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Dynamics of changes in activity and protein expression of antiradical (MnSOD), glutathione-dependent (glutathione peroxidase, glutathione reductase) and NADP⁺-generated (isocitrate dehydrogenase) enzymes as well as in the energy metabolism indeces in rat liver mitochondria under hypoxia- reoxygenation of different duration (1, 3, 7 14 days) were studied. Prolonged hypoxia-reoxygenation was characterized by phase changes of the corticosterone concentration in rat blood, which corresponded to the changes in energy metabolism as well as in pro- and antioxidant balance in rat liver mitochondria. It has been shown that short-term (1 day) hypoxia-reoxygenation (5% O2 in the gas mixture) led to an increase in the blood corticosterone concentration and a significant activation of oxidative processes and energy metabolism in rat liver mitochondria, the intensity of which was reduced to 3rd day. Long- term hypoxia--reoxygenation (7-14th days) led to the gradual depletion of the organism adaptive capabilities, as evidenced by a significant decline in the blood corticosterone concentration, an increase in the content of secondary products of lipid peroxidation, an imbalance in pro- and antioxidant reactions and reduction of energy capacity in liver cells mitochondria. It has been shown that the glutathione peroxidase protein expression and enzymatic activity increased constantly during the whole experimental period and correlated positively with the level of H₂O₂. The amount of Mn-SOD protein as well as it's enzymatic activity was lower in the first seven days of experiment, and it was increased in consequent days up to the control level on 14thday. Increased activity of glutathione peroxidase, glutathione reductase and NADP+⁺dependent isocitrate dehydrogenase during prolonged hypoxia - eoxygenation indicates that glutathione- and NADPH-generating enzymes, were actively involved in the antioxidant protect.

The effect of a metabolic precursor of natural activator of mitochondrial ATP-dependent potassium channel (mitochondrial K+(ATP))--uridine on animal's endurance to physical stress was studied. The endurance was determined by recording the time period during which the rat loaded with a plummet of 20% of body weight can swim until physical exhaustion at 32 degrees C. It was found that highly resistant animals swam until exhaustion for 7.40 ± 0.35 min, whereas low resistant rats hold out 2.07 ± 0.10 min only. The injection of uridine influenced the swimming time of the animals, increasing it twofold in low-resistant rats. The effect of uridine was decreased by injection of inhibitors of mitochondrial K+(ATP) channel. It was found that the injection of uridine into low resistant rats increased the rate of potassium transport in mitochondria isolated from liver of these rats, and inhibitors of the channel prevent the channel activating effect of uridine. The role of mitochondrial K+(ATP) cannel in the formation of animal's resistance to physical stress and protection of tissues from hypoxia is discussed.

The effect of mitochondrial ATP-dependent K(+)-channel (K(+)ATP-channel) opener diazoxide (DZ) on transmembrane potassium exchange and reactive oxygen species (ROS) formation under the opening of mitochondrial permeability transition pore (MPTP) was studied in rat liver mitochondria. The activation of K(+)-cycling (K(+)-uptake and K(+)/H(+)-exchange) by DZ was established with peak effect at < or = 500 nM. It was shown that MPTP opening as well resulted in the activation of K(+)-cycling together with simultaneous activation of Ca(2+)-cycle in mitochondria. In the absence of depolarization Ca(2+)-cycle is supported by MPTP and Ca(2+)-uniporter. The stimulation of K(+)/H(+)-exchange by MPTP opening led to the activation of K(+)-cycle, but further activation of K(+)/H(+)-exchange resulted in MPTP inhibition. Under the same conditions the decrease in mitochondrial ROS production was observed. It was proposed that the decrease in ROS formation together with K(+)/H(+)-exchange activation could be the constituents of the complex effect of MPTP inhibition induced by K(+)ATP-channel opener.

