[The modification of nitric oxide production by exogenous substrates of Krebs cycle during acute hypoxia].

Hypoxia causes the disruption of mitochondria electron respiratory chain, production of active oxygen forms and the unoxidative protection. In experiments on Wistar rats the influence of sodium succinate (50 mg/kg) and 6-ketoglutarate (200 mg/kg) on NO2-, NO3-, urea and polyamines contents in blood and liver under acute hypoxia (7% O2 in N2, 30 min) was investigated. Nitrite and nitrate content decreased in erythrocytes and liver but not in plasma under acute hypoxia. The exogenous succinate (SK) stimulated production of nitric oxide in erythrocytes and liver while 6-ketoglutarate (KG) only in liver. The switch from more intensive SK oxidation that reveals adrenomimetic influence and causes the synthesis and release of NO from erythrocyte, to less intensive KG correlates with well-known decrease of tissue respiration under the activation of the cholinergic system due to urea cycle activation particularly in liver. The activation of the SK oxidation takes place mainly under the different stress conditions and causes NO production in the blood cells. These conditions of the intensive and fast action under acute hypoxia are accompanied on the one hand by the increase of oxygen input ratio and on the other hand by activation of the free radical oxidation. The protective effect of the natural Krebs cycle intermediates--SK and KG in particular, is related to the regulation of NO synthesis and its metabolism in the main organs. These results proved the existence not only metabolite control of NO system by Krebs cycle intermediates, but the existence of the systemic mechanism for the support of the functional state of mitochondria under hypoxia.

[Effect of intermittent hypoxic hypoxia on energy supply of rat skeletal muscle during adaptation to physical load].

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.

[Myocardium mitochondria functional state during adaptation to intermittent hypoxia and treatment with L-arginine]. / Funktsional'nyi stan mitokhondrii miokarda shchuriv za adaptatsiï do interval'noï hipoksiï pid vplyvom L-arhininu.

Processes of respiration and oxidative phosphorylation in myocardium mitochondria after 14 days of intermittent hypoxia training method (IHT) and IHT with L-arginine (600 mg/kg) as a precursor of nitric oxide have been investigated. ADP-stimulated respiration (under 0.35 mM succinate, 1 mM alpha-ketoglutarate, inhibitor of succinate dehydrohenase--2 mM malonate and inhibitor MFC I 10 microM rothenone) have been studied. The intensivity of lipid peroxidation processes was studied under the increase of 2-thiobarbituric acid products in blood and myocardium. Our investigations deal with the valuation of dynamic support of myocardium mitochondria functional parameters (respiration control by Chance, respiration rate, efficiency of phosphorylation) on 1, 30, 60 and 180th days after the last adaptation terms. It has been shown that the preservation of the main NAD-dependent substrates of mitochondria respiratory chain oxidation is the basis for increasing functional efficiency in myocardium mitochondria after the adaptation. The changes were accompanied by the decrease of lipid peroxidation processes. These effects were intensified under L-arginine treatment during IHT.

[Effect of K-ATP channel opener-pinacidil on the liver mitochondria function in rats with different resistance to hypoxia during stress]. / Vplyv aktyvatora K-ATP kanaliv-pinatsydylu na funktsionuvannia mitokhondrii pechinky shchuriv iz riznoiu rezystentnistiu do hipoksiï za stresu.

