Activity of liver monooxygenase system in rats with low and high resistance to hypoxia

Rats with low and high resistance to hypoxia are shown to differ in terms of the baseline activity of liver monooxygenases bothin vivo andin vitro. Low-resistance animals are characterized by a significantly higher rate of elimination of antipyrine, hexenal, and nifedipine, as evidenced by shorter half-elimination period and higher urinary concentration of metabolites. The concentration of microsomal cytochromes P-450 and b5 as well as the rates of N-demethylation of amidopyrine, p-hydroxylation of aniline, and hydroxylation of diazepam are considerably higher in rats with low resistance to hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 9, pp. 291–294, September, 1996     

Effects of adaptation to hypoxia on cytochrome levels in the brain and liver of rats

After a prolonged (for 30 days) adaptation of rats to intermittent hypoxia, their brains contained lowered levels of mitochondrial cytochromes, despite an increase in the number of mitochondria in the brain tissue mass, along with similar levels of high-energy compounds and more protein as compaired to the brains of unadapted controls. A mitochondrial population with novel properties presumably emerged in the brain. These effects were all more strongly marked in rats with an initially low resistance to hypoxia. In the liver of hypoxiaadapted animals, unlike in their brain, cytochrome levels in the mitochondrial and microsomal redox chains were lowered and the biogenesis of mitochondria was much less intensive. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 576–579, December, 1995     

Role of glycolysis in the maintenance of the energy-synthesizing function of hepatocytes from rats adapted and nonadapted to hypoxia at different oxygen concentrations

It is demonstrated that the lactate-Po₂ dependence is the same in hepatocytes of rats with high and low resistance to hypoxia and does not correlate with phasic changes in the ATP concentration in the 890–50 μM O₂ region. Strong activation of lactate formation against the background of ATP decrease indicates that glycolysis is not the major mechanism determining the steady-state ATP level in the cell and affecting the ATP-Po₂ relationship in a wide range of oxygen concentrations. The intensity of glycolysis in hepatocytes of rats with high resistance to hypoxia is markedly increased after periodic adaptation to hypoxia but remains practically unchanged in the hepatocytes of low-resistance rats. This indicates that fundamentally different compensatory mechanisms are involved in this process in the liver of high- and low-resistance rats. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 119, N ^o 1, pp. 28–32, January, 1995     

Behavioral peculiarities and reactions of brain dopaminergic systems in rats with different resistance to acute hypobaric hypoxia

Locomotor activity in the open field test did not correlate with rat resistance to acute hypobaric hypoxia; there was a correlation between this resistance and rat behavior during acute stress. Immobility was characteristic of rats with low and particularly medium resistance to hypoxia; this reaction can be abolished by antidepressants. By contrast, highly resistant rats were mainly hyperactive. The resistance to hypoxia was associated with extreme parameters of dopaminergic neuron functioning. In low-resistant rats locomotor stereotypia was maximal, while perioral stereotypia was the minimal; highly resistant rats were characterized by an opposite pattern, and medium-resistant rats occupied an intermediate position. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 9, pp. 275–278, September, 2000     

Effect of hypoxia of increasing severity on the dynamics of cerebral cortex EEGs in rats with different resistance to acute oxygen deficiency

EEGs recorded from the cerebral cortex of rats with high and low resistance to hypoxia during “elevation” in a pressure chamber differ in the dynamics of the EEG power spectra. EEGs of highly resistant rats show phasic changes in biopotentials correlating with the severity of hypoxia: primary increase in the absolute power of all frequency ranges is followed by normalization and a secondary increase with predominance of the slow-wave component, inhibition of the β₂ range and the emergence of interhemispheric differences, and terminal inhibition of the power of all frequency ranges. In rats with low resistance to hypoxia, phases of relative normalization of EEG spectra and their depression during terminal period are not observed, all changes being represented by a continuous increase in the power of the α and δ ranges with progressive inhibition of the β₂ range and then of the β₁ range. Interhemispheric asymmetry is significant throughout the period of power increase. A high amplitude burst activity is recorded in rats of both types starting from an altitude of 8000 or 9000 m. The pattern of EEG changes in rats exposed to hypoxia of growing severity consistently reproduces those observed in patients with ischemic stroke. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 9, pp. 262–267, September, 1996     