In stress, it was showed the organ and tissue changes associated with damage by lipid peroxides, and the disrupted barrier function. As a consequence, it was to lead to a syndrome of "stress-induced lung" and violation of oxygen delivery to the tissues and hypoxia. Purpose of the study was to investigate the dynamics of changes in gas exchange, blood glucose, body temperature, oxidant and antioxidant system activity, as well as mitochondrial respiration by Chance under the influence of chronic stress (6-hour immobilization daily for 3 weeks). It was identified 4 phase changes of energy metabolism in the dynamics of chronic stress. In the first phase, hypomethabolic, instability oxidative metabolism, decreased oxidation of NAD-dependent substrates, significant elevation of FAD-dependent substrates oxidation and low MRU were found. The activity of superoxide dismutase (MnSOD) was increased; it was occurred on a background low activity of glutathione peroxidase, and of misbalanced antioxidant system. After seven immobilizations, second phase-shift in energy metabolism, was observed, and then the third phase (hypermetabolic) started. It was characterized by gradual increase in oxidative metabolism, the restoration of oxidation of NAD-dependent substrates, MRU, as well as optimizing balance of oxidant and antioxidant systems. The fourth phase was started after 15 immobilizations, and characterized by the development of adaptive reactions expressed in increased tolerance of energy metabolism to the impact of immobilization. The results are correlated with changes in the dynamics of blood corticosterone. Thus, it was found the phase character of the energy metabolism rebuilding during the chronic stress.

The effect of potassium on state 4 respiration (substrate oxidation in the absence of ADP) was investigated. It was shown that potential-dependent potassium uptake in the brain mitochondria results in mitochondrial depolarization. Taking into account depolarization effect of potassium, the contribution of the endogenous proton leak as well as K(+)-uptake to the respiration rate was calculated. It was shown that such estimation allows the share of ATP-dependent potassium channel contribution to potential-dependent potassium uptake to be determined by polarographic method.

The effect of potential-dependent potassium uptake on reactive oxygen species (ROS) generation in mitochondria of rat brain was studied. It was found that the effect of K+ uptake on ROS production in the brain mitochondria under steady-state conditions (state 4) was determined by potassium-dependent changes in the membrane potential of the mitochondria (ΔΨm). At K+ concentrations within the range of 0-120 mM, an increase in the initial rate of K(+)-uptake into the matrix resulted in a decrease in the steady-state rate of ROS generation due to the K(+)-induced depolarization of the mitochondrial membrane. The selective blockage of the ATP-dependent potassium channel (K(ATP)(+)-channel) by glibenclamide and 5-hydroxydecanoate resulted in an increase in ROS production due to the membrane repolarization caused by partial inhibition of the potential-dependent K+ uptake. The ATP-dependent transport of K+ was shown to be ~40% of the potential-dependent K+ uptake in the brain mitochondria. Based on the findings of the experiments, the potential-dependent transport of K+ was concluded to be a physiologically important regulator of ROS generation in the brain mitochondria and that the functional activity of the native K(ATP)(+)-channel in these organelles under physiological conditions can be an effective tool for preventing ROS overproduction in brain neurons.

The effect of Ca(2+)-induced opening of cyclosporine-sensitive pore (mitochondrial permeability transition pore, MPTP) on the oxygen consumption and mitochondrial functional state was studied in the rat liver mitochondria. It was shown that, with the use of glutamate as oxidation substrate, in the absence of depolarization MPTP opening results in the increase of steady state respiration rate because of the activation of cyclosporine-sensitive Ca2+/H(+)-exchange and Ca2+ cycling, which was supported by the simultaneous work of MPTP and Ca(2+)-uniporter. With the aid of selective blockers, cyclosporine A and ruthenium red, it was shown that MPTP and Ca(2+)-uniporter contribute equally to the Ca(2+)-cycling and mitochondrial respiration. It was shown that bioenergetic effects of MPTP opening under steady state conditions (increase in the oxygen consumption rate under substrate oxidation without ADP, decrease in respiratory control ratio as well as the effectiveness of ATP synthesis, P/O) are close to the functional alterations, which result from the increase of endogenous proton conductance of mitochondrial membrane. Uncoupling effect of MPTP opening, by itself, had no effect on phosphorylation rate, which remains relatively stable because the fall of P/O is compensated by the activation of respiratory chain and the increase in the rate of state 3 respiration. It was concluded that under physiologically normal conditions MPTP might function as the endogenous mechanism of mild uncoupling of respiratory chain.