We have examined the influence of ATP-sensitive potassium (KATP) channel opener pinacidil (0.06 mg/kg) and inhibitor glibenclamide (1 mg/kg) on the changes of energy metabolism in the liver of rats under the stress conditions. The rats were divided in two groups with high and low resistance to hypoxia. The stress was modeled by placing the rats in a cage filled with water and closed with a net. The distance from water to the net was only 5 cm. The effects of KATP opener pinacidil (0.06 mg/kg) and inhibitor glibenclamide (1 mg/kg) on ADP-stimulating mitochondrial respiration by Chance, calcium capacity of organellas and processes of lipid peroxidation in the liver of rats with different resistance to hypoxia under the stress condition have been investigated. We have used the next substrates of oxidation: 0.35 mM succinate and 1 mM alpha-ketoglutarate. The additional analyses were conducted with the use of inhibitors: mitochondrial enzyme complex I 10 mM rotenone and succinate dehydrohenase 2 mM malonic acid. It was shown that the stress condition evoked the succinate oxidation and the decrease of alpha-ketoglutarate efficacy, the increase of calcium mitochondrial capacity and the intensification of lipid peroxidation processes. Under the presence of succinate, the increase of O2 uptake with simultaneous decrease of ADP/O ratio in rats with high resistance under stress was observed. Simultaneously, oxidation of alpha-ketoglutarate, a NAD-dependent substrate, was inhibited. Pinacidil caused the reorganization of mitochondrial energy metabolism in favour of NAD-dependent oxidation and the improvment of the protection against stress. The decrease of the efficacy of mitochondrial energy processes functioning was shown in animals with low resistance to hypoxia. KATP channel opener pinacidil has a protective effect on the processes of mitochondrial liver energy support under stress. These changes deal with the increase of alpha-ketoglutarate oxidation (respiratory rate and ADP/O) and the decrease of lipid peroxidation processes. We concluded about protective effect ofpinacidil on mitochondrial functioning under stress.

[Role of ATP-sensitive potassium channel activators in liver mitochondrial function in rats with different resistance to hypoxia]. / Rol' aktyvatoriv ATP-chutlyvykh kaliievykh kanaliv u funktsionuvanni mitokhondrii pechinky shchuriv iz riznoiu rezystentnistiu do hipoksiï.

Effects of ATP-sensitive potassium (KATP) channels opener pinacidil (0.06 mg/kg) and inhibitor glibenclamide (1 mg/kg) in rats with different resistance to hypoxia on indices of ADP-stimulation of mitochondrial respiration by Chance, calcium capacity and processes of lipid peroxidation in liver has been investigated. We used next substrates of oxidation: 0.35 mM succinate, 1 mM alpha-ketoglutarate. Additional analyses contain the next inhibitors: mitochondrial fermentative complex I-10 mkM rotenone, succinate dehydrogenase 2 mM malonic acid. It was shown that effects of pinacidil induced the increasing of oxidative phosporylation efficacy and ATP synthesis together with lowering of calcium capacity in rats with low resistance to hypoxia. Effects of pinacidil were leveled by glibenclamide. These changes are connected with the increasing of respiratory rate, calcium overload and intensification of lipid peroxidation processes. A conclusion was made about protective effect of pinacidil on mitochondrial functioning by economization of oxygen-dependent processes, adaptive potentialities of organisms with low resistance to hypoxia being increased.

[Tricarboxylic acid cycle in energy metabolism and antioxidant cell defense in acute hypoxia]. / Rol' tsyklu trykarbonovykh kyslot u protsesakh enerhozabezpechennia ta antyoksydantnoho zakhystu klityn pry hostrii hipoksiï.

The object of this study was to investigate the effects of exogenous succinate (SC) and alpha-ketoglutarate (KGL) on intensity of NO metabolism, lipid peroxidation and antioxidant enzymes activity in rat liver tissues under acute hypoxia (AH). Six groups of Wistar male rats participated in the study. Animals of Gr. I underwent i.p. saline injection, Gr. II--saline injection and AH (inhalation of 7% O2, 30 min). Gr. III and IY were examined after i.p. injection of SC (50 mg/kg) or KGL (200 mg/kg) and AH test; Gr. Y-after i.p. injection of SC with alpha- beta-adrenoblockers phentolamine and obzidane (2 mg each) and AH test, Gr. 6-after i.p. injection of KGL with M- and N-cholinoreceptor blockers athropine (5 mg) and benzohexonium (10 mg) and AH test. It was shown that AH provoked the decrease of NO production by 34%, the addition of SC augmented twice the nitrite anion content, the addition of KGL--in three times. KGL decreased malon dialdehyde content under AH by 32% and SC- by 25%. The least level of lipid peroxidation was registered in Gr. YI. Adrenoblockers did not influence on antioxidant enzymes activity under AH, but cholinoblockers completely eliminated the increase of SOD, catalase, glutathione peroxidase and glutathione reductase activities under KGL treatment. We conclude that nitric oxide production under alpha-ketoglutarate influence is mediated by cholinoreceptors.

