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Cardiovascular and autonomic nervous functions during acclimatization to hypoxia in conscious rats.

The time courses of changes in cardiovascular and autonomic nervous functions during acclimatization to hypoxia were studied in conscious Sprague-Dawley rats. The animals were kept under a 12:12-h light-dark cycle and exposed to hypoxia (1 atm, 10% O2). Implanted telemetry transmitters were used to record blood pressure (BP). Changes in heart rate (HR) and BP were monitored over a 21-day period, and variations before and during hypoxia were analyzed using the wavelet transform method. The HR, high-frequency power of HR variability (HR-HF) and low-frequency power of BP variability (BP-LF) were all significantly increased after 1 h of hypoxia, whereas the LF/HF ratio of HR variability did not change. After this initial increase, both HR and the BP-LF were found to decrease. On the first day of hypoxia, HR and BP-LF values were significantly lower than those of the control rats, whereas the HR-HF was higher. Subsequently, these values altered so that they were similar to the control after 14 days of hypoxia. In addition, the amplitude of diurnal variation in HR was reduced during hypoxia. These results suggest that a sequence of dynamic interactions between sympathetic and parasympathetic nervous activities might have important roles in the regulation of cardiovascular function during acclimatization to hypoxia.

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Impaired ventilatory acclimatization to hypoxia in mice lacking the immediate early gene fos B.

Earlier studies on cell culture models suggested that immediate early genes (IEGs) play an important role in cellular adaptations to hypoxia. Whether IEGs are also necessary for hypoxic adaptations in intact animals is not known. In the present study we examined the potential importance of fos B, an IEG in ventilatory acclimatization to hypoxia. Experiments were performed on wild type and mutant mice lacking the fos B gene. Ventilation was monitored by whole body plethysmography in awake animals. Baseline ventilation under normoxia, and ventilatory response to acute hypoxia and hypercapnia were comparable between wild type and mutant mice. Hypobaric hypoxia (0.4 atm; 3 days) resulted in a significant elevation of baseline ventilation in wild type but not in mutant mice. Wild type mice exposed to hypobaric hypoxia manifested an enhanced hypoxic ventilatory response compared to pre-hypobaric hypoxia. In contrast, hypobaric hypoxia had no effect on the hypoxic ventilatory response in mutant mice. Hypercapnic ventilatory responses, however, were unaffected by hypobaric hypoxia in both groups of mice. These results suggest that the fos B, an immediate early gene, plays an important role in ventilatory acclimatization to hypoxia in mice.

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Is the silvering process similar to the effects of pressure acclimatization on yellow eels?

To reproduce eels need to migrate over 6000 km and at pressure but before this migration they metamorphose into silver eels (silvering). The question raised in this study is to determine whether and how the silvering process contributes to pressure resistance. As migration represents a long swimming activity mainly performed with slow muscles, the red muscle energetics of pressure exposed silver eels was studied. By comparing these results to what has already been shown in yellow eels, we point out that the effects of the silvering process on pressure resistance are similar to the effects of pressure acclimatization in yellow eels. As previously shown, success of pressure acclimatization depends on membrane fluidity, but we raise the hypothesis that the high-pressure resistance of silver eels is due to more fluid membranes.

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Carotid sinus nerve responses and ventilatory acclimatization to hypoxia in adult rats following 2 weeks of postnatal hyperoxia.