We compared the results of five modes of intermittent hypoxia training (IHT) on gastrocnemius muscle Po2 and heart and liver mitochondrial respiration in rats. Minutes of hypoxia, %O2, and recovery minutes on air in each mode were: 1) 5, 12%, 5; 2) 15, 12%, 15; 3) 5, 12%, 15; 4) 5, 7%, 5; and 5) 5, 7%, 15. Mode 1 proved best in that Pmo2 dropped minimally at the end of every hypoxic bout and recovered quickly after each bout. One, 2, and 3 week IHT in mode 1 each increased tissue PO2 in both normoxic and 30 min severe hypoxic (7% O2) tests. Adaptation to IHT in Mode 1 caused the substrate-dependent reorganization of liver and heart mitochondrial energy metabolism favoring NADH-dependent oxidation and improving the efficiency of oxidative phosphorylation. Mitochondrial adaptation occurred after 14 days of IHT in liver tissue, but after 21 days in myocardium, and was preserved during the 3 months following IHT termination. When using Mode 2, positive changes were also registered, but were less pronounced. Other IHT modes provoked negative effects on Pmo2 levels, both during hypoxic periods and reoxygenation. In conclusion, the most effective IHT regimen is 5 min 12% O2 with 5 min breaks, five cycles per day during 2 or 3 weeks depending on the task of IHT.

The effect of mitochondrial ATP-dependent K(+)-channel (K+(ATP)-channel) opener diazoxide (DZ) on the oxygen consumption, functional state and the opening of cyclosporine-sensitive pore in the rat liver mitochondria has been studied. It has been established that K+(ATP)-channel activation results in the increase of the oxygen consumption rate (V4(s)) and the uncoupling due to the acceleration of K(+)-cycling, the decrease in state 3 respiration rate (V3) and the respiratory control ratio (RCR). Under K+(ATP)-channel activation an inhibition of oxidative phosphorylation takes place which reduces the rate of ATP synthesis and hydrolysis as well as ATP production and consequently results in the seeming increase of P/O ratio. It has been shown that the increase in ATP-dependent K(+)-uptake accompanied by the opening of mitochondrial permeability transition pore (MPTP) leads to dramatic uncoupling of the respiratory chain due to simultaneous activation of K(+)- and Ca(2+)-cycling supported by MPTP and Ca(2+)-uniporter as well as K(+)-channels and K+/H(+)-exchange. K+(ATP)-channel activation leads to the partial inhibition of MPTP, but insufficient for the restoration of mitochondrial functions. Elimination of Ca(2+)-cycling after MPTP opening is necessary to return mitochondrial functions back to the control level which shows that MPTP could serve as the mechanism of reversible modulation of bioenergetic effects of K+(ATP)-channel activation.

The results of pharmacological correction of experimental mitochondrial dysfunction in brain stem neurons after single injection of specific respiratory complex I inhibitor rotenone by complex agents mildronate and rhytmocor have been presented. It was shown that 14-days rhytmocor injection promoted the rise of mitochondrial reserve capacity under glutamate and malate oxidation as well as under succinate oxidation. The mildronate injection was accompanied by enhancement of the velocity of phosphorilated mitochondrial respiration in the presence and absence of ADP when both substrates of oxidation were used. Under the brain stem experimental mitochondrial dysfunction, mildronate improved a decreased velocity of phosphorilated mitochondrial respiration and the respiratory control in a more significant degree under glutamate malate as the substrates of oxidation. Simultaneous increase in the respiratory control and in the coefficient of efficacy ofphosphorilation during the correction of experimental mitochondrial dysfunction by rhytmocor could suggest about essential economization of processes in mitochondrial respiratory chain. It was concluded that the main mechanisms of influence on mitochondrial disturbances of both agents were connected to the powerful rise of NAD-related oxidation which allowed to enhance a resistance of mitochondrial respiratory chain and to optimize the mitochondrial function.

Influence of prolonged immobilization (6 h strict horizontal position of rats in the tight containers daily for 2 weeks) on oxygen tension, oxygen consumption, pro-/antioxidant balance, and energetic metabolism of soft and hard periodontal tissues has been investigated. It was established that prolonged immobilization stress resulted in marked decrease in the gum tissue PO2 (36%) and in the bone tissue oxygen consumption rate (46%) compared to control. It was also determined that prolonged stress led to a reduction in the gum mitochondrial respiration rate. The latter was more expressed in case of the NAD-dependent substrate oxidation than of the FAD- dependent one. It was determined that the prolonged stress results in intensification of peroxide processes and depletion of antioxidant protection of soft tissues of periodontum. It was found that Thiotriazolin and Actovegin have modified and diminished stress-induced disorders in the soft and hard periodontal tissues oxygen homeostasis under prolonged immobilization stress.