[NO-dependent effects during adaptation of rats to intermittent hypoxia]. / NO-zalezhni efekty adaptatsiï shchuriv do hipoksiï v interval'nomu rezhymi.

In experiments on Wistar rats processes nitric oxide production on concentration of anions (NO2-, NO3-), carbamide and polyamines contents were investigated in processes of rats adaptation to acute hypoxia (7% O2 in N2, 30 min) and intermittent hypoxia training (10% O2 in N2, 15 min, 5 cycles daily) during 14 days. NO production by oxygen-dependent and oxygen-independent metabolites paths has been investigated. It is concluded that the disturbances in nitric oxide system induced by acute hypoxia by L-arginine injections may result in acute hypoxia.

[Effect of ATP-sensitive potassium channel modulators and intermittent hypoxia on mitochondrial respiration during stress]. / Vplyv moduliatoriv ATP-chutlyvykh kaliievykh kanaliv ta interval'noho hipoksychnoho trenuvannia na mitokhondrial'ne dykhannia za stresu.

The influence of activator of ATP-sensitive potassium channels (KATP) pinacidil and blocker glibenclamide after intermittent hypoxia in rats under stress condition on ADP-stimulated mitochondrial respiration by Chance and lipid peroxidation processes in liver have been investigated. We used next substrates of oxidation--0.35 mM succinate, 1 mM alpha-ketoglutarate, 3 mM glutamate, 3 mM pyruvate, 2.5 mM malate and inhibitor of the mitochondrial fermentative complex I (10 microM rotenone), succinate dehydrogenase inhibitor (2 mM malonate) and inhibitor of transamination (1 mM aminooxiacetate). We suggest that adaptation by intermittent hypoxia and application of a KATP opener pinacidil possess significant protective effect on mitochondrial energy support under stress condition. Combination of intermittent hypoxia with pinacidil causes more efficient consumption of oxygen and decrease of lipid peroxidation processes comparative to intermittent hypoxia or pinacidil injection used separately. We conclude about the existence of the functional link between nitric oxide which is being increased under intermittent hypoxia and KATP opener. Both intermittent hypoxia and pinacidil effectively decrease the negative results of mitochondrial dysfunction under stress condition.

[Exogenous L-arginine modulates mitochondrial and microsomal oxidation in acute and intermittent normobaric hypoxia]. / Moduliatsiia ekzohennym L-arhininom mitokhondrial'noho ta mikrosomal'noho okysnennia pry hostrii ta periodychnii normobarychnii hipoksiï.

It is known that protective effects of adaptation to intermittent hypoxia are mediated partly by stimulating of some mitochondrial and microsomal enzymes activity. Our objective was to investigate whether exogenous NO (L-arginine) or NO blocker (L-NNA) modulate mitochondrial and microsomal oxidation during acute hypoxia (AH) and intermittent hypoxic training (IHT). In control rats AH (inhalation of 7% O2, 30 min) provoked a decrease of ADP-stimulated liver mitochondrial respiration. However, the pattern of oxidation substrates was different from normoxic controls. In the presence of succinate, an increase of the Chance respiratory coefficient and the phosphorylation rate and a decrease of O2 uptake efficacy with simultaneous activation of aspartate aminotransferase activity were observed. Simultaneously, oxidation of a-ketoglutarate, an NAD-dependent substrate, was inhibited. IHT caused reorganization of mitochondrial energy metabolism favoring NAD-dependent oxidation and improving the protection against acute hypoxia. After 14 days of normobaric IHT (10% O2, 15-min sessions with 15 min rest intervals, 5 times daily), in comparison to controls acute hypoxic challenge in the presence of succinate resulted in an increase of the Chance respiratory coefficient, the ADP/O ratio and the phosphorylation rate, in activation of both aspartate and alanine aminotranferases, and in less lipid peroxidation. The microsomal oxidation was not changed under AH per se but significantly decreased (by 37%) during acute hypoxic test after ITH. These findings indicated a more efficient use of oxygen under hypoxic conditions after IHT pre-conditioning. The combination of IHT with L-arginine treatment (600 mg/kg intraperitoneally, daily before IHT sessions) provoked more pronounced decrease of tissue oxygen consumption and microsomal oxidative processes in comparison with IHT animals. L-arginine effects were abolished by the NO-synthase blocker L-NNA. We conclude that the combination of IHT with NO-donor treatment provokes a decrease in aerobic link of energy regulation thereby increasing the tolerance to episodes of acute hypoxia.