Adult rats have decreased carotid body volume and reduced carotid sinus nerve, phrenic nerve, and ventilatory responses to acute hypoxic stimulation after exposure to postnatal hyperoxia (60% O2, PNH) during the first 4 weeks of life. Moreover, sustained hypoxic exposure (12%, 7 days) partially reverses functional impairment of the acute hypoxic phrenic nerve response in these rats. Similarly, 2 weeks of PNH results in the same phenomena as above except that ventilatory responses to acute hypoxia have not been measured in awake rats. Thus, we hypothesized that 2-week PNH-treated rats would also exhibit blunted chemoafferent responses to acute hypoxia, but would exhibit ventilatory acclimatization to sustained hypoxia. Rats were born into, and exposed to PNH for 2 weeks, followed by chronic room-air exposure. At 3-4 months of age, two studies were performed to assess: (1) carotid sinus nerve responses to asphyxia and sodium cyanide in anesthetized rats and (2) ventilatory and blood gas responses in awake rats before (d0), during (d1 and d7), and 1 day following (d8) sustained hypoxia. Carotid sinus nerve responses to i.v. NaCN and asphyxia (10 s) were significantly reduced in PNH-treated versus control rats; however, neither the acute hypoxic ventilatory response nor the time course or magnitude of ventilatory acclimatization differed between PNH and control rats despite similar levels of PaO2 . Although carotid body volume was reduced in PNH rats, carotid body volumes increased during sustained hypoxia in both PNH and control rats. We conclude that normal acute and chronic ventilatory responses are related to retained (though impaired) carotid body chemoafferent function combined with central neural mechanisms which may include brainstem hypoxia-sensitive neurons and/or brainstem integrative plasticity relating both central and peripheral inputs.

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Difference in brown adipose tissue effector response and associated thermoresponsiveness of ventromedial hypothalamic (VMH) neurons of 21 degrees C vs. 4 degrees C acclimatized rats to scrotal thermal stimulation.

The present study was designed (1) to determine if scrotal thermal stimulation would activate brown adipose tissue (BAT) thermogenesis, indicated by increases in interscapular BAT temperature (TIBAT) of cold acclimatized (CA, kept at 4 degrees C for 4 weeks) and room temperature acclimatized rats (RA, kept at 21 degrees C for 4 weeks) and (2) to compare the thermoresponsiveness of VMH neurons of both groups to scrotal heating and cooling. VMH extracellular activity was recorded in male RA and CA Sprague-Dawley rats when scrotal temperatures (Tsc) were changed between 5-40 degrees C via localized thermode (3 mm2) along with measurements of TscS and TIBATS. The CA-group showed significant increases in TIBATS during scrotal cooling compared to respective TIBATS of the RA-group. The ratio of VMH warm responsive (WRN), cold responsive (CRN) and temperature non-responsive (TNRN) neurons in the CA-group changed compared to that in the RA-group as a greater percentage of CRNs occurred in the CA-group. Also, the thermoresponsiveness of individual VMH CRNs of the CA rats was significantly increased compared to VMH CRNs of the RA-group. The results indicated that localized scrotal cooling of CA-rats (not RA-rats) can activate BAT thermogenesis. Furthermore, VMH CRNs increased their thermoresponsiveness with chronic cold exposure which may be an important neuronal adaptive response for the subsequent enhanced BAT thermogenic effector response seen in that group.

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Role of beta-adrenergic and cholinergic systems in acclimatization to hypoxia in the rat.

To role of beta-adrenergic and muscarinic cholinergic systems on maximal treadmill exercise performance and systemic O2 transport during hypoxic exercise (PIO2 approximately 70 Torr) was studied in rats acclimatized to hypobaric hypoxia (PIO2 approximately 70 Torr for 3 weeks, A rats) and in non-acclimatized littermates (NA rats). Untreated A rats had lower resting (fH) and maximal heart rate (fHmax) and cardiac output (Q), and higher maximal O2 uptake (VO2max) than NA. The only effect of cholinergic receptor blockade with atropine (Atp) was an increase in pre-exercise fH to comparable levels in A and in NA. beta 1-adrenergic receptor blockade with atenolol (Aten) lowered pre-exercise fH and (fHmax) to comparable values in A and in NA rats. However, since both pre-exercise fH and fHmax were lower in untreated A, the effect of Aten was relatively smaller in A. Aten reduced maximal exercise cardiac output (Qmax) in NA; however, tissue O2 extraction increased such that VO2max was not affected. Aten did not influence Qmax or any other parameter of systemic O2 transport in A. In conclusion the increased cholinergic tone may be responsible for the lower resting fH but not the lower fHmax of A; the integrity of the beta-adrenergic system is not necessary to attain VO2max in hypoxia either in A or in NA; the decreased response to beta-adrenergic stimulation in A limits the efficacy of this system on the mechanisms of systemic O2 transport and reduces the effect of its blockade on these mechanisms.