The effect of potential-dependent potassium uptake on the transmembrane potential difference (DeltaPsi(m)) in rat brain mitochondria has been studied. It was shown that in potassium concentration range of 0-120 mM the potential-dependent K(+)-uptake into matrix leads to the increase in respiration rate and mitochondrial depolarization. ATP-dependent potassium channel (K+(ATP)-channel) blockers, glibenclamide and 5-hydroxydecanoate, block approximately 35% of potential-dependent potassium uptake in the brain mitochondria. It was shown that K+(ATP)-channel blockage results in membrane repolarization by approximately 20% of control, which is consistent with experimental dependence of DeltaPsi(m) on the rate of potential-dependent potassium uptake. Obtained experimental data give the evidence that functional activity of K+(ATP)-channel is physiologically important in the regulation of membrane potential and energy-dependent processes in brain mitochondria.

The effect of potential-dependent potassium uptake at 0-120 mM K+ on matrix Ca2+ accumulation in rat brain mitochondria was studied. An increase in oxygen consumption and proton extrusion rates as well as increase in matrix pH with increase in K+ content in the medium was observed due to K+ uptake into the mitochondria. The accumulation of Ca2+ was shown to depend on K+ concentration in the medium. At K+ concentration ≤30 mM, Ca2+ uptake is decreased due to K+-induced membrane depolarization, whereas at higher K+ concentrations, up to 120 mM K+, Ca2+ uptake is increased in spite of membrane depolarization caused by matrix alkalization due to K+ uptake. Mitochondrial K+(ATP)-channel blockers (glibenclamide and 5-hydroxydecanoic acid) diminish K+ uptake as well as K+-induced depolarization and matrix alkalization, which results in attenuation of the potassium-induced effects on matrix Ca2+ uptake, i.e. increase in Ca2+ uptake at low K+ content in the medium due to the smaller membrane depolarization and decrease in Ca2+ uptake at high potassium concentrations because of restricted rise in matrix pH. The results show the importance of potential-dependent potassium uptake, and especially the K+(ATP) channel, in the regulation of calcium accumulation in rat brain mitochondria.

Oxygen consumption, glucose blood level and liver mitochondrial respiration were investigated in male Wistar rats permanently living in middle altitude (2100 m, Elbrus region). The animals were characterized by reduced body oxygen consumption and blood glucose level, as well as by intensified utilization of NAD-dependent substrates in mitochondrial respiratory chain with increasing indices of ADP-stimulated respiration in comparison with plains rats. As a result of adaptive rebuilding of oxidative metabolism in rats--inhabitants of midlands, the nature and severity of metabolic responses to acute hypoxia were also changed. After lifting in barochamber to a "height" of 5600 m during 3 hours, plains rats transiently demonstrated hypometabolic and hyperglycemic reactions. A rapid adaptation of mitochondrial function occurred due to increase in the rate of FAD-dependent substrate oxidation accompanied by a decrease in the effectiveness of phosphorylation. In midland rats, by contrast, hypoglycemic reaction was developed, and further reduction of aerobic metabolism was limited. Rapid adaptation of mitochondrial function to acute hypoxia in those rats was more intense than in the plains animals. This was achieved by a significant increase in the rate of NAD-dependent substrate oxidation, especially lipids, and an improved efficiency of mitochondrial respiration and an increased economy of oxygen utilization.

The influence of exogenous cytochrome c on reactive oxygen species (ROS) formation and its dependence on mitochondrial permeability transition pore (MPTP) opening is studied in rat liver mitochondria. Fluorescent probe dichlorofluorescein (DCF) was used. It was shown that MPTP activation by increasing concentrations of Ca2+ in the medium results in the increase in mitochondrial ROS production and oxygen consumption, but the decrease in matrix calcium retention, dependent on the amount of added Ca2+. Cytochrome c in the incubation medium does not much influence ROS formation when MPTP opening is blocked by cyclosporine A. However, in the presence of cytochrome c MPTP opening is accompanied by dramatic increase in ROS production. Steep rise in DCF fluorescence because of matrix ROS formation is sensitive to MPTP opening and is not resulted from the direct interaction between the probe and cytochrome c outside the mitochondria. To explain obtained data the hypothesis is put forward that MPTP could serve for ROS exchange between the matrix and the medium where heme iron of cytochrome c would act as a catalytic center to enhance ROS production. We suppose that apart of its conventional function, cytochrome c which is not involved in electron transport, could serve in such way as the amplifier of ROS production which in turn would provide a background for the development of apoptosis due to MPTP opening.

