clustering at a preferred temperature, T approximately 23 degrees C for both groups. Exposure to hypoxic water in a thermal gradient resulted in a behavioural shift: T approximately 16 degrees C for controls and T approximately 19 degrees C for Hb-rich animals. Measurements of oxygen consumption (V&d2;o2) at fixed temperatures revealed that Hb is associated with a metabolic acclimation to hypoxia.     

Hypoxia induces nitric oxide synthase in rheumatoid synoviocytes: consequences on NADPH oxidase regulation

Abstract

We investigated the effects of hypoxia on inducible NO synthase (iNOS) activity and expression in rheumatoid arthritis (RA) synoviocytes. We further studied the relationship between nitrosative stress and NADPH oxidase (NOX) in such conditions. Human cultured synoviocytes were treated for 24 hours with IL-1β, TNF-α or neither, and submitted to hypoxia or normoxia for the last 6 hours. Nitrite production and iNOS expression were increased under hypoxia conditions in RA cells in comparison to normoxia. Hypoxia did not potentate the basal and cytokine-induced superoxide productions, while NOXs’ subunit expression and p47-phox phosphorylation were increased. Nitrosylation of NOXs and p47-phox was not raised under hypoxia conditions. Finally, peroxynitrite production was significantly increased under hypoxia conditions, in comparison to normoxia. Our results provide evidence for upregulation of iNOS and NOX activities in RA synoviocytes under hypoxia conditions, associated to an increased peroxynitrite production. Synovial cell metabolism under hypoxia conditions might be different from that in normoxia.     

Effects of acute hypoxia and CO2 inhalation on systemic and peripheral oxygen uptake and circulatory responses during moderate exercise

The effect of acute hypoxia and CO2 inhalation on leg blood flow (LBF), on leg vascular resistance (LVR) and on oxygen supply to and oxygen consumption in the exercising leg was studied in nine healthy male subjects during moderate one-leg exercise. Each subject exercised for 20 min on a cycle ergometer in four different conditions: normoxia, normoxia + 2% CO2, hypoxia corresponding to an altitude of 4000 m above sea level, and hypoxia + 1.2% CO2. Gas exchange, heart rate (HR), arterial blood pressure, and LBF were measured, and arterial and venous blood samples were analysed for PCO2, PO2, oxygen saturation, haematocrit and haemoglobin concentration. Systemic oxygen consumption was 1.83 l.min-1 (1.48-2.59) and was not affected by hypoxia or CO2 inhalation in hypoxia. HR was unaffected by CO2, but increased from 136 beat.min-1 (111-141) in normoxia to 155 (139-169) in hypoxia. LBF was 6.5 l.min-1 (5.4-7.6) in normoxia and increased significantly in hypoxia to 8.4 (5.9-10.1). LVR decreased significantly from 2.23 kPa.l-1.min (1.89-2.99) in normoxia to 1.89 (1.53-2.52) in hypoxia. The increase in LBF from normoxia to hypoxia correlated significantly with the decrease in LVR. When CO2 was added in hypoxia a significant correlation was also found between the decrease in LBF and the increase in LVR. In normoxia, the addition of CO2 caused a significant increase in mean blood pressure. Oxygen consumption in the exercising leg (leg VO2) in normoxia was 0.97 l.min-1 (0.72-1.10), and was unaffected by hypoxia and CO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impacts of oxygen deficiency on embryo life-history traits of migratory locust Locusta migratoria from low and high altitudes