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Carotid body dopaminergic mechanisms are functional after acclimatization to hypoxia in goats.

Ventilatory acclimatization to sustained hypoxia (VASH) is the time-dependent increase in ventilation that occurs during prolonged exposure to hypoxia. We tested the hypothesis that carotid body (CB) dopaminergic mechanisms are down-regulated during VASH, which would allow CB afferent discharge and ventilation to increase beyond the initial response to hypoxia. Domperidone (DOM; 1.0 mg.kg-1) was administered intravenously to block CB dopamine (DA) receptors after VASH was complete in awake goats. DOM caused a significant augmentation of the ventilatory response to hypoxia in acclimatized goats, failing to support the hypothesis. We conclude that inhibitory CB dopaminergic function is not significantly reduced following prolonged hypoxia, and that down-regulation of CB dopaminergic mechanisms may not be involved in VASH in the goat.

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Skin type, minimal erythema dose (MED), and sunlight acclimatization.

Minimal erythema doses (MEDs) of individuals with different skin types were compared. Each skin type was shown to be statistically different from each other skin type in terms of sunburn sensitivity. Individuals of each skin type who primarily stayed indoors were compared with those who attempted to be outdoors. In the winter there was no difference between the sunburn sensitivity (MEDs) of these groups. During the summer, those who went outdoors were more resistant to sunburn than those who stayed indoors. In effect, acclimatization makes an individual respond to sunlight like a less sensitive skin type. However, acclimatization appears transitory, and benefits can be lost within a month or two.

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Changes of peroxisomal fatty acid metabolism during cold acclimatization in hibernating jerboa (Jaculus orientalis).

Jerboa (Jaculus orientalis) is a deep hibernator originating from sub-desert highlands and represents an excellent model to help to understand the incidence of seasonal variations of food intake and of body as well as environmental temperatures on lipid metabolism. In jerboa, hibernation processes are characterized by changes in the size of mitochondria, the number of peroxisomes in liver and in the expression of enzymes linked to fatty acid metabolism. In liver and kidney, cold acclimatization shows an opposite effect on the activities of the mitochondrial acyl-CoA dehydrogenase (-50%) and the peroxisomal acyl-CoA oxidase (AOX) (+50%), while in brown and white adipose tissues, both activities are decreased down to 85%. These enzymes activities are subject to a strong induction in brown and in white adipose tissue (3.4- to 7.5-fold, respectively) during the hibernation period which is characterized by a low body temperature (around 10 degrees C) and by starvation. Expression level of AOX mRNA and protein are increased during both pre-hibernation and hibernation periods. Unexpectedly, treatment with ciprofibrate, a hypolipemic agent, deeply affects lipolysis in brown adipose tissue by increasing acyl-CoA dehydrogenase activity (3.4-fold), both AOX activity and mRNA levels (2.8- and 3.8-fold, respectively) during pre-hibernation. Therefore, during pre-hibernation acclimatization, there is a negative regulation of fatty acid degradation allowing to accumulate a lipid stock which is later degraded during the hibernation period (starvation) due to a positive regulation of enzymes providing the required energy for animal survival.

Acclimatization↗

Altitude acclimatization, training and performance.

Exposure to altitude results in a reduction in partial pressure of oxygen in the arterial blood and a reduction in oxygen content. In an attempt to maintain aerobic metabolism during increased effort, a series of acclimatization responses occur. Among the most conspicuous of these responses is an increase in hemoglobin (Hb) concentration. The increase in Hb has been construed as the fundamental adaptation enabling increases in aerobic power and performance to occur on return to sea-level. However, the use of altitude to boost training adaptations and improve elite sea-level performance, although tantalizing, is largely unproven. The reasons appear to be many, ranging from the poor experimental designs employed, to the numerous strategies designed to manipulate the altitude experience and the large inter-individual differences in response patterns. However, other factors may also be important. Acclimatization has also been shown to induce alteration in selected properties of the muscle cell, some of which may be counterproductive. The processes involved in cation cycling, as an example, appear to be down-regulated. Changes in these processes could impair certain types of performance.