Individual resistance of the organism and nerve cell to hypoxia

The correlation between the pattern of a neuron's reaction to acute hypoxia and individual resistance to oxygen deficit is studied on ratsin vivo as well as on surviving slices of their cerebellumin vitro. According to the survival time in a pressure chamber simulating an altitude of 11 km all the rats were divided into groups of high resistance, medium resistance, and low resistance to hypoxia. Survival time was 4.2 times longer in the high resistance group than in the low resistance group. In the cerebellar slices of high resistance animals 61.5% high-resistance neurons and 38.5% low-resistance neurons were recorded. On the other hand, in the high resistance animals the percentage of high-resistance neurons and low-resistance neurons was 31.2 and 68.8, respectively. The period of hypoxia development was 4.32 times longer in the high-resistance neurons as compared to low-resistance neurons. It is speculated that individual differences in the resistance to O₂ deficit are of a hereditary nature and manifest themselves not only on the level of the whole organism, but also in the individual nerve cell. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 11, pp. 454–457, November, 1994     

Blood corticosterone and resistance to hypoxia during operant conditioning and development of learned helplessness

Operant conditioning under conditions of uncertain behavioral environment was accompanied by a significant elevation of blood corticosterone, high exploratory activity, and increased resistance to hypoxia. The blood content of corticosterone and exploratory activity significantly decreased in rats developing learned helplessness, but their resistance to hypoxia increased in comparison with that during learning. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No.7, pp. 29–31, July, 1999     

Effects of adaptation to intermittent hypoxia on oxidative phosphorylation in brain mitochondria of rats with different sensitivities toward oxygen deficiency

After long-term adaptation to intermittent hypoxia, rats with an initially low resistance to acute oxygen deficiency were 2 to 4 times more resistant to it, while highly resistant rats did not show a significant change in resistance. The adaptation was accompanied by weakening of the electron-transporting function of the respiratory chain and increasing efficiency of oxidative phosphorylation in the brain mitochondria oxidizing NAD-dependent substrates, indicating that energy was produced in a more economical way. The succinate oxidase pathway of oxidation was found to be utilized to only a limited extent as a compensatory mechanism in animals exposed to intermittent hypoxia over a prolonged period. The effects of adaptation were more marked in the brain mitochondria of rats initially highly sensitive to oxygen deficiency. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 572–575, December, 1995     

Pharmacokinetics of antipyrine in rats with different resistance to hypoxia in cold stress

It is shown that the parameters of antipyrine pharmacokinetics during cold exposure depend on individual resistance to hypoxia. High-resistant rats are characterized by less intense metabolism and more rapid normalization of pharmacokinetic parameters than lowresistant rats characterized by shortened elimination half-time corresponding to a more rapid metabolism of xenobiotics under conditions of cold stress. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 126, No. 11, pp. 513–515, November, 1998     

Lipid peroxidation parameters in the internal organs of rats with different degrees of resistance to hypoxia

Lipid peroxidation and the antioxidant system of the heart, liver, and brain are studied in adult male Wistar rats with high and low resistance to hypoxia tested by “raising” to an altitude of 11.5 km and in intact outbred rats. These parameters are found to be the same in the brain of low- and high-resistance rats, while the brain content of lipid peroxidation products is higher in both groups of Wistar rats compared with outbred rats. The heart and liver parameters are coupled to the resistance to hypoxia. Antioxidant activity prevails over lipid peroxidation in the hearts and livers of high-resistance rats, confirming that oxidation plays a major role in the damaging and lethal effects of acute hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 1, pp 26–29, January, 1996 Presented by A. I. Archakov, Member of the Russian Academy of Medical Sciences     