Hypoxia challenges aerobic organisms in numerous environments, and hypoxic conditions may become more severe under future climate-change scenarios. The impact of hypoxia on the development of terrestrial insect embryos is not well understood. Here, to address this gap, embryonic life-history traits of migratory locust Locusta migratoria from low-altitude and high-altitude regions were compared under 2 oxygen levels: normoxia (i.e., 21 kPa oxygen partial pressure and mild hypoxia (i.e., 10 kPa oxygen partial pressure). Our results demonstrated that, whether reared under normoxia or mild hypoxia, L. migratoria from high-altitude populations had longer developmental times, reduced weight, and lower mean relative growth rate as compared with those from low-altitude populations. When transferred from normoxia to mild hypoxia, nearly all the tested life-history traits presented significant negative changes in the low-altitude populations, but not in the high-altitude populations. The factor ‘strain’ alone explained 18.26%–54.59% of the total variation for traits, suggesting that the phenotypic differences between L. migratoria populations from the 2 altitudes could be driven by genetic variation. Significant genetic correlations were found between life-history traits, and most of these showed differentiation between the 2 altitudinal gradients. G-matrix comparisons showed significant structural differences between L. migratoria from the 2 regions, as well as several negative covariances (i.e., trade-offs) between traits in the low-altitude populations. Overall, our study provides clear evidence that evolutionary divergence of embryonic traits between L. migratoria populations from different altitudes has occurred.     

Polymerized bovine hemoglobin decreases oxygen delivery during normoxia and acute hypoxia in the rat

Hemoglobin-based oxygen carriers (HBOC) have been primarily studied for blood loss treatment. More recently infusions of HBOC in euvolemic subjects have been proposed for a wide variety of potential therapies in which increased tissue oxygenation would be beneficial. However, compared with the exchange transfusion models to study blood loss, less is known about HBOC oxygen delivery and vasoacitvity when it is infused in euvolemic subjects. We hypothesized that HBOC [polymerized bovine hemoglobin (PBvHb)] infusion creating hypervolemia would increase oxygen delivery to tissues during acute global hypoxia. Vascular oxygen content and hemodynamics were determined after euvolemic rats were infused with 3 ml of either lactated Ringer or PBvHb solution (13 g/dl, 1.3 g/kg) during acute hypoxia (FIO2 = 10%, 4 h) or normoxia (FIO2 = 21%) exposure. Our data demonstrated that compared with Ringer-infused animals, in hypoxia and normoxia, PBvHb treatment improved oxygen content but raised mean arterial pressure, lowered stroke volume, heart rate, and cardiac index, which resulted in a net reduction in blood flow and oxygen delivery to the tissues. The PBvHb vasoactive effect was similar in magnitude and direction as to the Ringer-infused animals treated with a nitric oxide synthase inhibitor nitro-l-arginine, suggesting the PBvHb effect is mediated via nitric oxide scavenging. We conclude that infusion of PBvHb is not likely to be useful in treating global hypoxia under these conditions.     

Metabolic and physiological responses in tissues of the long-lived bivalve Arctica islandica to oxygen deficiency

In Arctica islandica, a long lifespan is associated with low metabolic activity, and with a pronounced tolerance to low environmental oxygen. In order to study metabolic and physiological responses to low oxygen conditions vs. no oxygen in mantle, gill, adductor muscle and hemocytes of the ocean quahog, specimens from the German Bight were maintained for 3.5 days under normoxia (21 kPa=controls), hypoxia (2 kPa) or anoxia (0 kPa). Tissue levels of anaerobic metabolites octopine, lactate and succinate as well as specific activities of octopine dehydrogenase (ODH) and lactate dehydrogenase (LDH) were unaffected by hypoxic incubation, suggesting that the metabolism of A. islandica remains fully aerobic down to environmental oxygen levels of 2 kPa. PO(2)-dependent respiration rates of isolated gills indicated the onset of metabolic rate depression (MRD) below 5 kPa in A. islandica, while anaerobiosis was switched on in bivalve tissues only at anoxia. Tissue-specific levels of glutathione (GSH), a scavenger of reactive oxygen species (ROS), indicate no anticipatory antioxidant response takes place under experimental hypoxia and anoxia exposure. Highest specific ODH activity and a mean ODH/LDH ratio of 95 in the adductor muscle contrasted with maximal specific LDH activity and a mean ODH/LDH ratio of 0.3 in hemocytes. These differences in anaerobic enzyme activity patterns indicate that LDH and ODH play specific roles in different tissues of A. islandica which are likely to economize metabolism during anoxia and reoxygenation.     