Male Wistar rats were exposed to periodic hypobaric hypoxia (PHH), by "lifting" in barochamber at "altitude" 5600 m for 1 h every 3 days (6 séances). The dynamics of changes in oxygen consumption (VO2), and body temperature (Tm), as well as in HIF-1alpha and HIF-3alpha gene expression, and mitochondrial respiration in the ventricles of the heart was studied. On the basis of the data we identified four phases of the physiological changes. The first phase, hypometabolic (1-3 séances), is characterized by decrease in VO2 and Tm, induction of HIF-1alpha and HIF-3alpha with delayed transient stimulation of metabolism in response to each séance of hypoxia. In heart mitochondria, V3 and V4 are increased, but V3/V4 and ADP/O are reduced. During the second phase, transitional (3-4 séances), there is reorganization of metabolism and decrease its hypoxic reactivity. The third phase, hypermetabolic (4-5 séances), is characterized by intensification of metabolism and compensation of hypoxic disorders. The fourth phase (after 5 séance) - is a state of metabolic adaptation with normalization of VO2 and Tm, expression of HIF-1alpha and HIF-3alpha, mitochondrial respiration, increased NAD-dependent oxidation of carbohydrate and lipid substrates. Thus, during PHH consequent rebuilding of processes of oxygen transport, tissue respiration and thermogenesis occurs, mediated by induction of the HIF subunits.

The influence of the K+(ATP)-channel opener diazoxide on the K+ cycle and oxygen consumption has been studied in rat liver mitochondria. It was found that diazoxide activates the K+(ATP)-channel in the range of nanomolar concentrations (50-300 nM, K(1/2) ~ 140 nM), which results in activation of K+/H+ exchange in mitochondria. The latter, in turn, accelerates mitochondrial respiration in respiratory state 2. The contribution of K+(ATP)-channel to the mitochondrial potassium cycle was estimated using the selective K+(ATP)-channel blocker glibenclamide. The data show that the relative contribution of K+(ATP)-channel in the potassium cycle of mitochondria is variable and increases only with the decrease in the ATP-independent component of K+ uptake. Possible mechanisms underlying the observed phenomena are discussed. The experimental results more fully elucidate the role of K+(ATP)-channel in the regulation of mitochondrial functions, especially under pathological conditions accompanied by impairment of the mitochondrial energy state.

The influence of potassium ions on calcium uptake in rat liver mitochondria is studied. It is shown that an increase in K+ and Ca2+ concentrations in the incubation medium leads to a decrease in calcium uptake in mitochondria together with a simultaneous increase in potassium uptake due to the potential-dependent transport of K+ in the mitochondrial matrix. Both effects are more pronounced in the presence of an ATP-dependent K+-channel (K+(ATP)-channel) opener, diazoxide (Dz). Activation of the K+(ATP)-channel by Dz alters the functional state of mitochondria and leads to an increase in the respiration rate in state 2 and a decrease in the oxygen uptake and the rate of ATP synthesis in state 3. The effect of Dz on oxygen consumption in state 3 is mimicked by valinomycin, but it is opposite to that of the classical protonophore uncoupler CCCP. It is concluded that the potential-dependent uptake of potassium is closely coupled to calcium transport and is an important parameter of energy coupling responsible for complex changes in oxygen consumption and Ca2+-transport properties of mitochondria.

The experiment, on Wistar male rats was carried out to investigate influence of endurance training (swimming with load 7.0 +/- 1.3% body weight, 30 min a day, during 4 weeks) and additional intermittent hypoxic training (12% O2 in N2 - 15 min, 21% O2 - 15 min, 5 sessions a day, during the first 2 weeks) on the following parameters: ADF-stimulated mitochondrial respiration, lactate/pyruvate ratio, succinate dehydrogenase activity, and lipid peroxidation in skeletal muscle. The next oxidation substrates were used: 1 mmol/l succinate and 1 mmol/l alpha-ketoglutarate as well as the next inhibitor succinate dehydrogenase 2 mmol/l malonate. It was shown that physical work combined with intermittent hypoxic training led to the increase of mitochondrial respiration effectiveness in muscle energy supply under alpha-ketoglutarate oxidation in comparison with succinate oxidation as well as to the decrease of succinate dehydrogenase activity and lipid peroxidation. The study suggested that these changes may correct mitochondrial dysfunction under intensive muscular work.