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NMR spectroscopic-based metabonomic studies of urinary metabolite variation in acclimatizing germ-free rats.

Understanding metabolic variation in "normal" animals is critical to the evaluation of drug-induced metabolic perturbation related to toxicity or pharmacology. NMR spectroscopic-based metabonomic methods were used to evaluate the acclimatization pathways of germ-free (axenic) rats to standard laboratory conditions concomitant with the associated development of gut microfloral communities. Urine samples from male Fischer 344 germ-free rats were collected over 21 days following introduction to a standard laboratory environment and analyzed using NMR spectroscopy. NMR spectra were data-reduced and analyzed using principal component analysis to visualize the changes in the host metabolic trajectory over the course of the study. At days 2 and 6 of the acclimatization process, there were marked episodes of glycosuria. In comparison to the concentrations in the 0-6 h samples, there was a reduction in the level of the tricarboxylic acid cycle intermediates (citrate, 2-oxoglutarate, and succinate) from 6 h to day 6, after which there was a sustained increase until the end of the study. The concentrations of hippurate and trimethylamine N-oxide increased over the course of the study in comparison to the levels at 0-6 h, with the most pronounced increase in the former between days 17 and 21. Phenylacetylglycine levels increased after 6 h whereas 3-hydroxypropionic acid was observed at day 12 and increased up to day 17. By day 21, the urinary metabolic profile was within the control range when compared to historical data, implying the establishment of a stable gut microflora. Although the metabolic alterations caused by the microbial alterations were not as substantial as those from metabolic dysfunction, their presence does have an effect on the interpretation of the profiles, the state of the animal, and the mechanism for the cause of such alterations. Furthermore, the use of oral drug delivery will have an effect on the microbial state, not only as a direct influence of the drug but also from it's associated vehicle. Such effects are likely to be observed particularly in the area of preclinical investigation where the data from these studies are of particular relevance.

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Ultrastructural changes of the carp (Cyprinus carpio) hepatocyte nucleolus during seasonal acclimatization.

BACKGROUND INFORMATION: The eurythermal fish carp (Cyprinus carpio) adjusts to the seasonal changes in the temperature and photoperiod of its habitat through diverse cellular and molecular mechanisms. We have observed that ribosomal biogenesis is modulated during the acclimatization process and correlates with profound phenotypic changes, reflecting a seasonal-dependent ultrastructural appearance of the nucleolar components. Previous studies using classical techniques showed that in winter-adapted carp the nucleolus appears to be segregated. In the present work, we have reassessed the nucleolar ultrastructural organization of the carp in summer- and winter-adapted fish by using more specific cytochemical and immunocytological techniques. RESULTS: The acetylation method provided evidence that the nucleolar organization is different between winter- and summer-adapted carp. In winter-adapted fish the fibrillar component appears as a unique mass surrounded by several granular caps, whereas in summer-adapted carp the fibrillar component forms few cordons surrounded by granular masses. The nucleolar structure and distribution of the condensed chromatin observed varies upon seasonal acclimatization. In winter the nucleolar chromatin is densely packed in masses that surround the nucleolus, whereas during summer it displays a rather looser organization formed by filaments that not only surround the nucleolus, but also go through the nucleolar body. Using the TdT (terminal deoxynucleotidyl transferase)-immunogold labelling technique, we detected condensed and decondensed nucleolar chromatin, and found some labelling of fibrillar components in both seasons. When liver tissue from summer-adapted carp was treated with AMD (actinomycin D), we observed that the rearrangement of the nucleolar components and condensed chromatin were similar to that found in winter-adapted fish, with differences in the distribution of the perinucleolar chromatin. CONCLUSIONS: The acetylation and TdT-immunogold labelling experiments indicated that the rearrangement of the nucleolar components of winter-adapted carp is very similar to the AMD-treated summer-adapted carp nucleolus, with the latter representing the repression of the ribosomal biogenesis that occurs during the cold season. Nevertheless, the distribution of the condensed perinucleolar chromatin in winter-adapted carp compared with AMD-treated cells suggests that the transcription of rRNA genes in winter-adapted fish is less strongly inhibited and does not lead to the classical segregation of the nucleolus of that described after AMD treatment. In addition, we have confirmed that carp hepatocyte nucleoli comprise only two main structural compartments: a fibrillar component and a granular component. Fibrillar centres were not observed.