Models of parent-offspring conflict. IV. Suppression: Evolutionary retaliation by the parent

We have earlier analysed ESSs for the amount of parental investment (PI) that offspring are expected to solicit from their parents, given that parents acquiesce to offspring demands. The present paper considers evolutionary retaliation by the parent for species where only one parent provides PI. Two genetic loci are envisaged: one (the ‘conflictor’ locus) determines the extent of offspring solicitation; the other (the ‘suppressor’ locus) determines how parents retaliate. Solicitation is assumed to carry a cost which may affect a particular offspring uniquely if time and energy are the major costs, or may affect all offspring in a brood equally if the main cost is predation risk. Two kinds of parental retaliation are possible. Parents may supply PI in proportion to offspring demands, or may ignore solicitation altogether and give a fixed PI. Analytical models of conflict in which the parent supplies PI in proportion to solicitation yield pure ESSs with PI at a compromise level between parent and offspring interests. These are termed ‘pro rata’ ESSs. Where solicitation costs are high, an ‘offspring wins’ ESS (offspring get all they ‘want’) is possible especially for forms of conflict that affect future sibs, and a ‘parent wins’ ESS (parent supplies its optimum) is possible especially for conflict that affects contemporary sibs. When parental retaliation takes the form of ignoring offspring solicitation, this can lead to a ‘parent wins’ ESS if costs of ignoring solicitation are negligible, but where parental insensitivity carries costs, the result is an unresolvable evolutionary chase with cycling frequencies of alleles coding for parent and offspring strategies. ‘Pro rata’ ESSs cannot be invaded by ‘ignore solicitation’ mutants but ‘pro rata’ mutants can often invade at certain stages in ‘ignore solicitation’ limit cycles. We therefore conclude that the probable evolutionary end product for most species will be the ‘pro rata’ ESS in which the parent supplies more PI than would be optimal in the absence of conflict, but less PI than would be an ESS for the offspring in the absence of parental retaliation. Such ESSs will be characterized by solicitation costs; offspring will ‘ask’ for more PI than they get. In nature, under similar conditions, highest conflict will occur when both parents sustain equally the effects of conflict, or when conflict affects contemporary rather than future sibs.     

Effect of antihypoxic agents on the cyclic nucleotide content in different brain structures in normo-oxia and hypoxia

A study was made of the effects of isothiobarbamine and guthimine (10 and 50 mg/kg, respectively) on the content of cAMP and cGMP in the brain cortex (BC) and hippocamp under normal conditions and hypoxia. Isothiobarbamine did not change the content of both cyclic nucleotides under normoxia, whereas under hypoxia it reduced the level of the cyclic nucleotides in the BC and raised it in the hippocamp. Guthimine increased their content in the BC and did not change it in the hippocamp under normoxia, whereas under hypoxia it increased the cAMP content in the hippocamp and did not change it in the BC. The cGMP content descended in both the structures under study.     

Oxygen consumption in offspring tawny owls Strix aluco is associated with colour morph of foster mother

In several colour polymorphic species, morphs differ in thermoregulation either because dark and pale surfaces absorb solar radiation to a different extent and/or because morphs differ in key metabolic processes. Morph-specific thermoregulation may potentially account for the observation that differently coloured individuals are frequently not randomly distributed among habitats, and differ in many respects, including behaviour, morphology, survival and reproductive success. In a wild population of the colour polymorphic tawny owl Strix aluco, a recent cross-fostering experiment showed that offspring raised and born from red mothers were heavier than those from grey mothers. In the present study, we tested in the same individuals whether these morph-specific offspring growth patterns were associated with a difference in metabolic rate between offspring of red and grey mothers. For this purpose, we measured nestling oxygen consumption under two different temperatures (laboratory measurements: 4 and 20°C), and examined the relationships between these data sets and the colour morph of foster and biological mothers. After controlling for nestling body mass, oxygen consumption at 20°C was greater in foster offspring raised by grey foster mothers. No relationship was found between nestling oxygen consumption and coloration of their biological mother. Therefore, our study indicates that in our experiment offspring raised by grey foster mothers showed not only a lower body mass than offspring raised by red foster mothers, but also consumed more oxygen under warm temperature. This further indicates that rearing conditions in nests of grey mothers were more stressful than in nests of red mothers.     