The aim of this study was to investigate physical endurance, maximal oxygen uptake, oxygen partial pressure, and pH in blood and skeletal muscle as well as the muscle metabolic parameters (lactate and pyruvate concentration, lactate/pyruvate and NAD/NADH ratios, succinate dehydrogenase activity, ADP-stimulated mitochondrial respiration) under various regimen of combination of endurance training with intermittent hypoxic training (IHT) in adult Wistar rats. It was shown that physical endurance, maximal oxygen uptake, and muscle PO2 (PmO2) were maximally increased in those animals who simultaneously underwent endurance training and IHT. The same animals demonstrated the minimal decrease in PmO2, blood and muscle pH under testing intensive physical workload. The latter led to the lesser shifts in metabolic parameters in the muscle of rats adapted both to IHT and endurance training than in rats adapted to endurance training only. The combined effects of IHT and adaptation to load hypoxia resulted in an increase of the role of NADH - oxidation pathway in the mitochondrial energy production.

It NO has been shown play to the primary role in several mitochondrial functions. Our aim for this study was to investigate whether exogenous NO (L-arginine) or NO blocker L-NNA modulated the adaptive reactions of rat myocardial tissue respiration on intermittent hypoxic training (IHT). In the control rats an acute hypoxic test (inhalation of 7% O2, 30 min) provoked sharp augmentation of ADP-stimulated tissue respiration with the increase of respiratory coefficient and phosphorylation rate, the decrease of O2 uptake efficacy and switching the energy supply to succinate oxidation pathway. The same hypoxic test but following 14 days of IHT (11% O2, 15-min sessions with 15 min rest intervals, 5 times daily) produced a stimulation of oxidative phosphorylation with primary activation of NAD-dependent pathway, the marked increase of ADP/O ratio. The combination of IHT with L-arginine treatment (600 mg/kg intraperitoneally, daily before IHT sessions) provoked the decrease of tissue oxygen consumption in comparison with untrained animals. L-arginine effects abolished by the NO-synthase blocker L-NNA. Its effects on mitochondrial function deals with succinic acid inhibition utilizatin (increasing level ADP/O) and activation NADH-dependent oxidation. We conclude that the combination of IHT with NO-precursor treatment was capable to increase significantly the tolerance to episodes of acute hypoxia.

It have been shown that NO plays primary role in several mitochondrial functions. Our objective for this study was to investigate whether exogenous NO (L-arginine) modulates the adaptive reactions of rat liver tissue respiration and lipid peroxidation on intermittent hypoxic training (IHT). In control animals the test with acute hypoxia (7% O2, 30 min) provoked sharp augmentation of ADP-stimulating tissue respiration with the increase of respiratory coefficient and phosphorylation rate, the decrease of O2 uptake efficacy and switching the energy supply to succinate oxidation pathway with the inhibition of aminotranspherase Krebs cycle substrates supply mechanism. The twice augmentation of malon dialdehyde content (MDA) was observed. The same hypoxic test but after 14 days of IHT (11% O2, 15-min sessions with 15 min rest intervals, 5 times daily) produced a stimulation of oxidative phosphorylation with primary activation of aminotranspherase pathway, the marked increase of ADP/O ratio on the background of a decrease of MDA content by 32%. The combination of IHT with L-arginine treatment (600 Mg/Kg intraperitoneally, daily before IHT sessions) provoked a decrease of tissue oxygen consumption, the inhibition of both aminotranspherase and succinateoxidase Krebs cycle substrates supply mechanism on the background of pronounced MDA decrease (by 120%) in comparison with untrained animals. L-arginine effects abolished by the NO-synthase blocker L-NNA. We conclude that the combination of IHT which promotes the increase of inner adaptive mechanisms with NO-donors treatment could significantly increase the tolerance to episodes of acute hypoxia.

Osteodystrophy models consisted in removing weight loading from hind limbs and rats' immobilization; disturbances in bone oxygen uptake were quelled by induced gaseous environment with low PO2. Unloading of the hind limbs for 28 days was found to decrease oxygen uptake by fragments of the iliac bone, and oxygen pressure in m. gastrocnemius. These parameters were unchanged in atmosphere with 12% of oxygen. Motor restraint of rats in hypoxic atmosphere leads to less marked reductions in oxygen demand in iliac fragments and oxygen pressure in m. gastrocnemius as compared with breathing ambient air.