[Intermittent hypoxic training and L-arginine as corrective agents for myocardial energy supply under acute hypoxia]. / Interval'ni hipoksychni trenuvannia ta L-arhinin iak zasoby korektsiï enerhozabezpechennia miokarda za umov hostroï hipoksiï.

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.

[Regulation of oxidative phosphorylation by liver mitochondria receptors after adaptation by rats to periodic normal pressure and acute hypoxia]. / Retseptorna rehuliatsiia okysliuval'noho fosforyluvannia mitokhondrii pechinky za adaptatsiï shchuriv do periodychnoï normobarychnoï i hostroï hipoksiï.

It is known that NO-dependent mechanisms are involved in mitochondrial adaptive reactions to different factors. The object of this study was to investigate the role of cholino- and adrenoreceptors in NO-dependent reactions of rat liver mitochondria to acute hypoxia (AH) and intermittent hypoxic training (IHT). Eight groups of Wistar male rats participated in the study. Animals of Gr. I underwent daily i.p. saline injections during 14 days. Gr. II was examined after a single AH test (inhalation of 7% O2, 30 min) with the same saline treatment. Another six groups were exposed to IHT (11% O2, 15-min sessions with 15 min rest intervals, 5 times daily during 14-days), at that 15 min before every IHT session animals underwent i.p. treatment: Gr. III and IV--saline, Gr. V--L-arginine, Gr. VI--NO synthase blocker L-NNA, Gr. VII--L-arginine with alpha-, beta-adrenoblockers phentolamine and obzidane, Gr. VIII--L-arginine with M- and N-cholinoreceptor blockers athropine and benzohexonium. After IHT Gr. IV-VIII were exposed to a single AH test and decapitated just after that. In control rats AH provoked: 1) in the presence of succinate, a 33% augmentation of ADP-stimulated mitochondrial respiration (V3) with a 18% decrease of O2 uptake efficiency (ADP/O ratio); 2) in the presence of alpha-ketoglutarate, a NAD-dependent substrate, no changes in V3 were observed, also 21% augmentation of ADP/O ratio registered. These events were accompanied by 36% increase in succinate dehydrogenase (SDG) activity, two-fold augmentation of malon dialdehyde (MDA) content and 43% increase in diene conjugates (DK). IHT caused reorganization of mitochondrial energy metabolism improving the protection against acute hypoxia. A decrease by 40% in activation of mitochondrial respiration in the presence of succinate (V3--by 40% and V4--by 34%), a reduction of MDA and DK content (by 32% and 20%, respectively), an increase in SGD activity by 31% was observed in Gr. IY compared to Gr. II. Extra exogenous NO (Gr.Y) did not influence V3 and V4 in the presence of succinate, but in the presence of alpha-ketoglutarate decreased them by 9% and 29%, respectively, as well as ADP/O ratio by 28% on the background of SDG inhibition by 24% and the decrease of MDA content by 34%, that is reduced aerobic energy supply and reactive oxygen species production. L-arginine effects were abolished by L-NNA. Effects of cholinoreceptor blockers over L-arginine (Gr. VIII) resembled effects of AH: considerable activation of succinate and alpha-ketoglutarate oxidation in stage V3 by 44% and 75%, respectively, was observed which was accompanied by a decrease in ADP/O by 21% and 31%, and V3/V4 by 15% and 28%, respectively, in comparison to Gr.Y. It indicates that effects of L-arginine are mediated mainly by cholinoreceptors. The effects of adrenoreceptors blockade strengthened the combined effects of IHT with L-arginine treatment, confirming primary role of cholinoreceptors in NO-dependent mitochondrial reactions to IHT. Thus, oxygen uptake and its effective usage depend on dynamic status of adreno- and cholinoreceptors. We conclude that protective effects of the combination of IHT with NO-donor treatment under acute hypoxia are mainly realized through cholinoreceptors.