Chronic hypoxia augments uterine artery distensibility and alters the circumferential wall stress-strain relationship during pregnancy.

Pregnancy-associated increases in uterine artery (UA) blood flow are due, in part, to vasoactive and growth-related changes that enlarge UA diameter. Although active and passive mechanical factors can contribute to this enlargement, their role is less well understood. We hypothesized that pregnancy increased UA distensibility and/or decreased myogenic tone. Given the fetal growth restriction and lower UA flow seen under chronic hypoxia, we further hypothesized that chronic hypoxia opposed these normal active and passive mechanical changes. UA were isolated from 12 nonpregnant and 12 pregnant (0.7 gestation) guinea pigs housed under normoxia or chronic hypoxia (3,960 m) and studied by pressure myography. Pregnancy increased UA diameter similarly under normoxia and hypoxia. Although chronic hypoxia raised resting tone in UA from nonpregnant guinea pigs to approximately 20% and tone was greater in preconstricted pregnant chronically hypoxic vs. normoxic UA (both P<0.01), there was an absence of myogenic response (i.e., an increase in tone with rising pressure) in all groups. Pregnancy increased UA distensibility 1.5-fold but did not change stiffness or the stress-strain relationship. Compared with vessels from normoxic pregnant animals, hypoxic pregnancy raised UA distensibility fourfold, decreased stiffness (rate constant b=3.80+/-1.06 vs. 8.92+/-1.25, respectively, P<0.01), lowered elastin by 50%, and shifted the stress-strain relationship upward such that four times as much strain was present at a given stress. We concluded that increased distensibility and low myogenic tone contribute to enlarging UA diameter and raising UA blood flow during pregnancy. Chronic hypoxia exaggerates the rise in distensibility and alters the stress-strain relationship in ways that may provoke vascular injury.     

Hypoxia reduced upper thermal limits causing cellular and nuclear abnormalities of erythrocytes in Nile tilapia,Oreochromis niloticus

Global warming is a threat across the world that leads to estimates of the upper thermal limits of ectothermic species. Increased water temperature up-regulates oxygen consumption and metabolic rates, and alters the physiological processes. In this study, we identified the critical thermal maxima (CTmax) and physiological responses under normoxia and hypoxia in Nile tilapia, Oreochromis niloticus. CTmax was 41.25 °C under hypoxia and 44.50 °C under normoxia. Compared to normoxia, lower values of hemoglobin (Hb) and red blood cells (RBCs) were observed at the CTmax under hypoxia. In contrast, higher values of white blood cells (WBCs) and blood glucose (Glu) levels were observed at the CTmax under hypoxia. Consequently, higher frequencies of micronucleus, cellular and nuclear abnormalities of erythrocytes were observed at the CTmax under hypoxia. These results suggest that high temperature tolerance and subsequent physiology are significantly affected by the oxygen supply in Nile tilapia. As climate vulnerability is intensifying day by day, this data will be helpful in successful management practice for the aquatic environment having low oxygen content.     

Nitric oxide mediates metabolism as well as respiratory and cardiac responses to hypoxia in the snail lymnaea stagnalis