The activities of Na+, K(+)-ATPase and 5'-nucleotidase of the plasma membranes, Ca++, Mg(++)-ATPase of the sarcoplasmic reticulum, mitochondrial cytochrome C-oxidase and succinate dehydrogenase were investigated in the brain, liver and gastrocnemius muscle of Wistar rats at various terms of adaptation to hypoxic hypobaric intermittent hypoxia. An increase in the activity of Na+, K(+)-ATPase and mitochondrial enzymes (mostly in the liver) as well as in the activity of Ca++, Mg(++)-ATPase in the skeletal muscle beginning from 14 days of adaptation have been shown. Starting with the same term the authors have registered the less marked changes of the enzymic markers of cell membranes in adapted rats under additional acute and severe hypoxic test when compared to unadapted animals. Possible changes in the regulation of membrane-bound enzyme activity during the process of adaptation to hypoxic hypoxia have been discussed.

Chenophalk (chenodeoxycholeic acid) was given to Wistar rats, including intact animals and those with chronic toxic hepatitis, in daily oral dose of 15 mg/kg body weight during 11 days. Chronic toxic hepatitis was induced by 7 subcutaneous injections of carbon tetrachloride (0.3 ml of 50% oil solution per kg body weight) each three days. Chenophalk was shown to impair bile crystallization. It enhanced demethylase activity, elevated the levels of cytochromes P-450 and b5 in the liver microsomal fraction, and decreased lipid peroxidation just after injection. The agent normalized oxygen tension in the liver tissue, which had been reduced by carbon tetrachloride. Chenophalk caused disturbances in the structure of the liver and in microcirculation early after injection, showing a tendency to normalize the histostructure of the liver.

The chronic hepatitis in Wistar rats was induced by seven subcutaneous injections of carbon tetrachloride (0.3 ml of 50% oil solution per 1 kg of body mass) made each third day. It was shown that cytochromes P-450 and b5 content, demethylase activity in the liver microsomal fraction as well as the oxygen tension in the liver tissue were decreased, while lipid peroxidation was intensified. The PHA-induced blood lymphocyte blastogenesis was inhibited and concentration of circulating immune complexes in the blood was higher than that in intact animals.

The membrane activity of Na+, K(+)-ATPase, Mg2+, Ca(2+)-ATPase, mitochondrial NAD-isocitrate dehydrogenase, mitochondrial and cytosolic L-glycerol-3-phosphate dehydrogenase was determined in the liver and brain of Wistar rats under acute hypoxic hypoxia against the background of preventive taurine administration. It was shown that preliminary taurine treatment prevented a decrease of hypoxia in activity of Na+. K(+)-ATPase and mitochondrial calcium-dependent enzymes, mostly in the liver. Changes in the intracellular calcium content and biomembrane structure have been discussed as the mechanisms of the taurine effect on the enzymes' activity.

It is shown that preliminary taurine treatment prevents the disturbances of energy metabolism in the brain, heart and liver tissues of Wistar rats with acute hypoxic hypoxia. Administration of taurine restored to normal the parameters of adenine pool: the concentration of ATP increased within the cytoplasm, while that of ADP and AMP diminished; mitochondrial respiration proceeded more rapidly; the concentrations of pyruvate and malate decreased; isocitrate dehydrogenase activity, P/O and NAD/NADH ratios increased. Taurine treatment resulted in a decreased level of lipid peroxides in the rat tissues with hypoxia. The role of intracellular calcium content and biomembranes structure changes as the mechanisms of taurine action on energy metabolism and lipid peroxidation is discussed.

It is stated that prophylactic administration of ional (dibunol) and taurine to rats exerts an antihypoxic effect in case of acute hemic hypoxia. It is expressed in a decrease of methemoglobin level in blood, increase of pO2, in the skeletal muscles, normalization of the structure of hematoparenchymatous barriers, prevention or decrease in a fall of the rate of oxygen consumption by tissues.

The experiment was done on rabbits which were fed for 4-5 weeks a diet with sunflower oil or butter (0.2 gm/100 gm of weight). It was shown that oxygen supply of skeletal muscle could change due to structural of functional modifications of hepato-parenchymatous barrier caused by dietary factors.