[Effect of tricarboxylic acid cycle intermediates on nitric oxide system during acute hypoxia]. / Vplyv intermediativ tsyklu trikarbonovykh kyslot na systemu oksydu azotu za hostroï hipoksiï orhanizmu.

Effects Crebs Cycle of exogenous intermediates sodium succinate (50 mg/kg) and sodium alpha-ketoglutarate (200 mg/kg) on processes of mitochondrial ADP-stimulated respiration (using as substrates of oxidation 0.35 mM succinate, 1 mM alpha-ketoglutarate), production of nitric oxide under NO2-, NO3-, as well as carbamide, putrescyne content and processes of lipid peroxidation in the rats liver under acute hypoxia (7% O2 in N2, 30 min) have been studied. It was shown, that the exogenous sodium alpha-ketoglutarate increases nitric oxide content, aminotransferase activation, inhibition of succinatedehydrogenase simultaneously more than exogenous sodium succinate. It correlates with decreasing of processes lipid peroxidation in liver.

[State of mitochondrial respiration and calcium capacity in livers of rats with different resistance to hypoxia after injections of L-arginine]. / Stan mitokhondrial'noho dykhannia i kal'tsiievoï iemnosti pechinky shchuriv z riznoiu rezystentnistiu do hipoksiï za umov vvedennia L-arhininu.

In experiments on rats with different resistance to hypoxia are investigated processes of mitochondrial respiration, oxidative phosphorylation and calcium capacity in liver under precursor nitric oxide L-arginine (600 mg/kg) and blockator nitric oxide synthase L-NNA (35 mg/kg) injections. We are used next substrates of oxidation: 0.35 mM succinate, 1 mM alpha-ketoglutarate, 1 mM alpha-ketoglutarate and 2 mM malonic acid. Increasing of ADP-stimulation respiration states under exogenous L-arginine injection, decreasing efficacy of respiration processes (respiration control on Chance and ADP/O) under such substrates oxidation, testify to oxide energy support decreasing and reversing nitric oxide inhibit in such conditions. This will be used as mechanism cell regulation succinate dehydrogenase activity. It has shown that L-arginine injection increase calcium mitochondrial capacity low resistance to hypoxia rats using substrates of oxidation succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of nitric oxide precursor influence on this processes limit NO-synthase inhibitor L-NNA.

[Effect of nitric oxide synthase inhibitor L-NNA on the activities of antioxidant enzymes and lipid peroxidation in blood and tissues of rats with different resistance to hypoxia]. / Vplyv modyfikatsiï produktsiï oksydu azotu L-NNA na stan systemy antyoksydantnoho zakhystu i perekysnoho okysnennia lipidiv u krovi ta tkanynakh shchuriv z piznoiu pezystentnistiu do hipoksiï.

The main components of antioxidant enzyme system (AOS) are superoxide dismutase (SOD) and glutathione reductase (GR) catalyses the conversion of the superoxide anion. The important role in AOS belongs to catalase and glutathione peroxidase which perform H2O2 to nontoxic products. Simultaneous determination of AOS activity and malonic dialdehide (MDA) concentration (the index of lipid peroxidation in tissues and blood) characterize cells complex resistance to damage factor. The effect of L-arginine, as a precursor of nitric oxide synthesis and blocator NO-synthase (Nw-nitro-L-arginine) on AOS of rats with different resistance to hypoxia under stress condition is unknown and were subject of our investigation. Experiments were done on liver and blood tissues of white laboratory rats. The experimental animals were divided on two groups depending on hypoxia factor: high resistance (HR) and low resistance (LR). The type of resistance was determined by the time of ability to respire in barocamera with oxygen deficient equal to 12.000 meters over sea level. The animals adaptation to laboratory conditions continue during 14 days after in barocamera presence. All animals were divided dependent on experiment conditions on fourth groups. The first group: intact (HR and LR) animals parentherally injected by 1 ml of 0.9% NaCl solution. The second group was subject of stress condition. The third group: HR and LR animals injected parentherally by 1 ml L-arginine (Sigma, USA) dose (600 mg/kg body weight). The fourth one: rats injected by 1 ml Nw-nitro-L-arginine (L-NNA, Sigma, USA)--the blocator of NO-synthase. The animals were decapitated 30 min after injection and stress condition under ethereal anesthesia. Activity of antioxidant system enzymes superoxide dismutase (SOD), catalase (CAT); glutathione reductase (GR), glutathione peroxidase (GP) were measured spectrophotometrically. Also was investigated the concentration of serum antioxidant ceruloplasmin (CP). Level of lipid peroxidation was estimate by examination of concentration of lipids of hydroperoxides (LHP) and malonic dialdehyde (MDA). Our data confirm suggesting that nitric oxide (NO) is a major regulator in the AOS enzymes activity and limit damage influence of AOF. Action precursor NO L-arginine might be capable of protective role in various disorders which are connected with hypoxia factor. Following thing can be interred the investigation of influence of nitric oxide adaptive answers in stress condition modelling of pathological processes in rats with different resistance to hypoxia and reflect the biological qualities data stady on AOZ and LP.