Antihypoxic effects of derivative on the EEG power spectra in rats with different susceptibility to oxygen deficiency

The succinate-containing hydroxypyridine derivative yancarb increases both the altitude tolerated by rats and their survival time at a high altitude, particularly in rats with low resistance to hypobaric hypoxia; it also prevents both phasic changes in the EEG characteristic of hypobaric hypoxia and hemispheric asymmetry and paroxysmal activity in the brain of highly resistant rats in the 5000–10,000 m range and in rats with low resistance in the 5000–11,000 m range. Antihypoxic effects of this substance are more pronounced in low-resistance rats and in the left hemisphere of both high- and low-resistant animals; in altitude range of 10,000–13,000 m these effects are weaker or absent. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 7, pp. 57–62, July, 1997     

Effects of adaptation to periodic hypoxia on kinetic parameters of respiratory chain enzymes in rat brain

A study of kinetic parameters of brain respiratory enzymes revealed that the maximal velocity and the Michaelis apparent constant for NADH-cytochrome C-reductase are significantly lower in low-resistant rats than in rats with a high resistance to hypoxia. Adaptation to periodic hypoxia increases total resistance only in low-resistant rats. It is accompanied by an increase in the values of kinetics parameters for NADH-cytochrome C-reductase and cytochrome oxidase. Kinetic parameters for these enzymes in the brain of high-resistant rats are either unaltered or even decreased. It is suggested that the first enzymatic complex of the respiratory chain is one of the limiting or regulating links in energy metabolism determining the brain's resistance to hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 3, pp. 252–255, March, 1996.     

Effect of acute hypoxia on resistance to hypoxia in rats

The resistance of rats to hypoxia was measured by survival time after exposure to high-altitude (11.5 km) hypoxia. The first exposure to acute hypoxia caused phasic changes in the survival time: short-term in high-resistant rats (about 24 h) and long-term in moderate- and lowresistant rats (38–39 days) starting from 1 h and 6–7 days after the first exposure, respectively. Adaptive reactions were more pronounced in low- and moderate-resistant rats, while disadaptation was typical of high-resistant animals. In all rats, the adaptive effect dominated until days 22–23. Throughout the testing, the initial type of resistance was retained in 79% of high-resistant rats, in 41% of low-resistant and in 33% of moderate-resistant rats, i. e., the initially homogenous groups formed after the first exposure in accordance with the type of resistance became mixed, which reduced the intergroup differences. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 6, pp. 625–628, June, 1999     

Evaluation of microsomal and mitochondrial oxidation in rat liver in tetracycline-induced hepatosis

A satistically significant decrease in the content of cytochromes P-450 and b₅ and in the activity of aniline hydroxylase and p-nitroanisole demethylase occurs in rat liver microsomes during the development of experimental acute fatty hepatosis develoing within a 24-h period after intraperitoneal administration of 125 mg/kg tetracycline hydrochloride. Under these experimental conditions tetracycline hydrochloride elicits only an insignificant disintegrating effect on oxidative phosphorylation in liver mitochondria. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 12, pp. 612–615, December, 1994     

Changes in hypoxia resistance in rats during daytime

The resistance to acute hypoxia in male Wistar rats was evaluated by the period of survival after exposure to high-altitude hypoxia (11.5 km above see level). The study was performed during daytime (13.00–21.00) in autumn. The fatal rat population was characterized by the log-normal distribution of survival periods. The rats with low and moderate resistance to hypoxia exhibited similar diurnal variations in it with gradual decrease by the end of daytime more pronounced in low-resistant rats. The rats with high resistance showed relatively constant resistance to hypoxia which decreased only at 21:00. All groups revealed a relatively stable resistance to hypoxia from 16:00 to 18:00. These variations in the resistance to hypoxia should be taken into consideration when planning experimental research. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 3, pp. 256–260, March 1999     