Peculiarities of oxygen supply of a skeletal muscle under normal alimentary conditions and under conditions of alimentary starvation have been studied on spontaneously hypertensive rats (SHR) and normotensive rats (NTR). Calculations of oxygen permeability through hematoparenchymatous barrier (HPB) have shown that it is higher (by 26%) in SHR than in NTR. This difference can be a result of higher content of arachidonic acid and intensity of lipid peroxidation in phospholipids of plasma membranes. After 5-day starvation tension of O2 in skeletal muscle of SHR increased due to a decrease of oxygen demand and increase of oxygen permeability through HPR. The observed modification of fatty-acid spectrum of plasma membrane phospholipids and a sharp decrease of cholesterol content in them can be responsible for an increase of oxygen permeability through HPB.

Experiments were conducted on rats with high and low reactivity of the respiratory system to study the effect of starvation in tests with a hypoxic gas mixture containing 11% O2. Rats with high reactivity were more sensitive to starvation. Animals with low reactivity were marked by a more resistant regulation of energy metabolism, which was evidence of the significant role of individual reactivity of rats to reduced oxygen partial pressure in the inhaled gas mixture. The higher level of O2 tension in the muscle in unaltered oxygen consumption in rats with low reactivity after fasting for 3 days and breathing air may be the results of growth of the oxygen diffusion coefficient.

The data obtained suggest that an increasing oxygen permeability of hematoparenchymatous barrier is a result of structural and chemical changes of biomembranes in rabbits after 7 days of starvation. A significant increase in desaturation of lipids and phospholipids, a decrease of cholesterol level in cytoplasmic and basal membranes were shown along with modifications of vascular endothelium of a metabolic type.

The 5-day starvation, with water ad libitum, decreased the reactivity of the respiration system to acute hypoxic hypoxia (11% O2) in spontaneously hypertensive (SH) rats and had no such effect in Krushinskiĭ-Molodkina (KM) rats. The difference in the responses of KM and SH rats to starvation and the action of hypoxic gas mixture shows that the respiratory system reactivity has an obvious genetic component.

Individual variations of the respiratory system reactivity have been studied in experiments on rats. It is shown expedient to estimate reactivity of the respiratory system to hypoxic hypoxia by the pattern of changes in the total oxygen uptake. Animals demonstrating no essential changes in the oxygen uptake in response to hypoxia (11% O2) are referred to individuals with high reactivity of the respiratory system; those responding by a drastic decrease in the oxygen uptake--to animals with low reactivity of the respiratory system. A strong correlation is determined between the respiratory system reactivity and individual resistance of organism to acute hypoxic hypoxia.

In 25 rabbits with local anesthesia, recordings of partial oxygen pressure in the hindlimb arterial and venous blood, oxygen tension in muscles and some other parameters followed by calculation of the muscle hematoparenchymatous barrier, revealed that, in inhalation of normoxic helio--oxygen mixture, the hematoparenchymatous barrier's diffusion capacity for oxygen increases as compared with the analogous value in breathing with air. In inhalation of hypoxic helio--oxygen and nitrogen--oxygen mixtures (11% O2), the barrier's diffusion capacity for oxygen proves higher than in breathing with respective normoxic gas mixtures. A possible pharmacological effect of helium influence upon plasmatic membranes of the hematoparenchymatous barrier's components is discussed.

Animals with high, low and medium resistance to hypoxia were selected by repetitive tests under a vacuum bell. It has been shown that most rats with high resistance to hypoxia are characterized by strong basic nervous processes. The majority of animals with low resistance and all the animals with medium resistance to hypoxia exhibit signs of the weak type higher nervous activity.

Alimentary conditioned reflexes in the form of pressing (with an effort not less than 600 g) with a fore-leg on the pedal of a nearby feeding-trough, were elaborated by means of classical secretory technique in 15 dogs with defined typological characteristics of the higher nervous activity. The motor habit was formed in about a half of the animals. The ability to instrumental learning was assessed on a five-points scale in accordance with four stages of habit formation. The study revealed an absence of direct dependance between the obtained typological characteristics of the animals and their ability to instrumental conditioning.

In 21 rabbits, the process of oxygen mass transfer through the hemato-parenchymatous barrier conditions of hyperoxia with 80% O2 in inhaled mixture, was shown to decrease 6-7-fold and to be determined by a high partial O2 pressure rather than physical properties of accompanying gas. The protective properties of hyperbarism are equally evident both in nitrogen-oxygen and in helium-oxygen mixtures, restricting the increment of O2 tension in tissues.