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Angiotensin converting enzyme response to hypoxia in man: its role in altitude acclimatization.

The response of serum angiotensin converting enzyme (ACE) activity to three grades of hypoxia was studied in two groups of human subjects. Hypoxic gas mixtures having oxygen concentrations of 14, 12.6 and 10.4% were breathed successively for a period of 10 min at each concentration. Venous blood was sampled at the end of each of the three periods and arterial oxygen saturation was recorded throughout the experiment. The subjects were selected as being 'good' or 'poor' acclimatizers according to their history of acute mountain sickness. There were five subjects in each group. Hypoxia resulted in a reduction in ACE activity in both groups, the reduction being linear with respect to arterial oxygen saturation. The reduction in ACE activity was greater in the good acclimatizer group as shown by a significantly greater slope of the response line of ACE activity to arterial oxygen saturation. The significance of this finding in relation to the mechanism underlying acute mountain sickness is discussed.

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Effect of high altitude and exercise on microvascular parameters in acclimatized subjects.

The role of microvascular fluid shifts in the adaptation to hypobaric hypoxia and its contribution to the pathophysiology of AMS (acute mountain sickness) is unresolved. In a systematic prospective study, we investigated the effects of hypobaric hypoxia and physical exercise alone, and in combination, on microvascular fluid exchange and related factors. We used computer-assisted VCP (venous congestion plethysmography) on the calves of ten altitude-acclimatized volunteers. We investigated the effects of: (i) actively climbing to an altitude of 3196 m, (ii) airlifting these subjects to the same altitude, and (iii) exercise at low altitude. CFC (capillary filtration capacity), Pvi (isovolumetric venous pressure) and Qa (calf blood flow) were assessed before and after each procedure and then repeated after an overnight rest. Measurements of CFC showed no evidence of increased microvascular permeability after any of the procedures. Pvi was significantly decreased (P<0.001) from 20.3+/-4.4 to 8.9+/-4.3 mmHg after active ascent, and was still significantly lower (P=0.009) after overnight rest at high altitude (13.6+/-5.9 mmHg). No such changes were observed after the passive ascent (16.7+/-4.0 mmHg at baseline; 17.3+/-4.5 mmHg after passive ascent; and 19.9+/-5.3 mmHg after overnight rest) or after exercise at low altitude. After the active ascent, Qa was significantly increased. We also found a significant correlation between Qa, Pvi and the number of circulating white blood cells. In conclusion, we found evidence to support the hypothesis that increased microvascular permeability associated with AMS does not occur in acclimatized subjects. We also observed that the microvascular equilibrium pressure (Pvi) fell in inverse relation to the increase in Qa, especially in hypoxic exercise. We hypothesize that this inverse relationship reflects the haemodynamic changes at the microvascular interface, possibly attributable to the flow-induced increases in endothelial surface shear forces.

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Increased arterial pressure after acclimatization to 4300 m: possible role of norepinephrine.

Both systemic arterial pressure and sympathetic activity increase at high altitude, but neither the time course of these increases nor the relationship between them are known. Examination of resting and exercising data from our prior studies at sea level and on Pikes Peak indicated that blood epinephrine concentrations either showed little change (from sea level) or rose early in altitude exposure and then declined with acclimatization. By contrast, norepinephrine concentrations in blood and urine were not increased on arrival but consistently rose later in the acclimatization process. Also with altitude exposure, arterial pressure also increased concomitantly with the increase in norepinephrine concentrations. The study designs were not adequate to establish cause and effect, but the results were consistent with the concept that arterial pressure increments at altitude were associated with increased alpha adrenergic-mediated vascular tone.

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Seasonal acclimatization to extreme climatic conditions by black-capped chickadees (Poecile atricapilla) in interior Alaska (64 degrees N).