Lymnaea stagnalis were exposed to hypoxic and chemical challenges while ventilation, heart rate and metabolism were monitored. Hypoxia increased ventilatory behavior, but this response was eliminated by immersion in 0.75 mM nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7 NI). 7 NI also suppressed ventilatory behavior under normoxia. 10.0 mM L-arginine (ARG, the NOS substrate) increased ventilatory behavior under normoxia, but dampened the hypoxic response. The heart-rate response to NOS inhibition exhibited dose-dependent contradictory characteristics. Under both normoxia and hypoxia 0.25 mM 7 NI increased heart rate, while 0.75 mM 7 NI suppressed it. The effect of 0.50 mM 7 NI depended on whether normoxia or hypoxia was coincident; under normoxia 0.50 mM 7 NI increased heart rate, while under hypoxia this concentration suppressed heart rate. Exposure to ARG did not elicit dose-dependent contradictory responses. Heart rate increased when treated with 10.0 mM ARG under normoxia and hypoxia, while 1.0 mM ARG increased heart rate only under hypoxia. Metabolic responses to NOS inhibition also exhibited dose-dependent contradictory changes. V.O2 decreased over 60% in response to 0.75 mM 7 NI, and baseline V.O2 was restored when exposure ceased. In contrast, 0.25 mM 7 NI increased V.O2 10%, and the increase continued after exposure ceased. 0.50 mM 7 NI decreased V.O2 40%, but V.O2 increased when exposure ceased. ARG had only the effect of increasing V.O2, and only at 10.0 mM concentration. Based on these results and on NO's known role as a neuromodulator, we conclude that the cardio-respiratory responses to hypoxia are, in part, mediated by NO.     

Influence of temperature and ambient oxygen on the swimming energetics of cyprinid larvae and juveniles

Synopsis The relationship between respiration and swimming speed of larvae and juveniles (2–100 mg fresh mass) of Danube bleak, Chalcalburnus chalcoides (Cyprinidae), was measured at 15° and 20° C under hypoxic (50% air saturation), normoxic, and hyperoxic (140% air saturation) conditions. In a flow-tunnel equipped with a flow-through respirometer the animals swam at speeds of up to 8 lengths · s^-1; speeds were sustained for at least two minutes. The mass specific standard, routine, and active respiration rates declined with increasing body mass at both temperatures. Metabolic intensity increased with temperature, but also the critical swimming speed (at which oxygen uptake reached its maximum) was higher at 20° than at 15° C by about 30%. Nevertheless, the oxygen debt incurred by the fish at the highest speeds was about 40%, and the net cost of swimming about 32%, lower at 20° than at 15°C. The standard metabolic rate was more strongly dependent on temperature (Q₁₀ around 2.5) than the maximum active rate (Q₁₀ below 2). Whereas standard and routine respiration rates were well regulated over the pO₂-range investigated (8.5–25.8 kPa), the active rates showed a conformer-like pattern, resulting in factorial scopes for activity between 2 and 4. Under hypoxia, the critical swimming speed was lower than under normoxia by about 1.51 · s^-1, but the net cost of swimming was also lower by about 30%. On the other hand, hyperoxia neither increased the swimming performance nor did it lead to a further increase of the metabolic cost of swimming. The hypoxia experiments suggest that in response to lowered tensions of ambient oxygen maintenance functions of metabolism not directly related to swimming may be temporarily reduced, leading to increased apparent swimming efficiency under these conditions. The responses of the larvae of Danube bleak to low temperature and low ambient oxygen are discussed in terms of the metabolic strategies by which energy-limited animals meet the challenge of environmental deterioration.     

Acute in vitro hypoxia and high-altitude (4,559 m) exposure decreases leukocyte oxygen consumption