[Effect of L-arginine and N(omega)-nitro-L-arginine on oxidative phosphorylation and lipid peroxidation in rats with various tolerance to hypoxia under stressful conditions]. / Vplyv L-arhininu ta N(omega)-nitro-L-arhininu na okysne fosforylovannia i protsesy lipoperoksydatsiï u shchuriv z riznoiu rezystentnistiu do hipoksiï za umov stresu.

The influence of L-arginine (600 mg/kg) and NO-synthase blocator N omega-nitro-L-arginine L-NNA (35 mg/kg) on processes of ADP-stimulated respiration (under using 0.35 mM succinate, 1 mM alpha-ketoglutarate, 2 mM pyruvate, 2 mM glutamate, 2 Mm malate and succinate dehydrohenase blocator--2 mM malonate as substrates of oxidation), lipid peroxidation (concentration of DK and MDA), activities of succinate dehydrohenase and aminotransferases in rats tissues with different resistance to hypoxia under stress conditions have been investigated. It have been shown that the energy metabolism indices (respiration rate and efficiency of phosphorilation ADP/O) are higher in high resistent (HR) animals in the control group. Stress causes the increase of ADP-stimulated respiration in low resistent (LR) under succinate oxidation and decrease of NADPH-dependent utilization, indicative of more effort of energy system in LR animals. Stress conditions are connected with the increase of lipid peroxidation products in blood both in LR and in HR animals, though in hepar their concentration change unimportantly. Injection of L-arginine decreases aerobic component of energy metabolism on the background decreasing aminotransferases ways of oxidation and succinate dehydrohenase activity. L-arginine causes decrease of lipid peroxidation products in LR, in HR the same effect reaches by L-NNA injection. The has been made conclusion about tight correlation between energy metabolism, processes of lipid peroxidation with resistance to hypoxia and functioning of nitric oxide cycle under stress conditions.

[Effect of L-arginine and the nitric oxide synthase blocker L-NNA on calcium capacity in rat liver mitochondria with differing resistance to hypoxia]. / Vplyv L-arhininu i blokatora syntazy oksydu azotu L-NNA na kal'tsiievu iemnist' mitokhondrii pechinky shchuriv z riznoiu rezystentnistiu do hipoksiï.

The effect of L-arginine and blockator of nitric oxide synthase L-NNA on processes of calcium mitochondrial capacity in liver with different resistance to hypoxia in the experiments with Wistar rats has been studied using the followrng substrates of energy support: succinic, alpha-ketoglutaric acids, alpha-ketolutarate and inhibitor succinatedehydrogenase malonate. As well we used substrates mixtures combination providing for activation of aminotransferase mechanism: glutamate and piruvate, glutamate and malate. It has been shown that L-arginine injection increases calcium mitochondrial capacity of low resistant rats using as substrates the succinate and alpha-ketoglutarate to control meanings of high resistance rats. Effects of donors nitric oxide on this processes limit NO-synthase inhibitor L-NNA.

[The effect of sodium alpha-ketoglutarate on the indices of the peripheral blood and lipid peroxidation and on the enzyme activity of antioxidant protection in irradiated rats]. / Vplyv al'fa-ketohlutaratu natriiu na pokaznyky peryferychnoi krovi, perekysnoho okysnennia lipidiv i aktyvnist' fermentiv antyoksydantnoho zakhystu oprominenykh shchuriv.