Winters in interior Alaska (64 degrees N) are characterized by short photoperiod (5L : 19D) and chronic subfreezing temperatures. To determine if seasonal acclimatization of black-capped chickadees (Poecile atricapilla) at high latitude differs from that of conspecifics at lower latitudes, standard metabolic rates (SMR), metabolic response to low temperature (-30 degrees C), nocturnal hypothermia, body mass, fat reserves, and conductance were measured over two winters and one summer in three groups of seasonally acclimatized birds. Body mass and conductance did not vary with season, although furcular fat levels were higher in winter. Birds used nocturnal hypothermia when exposed to -30 degrees C in summer or winter. Although SMR did not vary seasonally, winter SMRs differed between the two winters of the study. Nocturnal hypothermia in summer and decreased SMR in response to extreme conditions may either reflect plasticity inherent to all populations of black-capped chickadees or may result from individual variation within this northern population.

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Mitochondrial function in seasonal acclimatization versus latitudinal adaptation to cold in the lugworm Arenicola marina (L.).

Previous studies in marine ectotherms from a latitudinal cline have led to the hypothesis that eurythermal adaptation to low mean annual temperatures is energetically costly. To obtain more information on the trade-offs and with that the constraints of thermal adaptation, mitochondrial functions were studied in subpolar lugworms (Arenicola marina L.) adapted to summer cold at the White Sea and were compared with those in boreal specimens from the North Sea, either acclimatized to summer temperatures or to winter cold. During summer, a comparison of mitochondria from subpolar and boreal worms revealed higher succinate oxidation rates and reduced Arrhenius activation energies (Ea) in state 3 respiration at low temperatures, as well as higher proton leakage rates in subpolar lugworms. These differences reflect a higher aerobic capacity in subpolar worms, which is required to maintain motor activity at low but variable environmental temperatures--however, at the expense of an elevated metabolic rate. The lower activity of citrate synthase (CS) found in subpolar worms may indicate a shift in metabolic control within mitochondria. In contrast, acclimatization of boreal lugworms to winter conditions elicited elevated mitochondrial CS activities in parallel with enhanced mitochondrial respiration rates. With falling acclimation temperatures, the significant Arrhenius break temperature in state 3 respiration (11 degrees C) became insignificant (5 degrees C) or even disappeared (0 degrees C) at lower levels of Arrhenius activation energies in the cold, similar to a phenomenon known from hibernating vertebrates. The efficiency of aerobic energy production in winter mitochondria rose as proton leakage in relation to state 3 decreased with cold acclimation, indicated by higher respiratory control ratio values and increased adenosine diphosphate/oxygen (ADP/O) ratios. These transitions indicate reduced metabolic flexibility, possibly paralleled by a loss in aerobic scope and metabolic depression during winter cold. Accordingly, these patterns contrast those found in summer-active, cold-adapted eurytherms at high latitudes.

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Metabolic and ventilatory acclimatization to cold stress in house sparrows (Passer domesticus).

Passerines that overwinter in temperate climates undergo seasonal acclimatization that is characterized by metabolic adjustments that may include increased basal metabolic rate (BMR) and cold-induced summit metabolism (M(sum)) in winter relative to summer. Metabolic changes must be supported by equivalent changes in oxygen transport. While much is known about the morphology of the avian respiratory system, little is known about respiratory function under extreme cold stress. We examined seasonal variation in BMR, M(sum), and ventilation in seasonally acclimatized house sparrows from Wisconsin. BMR and M(sum) increased significantly in winter compared with summer. In winter, BMR increased 64%, and M(sum) increased 29% over summer values. The 64% increase in winter BMR is the highest recorded for birds. Metabolic expansibility (M(sum)/BMR) was 9.0 in summer and 6.9 in winter birds. The metabolic expansibility of 9.0 in summer is the highest yet recorded for birds. Ventilatory accommodation under helox cold stress was due to changes in breathing frequency (f), tidal volume, and oxygen extraction efficiency in both seasons. However, the only significant difference between summer and winter ventilation measures in helox cold stress was f. Mean f in helox cold stress for winter birds was 1.23 times summer values.

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