Comparison of lipid peroxidation parameters in the heart,liver, and brain of rats with different degrees of resistance to hypoxia

The relationship between the intensity of lipid peroxidation and the activity of the antioxidant system in the heart, liver, and brain is studied in male Wistar rats with low and high resistance to hypoxia tested by being “raised” to an altitude of 11.5 km and in intact outbred rats. It is found that in all groups of rats the content of lipid peroxidation products is highest in the liver, lower in the heart, and lowest in the brain. In all groups, the rate of the ascorbate-induced lipid peroxidation is highest in the brain, lower in the liver, and lowest in the heart. The activity of the antioxidant system is highest in the brain, lower in the liver, and lowest in the heart of low-resistance and outbred rats, while in high-resistance rats it is the same in all the organs. Thus, the difference in the parameters of lipid peroxidation and, particularly, of the antioxidant system in the studied organs is most pronounced in rats with a low resistance to hypoxia. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 121, N ^o 2, pp. 138–143, February, 1996 Presented by A. I. Archakov, Member of the Russian Academy of Medical Sciences     

Experimental study of the possibility of metabolic correction of maternal, fetal, and newborn hypoxia in rats using a new amino acid composition MR-33

The status of pregnant rats, their fetuses, and progeny exposed to oxygen insufficiency are compares. By the end of pregnancy the resistance to hypoxia markedly decreases. Newborn rats during nursing are highly resistant to hypoxia. When nursing period is over, the resistance to hypoxia drops, but later is gradually restored. MR-33 preparation produces a pronounced antihypoxic effect. Administration of the drug to pregnant rats not only appreciably improves their resistance to oxygen insufficiency, but also promotes adaptation and compensatory mechanisms in the progeny, thus helping the progeny to better tolerate hypoxia, particularly when its probability is particularly high. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 10, pp. 451–454, October, 1997     

Effect of atp and cocarboxylase on activity of malate dehydrogenase and its isozymes in blood serum and myocardium

Changes in the activity of malate dehydrogenase (MD) and its isozymes in the blood serum and heart muscle of rats were investigated during hypoxia and under the influence of ATP and cocarboxylase. An additional cathodic isozyme (MD₄) appeared in the blood serum during hypoxia. Under the influence of ATP and cocarboxylase the metabolic changes in the blood and myocardium induced by hypoxia did not correlate fully.Presented by Academician of the Academy of Medical Sciences of the USSR A. A. Vishnevskii.Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 80, No. 8, pp. 48–50, August, 1975.     

Adaptation to periodic high-altitude hypoxia inhibits baroreflex vagal bradycardia in rats

A 3-week course of adaptation to high-altitude hypoxia (4500 m above sea level) inhibited baroreflex avagal bradycardia induced by a rapid rise of systemic blood pressure in conscious rats. Bradycardic responses to electrical stimulation of peripheral end of the right vagus nerve and methacholine (M₂ muscarinic receptor agonist) in hypoxia-adapted rats did not differ from the control. It is concluded that hypoxia inhibits baroreflex vagal bradycardia by acting on a central element of the baroreceptor reflex arch Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 4, pp. 386–389, April, 2000     

Phrenic artery blood flow under loaded respiration

Acute experiments on anesthetized cats with additional resistive loads to inspiration and/or expiration revealed adequate changes in vascular bed resistance and blood flow rate in the phrenic artery. The increase in the phrenic artery blood flow during airflow resistive loading by 30–40 mm H₂O was similar to the, changes previously found for inspiration of gas mixtures containing 5% O₂ and 5% CO₂. Minute ventilation increased 2 times under hypoxia and 3.5 times under hypercapnia. This index did not change under additional loading. Translated fromByulleten' Eksperimental'noi Biologii I Meditsiny, Vol. 125, No. 1, pp. 18–22, January, 1998.