Hypoxia impairs metabolic functions by decreasing activity and expression of ATP-consuming processes. To separate hypoxia from systemic effects, we tested whether hypoxia at high altitude affects basal and PMA-stimulated leukocyte metabolism and how this compares to acute (15 min) and 24 h of in vitro hypoxia. Leukocytes were prepared at low altitude and ～24 h after arrival at 4559 m. Mitochondrial oxygen consumption (JO?) was measured by respirometry, oxygen radicals by electron spin resonance spectroscopy, both at a Po? = 100 mmHg (JO?,???) and 20 mmHg (JO?,??). Acute hypoxia of leukocytes decreased JO? at low altitude. Exposure to high altitude decreased JO?,???, whereas JO?,?? was not affected. Acute hypoxia of low-altitude samples decreased the activity of complexes I, II, and III. At high altitude, activity of complexes I and III were decreased when measured in normoxia. Stimulation of leukocytes with PMA increased JO?,??? at low (twofold) and high altitude (five-fold). At both locations, PMA-stimulated JO? was decreased by acute hypoxia. Basal and PMA-stimulated reactive oxygen species (ROS) production were unchanged at high altitude. Separate in vitro experiments performed at low altitude show that ～75% of PMA-induced increase in JO? was due to increased extra-mitochondrial JO? (JO?(,res); in the presence of rotenone and antimycin A). JO?(,res) was doubled by PMA. Acute hypoxia decreased basal JO?(,res) by ～70% and PMA-stimulated JO?(,res) by about 50% in cells cultured in normoxia and hypoxia (1.5% O?; 24 h). Conversely, 24 h in vitro hypoxia decreased mitochondrial JO?,??? and JO?,??, extra-mitochondrial, basal, and PMA-stimulated JO? were not affected. These results show that 24 h of high altitude but not 24 h in vitro hypoxia decreased basal leukocyte metabolism, whereas PMA-induced JO? and ROS formation were not affected, indicating that prolonged high-altitude hypoxia impairs mitochondrial metabolism but does not impair respiratory burst. In contrast, acute hypoxia impairs respiratory burst at either altitude.     

Effects of hypoxia on metabolic rate of conscious adult cats during cold exposure

Oxygen consumption (VO2) and shivering movements were recorded in adult, conscious cats in a thermoneutral (24-27 degrees C) and in a cold (3-8 degrees C) environment during normoxia, hypoxia, or hyperoxia for 55 min. In the cold environment, VO2 correlated with shivering index (SI) under conditions of normoxia or ambient hypoxia (FIO2 = 0.12). During normoxia, VO2 was 63% higher in the cold than the thermoneutral environment. Ambient hypoxia acutely reduced VO2 in cold and thermoneutral environments, the decrement being greater for the former than the latter. Similarly, the variation in VO2 for unit change in SI was greater in hypoxia than normoxic conditions, suggesting that hypoxia influenced nonshivering as well as shivering components of cold-induced VO2. Hypoxia induced by CO (FICO = 0.002) also reduced VO2 and SI, a result that is consistent with previous results indicating that carotid body chemoreceptors do not mediate the suppression of shivering by ambient hypoxia. Hyperoxia increased VO2 and SI in the cold, and the effects of both hypoxia and hyperoxia in the cold were antagonized by increasing FICO2 to 0.03. The results demonstrate that hypoxia suppresses VO2 in the cold by reducing the intensity of shivering and, probably, by an action on metabolic rate that is unrelated to cold-induced calorigenesis.     

Ventilatory and metabolic responses to cold and hypoxia in intact and carotid body-denervated rats.

The effects of hypoxia on thermoregulation and ventilatory control were studied in conscious rats before and after carotid denervation (CD). Measurements of metabolic rate (VO2), ventilation (V), shivering intensity (SI), and colonic temperature (Tc) were made in groups of eight rats subjected to three protocols. In protocols 1 and 2, at ambient temperature (Ta) of 25 and 5 degrees C, respectively, rats were exposed to normoxia and hypoxia [inspired O2 fraction (FIO2) 0.13-0.11]. In protocol 3, Ta was decreased from 25 to 5 degrees C in 30-min steps of 5 degrees C. Recordings were made in normoxia and hypoxia (FIO2 0.12). The results show that in both intact and CD rats 1) in normoxia, cold exposure increased VO2, V, and SI, and these increases were proportional to the decrease in Ta; 2) hypoxia induced only a transient decrease in SI, and, for a given Ta, VO2 was reduced whereas V and SI were increased; and 3) in CD rats, V increased less during cold exposure in both normoxia and hypoxia; VO2 and Tc were more depressed during hypoxia. It is concluded that 1) the interaction between Ta and FIO2 in the control of V is partly dependent on the carotid body afferents, 2) shivering thermogenesis may be transiently affected by hypoxia independently of the carotid body afferents, and 3) nonshivering thermogenesis may be directly inhibited by hypoxia, especially during cold exposure.