The influence of chronic roentgen irradiation in low doses on rats' quantitative and qualitative indices of peripheral blood, on lipid peroxidation and on erythrocyte antioxidant enzymes activity has been studied. It was shown that chronic roentgen irradiation in low doses had a destabilizing influence on leucocytes correlation, activated lipid peroxidation, depressed activity of erythrocytes antioxidant enzymes. Alpha-ketoglutarate injection in therapeutic doses normalized blood indices, limited the intensity of lipid peroxidation and activated antioxidant system enzymes.

[The effect of sodium alpha-ketoglutarate on the physical load endurance of rats with different resistances to hypoxia]. / Vplyv al'fa-ketohlutaratu natriiu na vytryvalist' do fizychnoho navantazhennia u shchuriv z riznoiu rezystentnist' do hipoksiï.

The studies have been performed in high- (HR) and low-resistant (LR) to hypoxia animals swimming to the point of exhaustion. It has been established that HR rats are capable to endure the dynamic load twice longer. The introduction of sodium alpha-ketoglutarate (SKG) increases the endurance of LR animals to the level of the HR ones, activates the aminotransferase mechanisms of ketoglutarate utilization and decreased tissue succinic dehydrogenase activity. SKG injection activates the cholinergic link of regulation in this conditions. Such functional reorganization in a body is directed to decreasing the energy expenses in HR and LR animals under relevant significant functional loads and restriction of the influence of lipid peroxidation products (determined by blood and tissue concentration of malonic dialdehyde) to cellular membrane.

[The effect of the parenteral administration of alpha-ketoglutarate on the resistance of rats to ionizing radiation and on their cholinergic systems]. / Vplyv parenteral'noho vvedennia al'fa-ketohlutaratu na rezystentnist' shchuriv do ionizuiuchoho oprominennia ta kholinerhichnu systemu ïkh orhanizmu.

We have investigate the effect of sodium ketoglutarate intraperitoneal injection (20 mg/100 g body weight) made 0.5 hour before and 1, 2 and 3 hours after total X-ray treatment (259 mKl/kg) on the survival of rats. Simultaneously we have define changes in cholinesterase-acetylcholine system and content of adrenaline and noradrenaline in liver and pancreas tissues, small intestines mucous and in blood. All the data were taking at 1, 2, 5, 4, 24 and 72 hours after treatment and sodium ketoglutarate injection. We have found that sodium ketoglutarate injection made 0.5 hour before the treatment results in increasing of percentage death rate and injection made 1 and 2 hours after treatment results in increase in survival of rats. The effect of alpha-ketoglutarate injection made 1 hour after treatment in more pronounced. It is accompanied with increase of cholinergic status of organism on the catecholamine deficit background, decrease in the cholinesterase activity and increase of acetylcholine content in tissues of treated organism.

[The effect of sodium alpha-glutarate on enzymatic transamination activity and on succinate dehydrogenase in rats with different resistances to hypoxia]. / Vplyv al'fa-ketohlutaratu natriiu na aktyvnist' fermentiv pereaminuvannia ta suktsynatdehidrohenazy u shchuriv z riznoiu rezystentnistiu do hipoksiï.

It have been found that intraperitoneal alpha-ketoglutarate injection (20 mg/100 g body weight) results in increase in the influence of cholinergic regulation mechanisms. It also results in increase of aminotransferase activity on background of the decrease of succinate dehydrogenase activity in liver and pancreas tissues and in small intestines mucous. Activity of transamination enzymes and succinate dehydrogenase activity is much higher in the case of rats with high hypoxia resistance, alpha-ketoglutarate injection results in increase of transamination enzymes activity in the organisms of rats with low resistance to hypoxia up to the control level of rats with high resistance, and simultaneously increases rats resistance to hypoxia. Effect of alpha-ketoglutarate injection on the energetical exchange in the tissues with different parasympathetic dependence taking from the animals with different hypoxia resistance is suppressed by blockade of M- and H-cholinoceptors.