Prevention of stress dyslipidemia by adapting animals to the periodic action of hypoxia

Emotional-painful stress in rats results in the increase of atherogenic and decrease of antiatherogenic lipoprotein fractions. Adaptation of animals to periodic intermittent hypoxia significantly enhanced the proportion of antiatherogenic lipoproteins in the blood and reduced the degree of post-stress dyslipidemia.     

The effect of adaptation to stress exposures and to periodic hypoxia on the cardiomyocyte trigger activity of the papillary muscles in the rat]

Action potential of cardiomyocytes was recorded in experiments on isolated papillary muscle of the rat left ventricle. The effect was estimated of preliminary adaptation to intermittent hypobaric hypoxia or to short-term stress exposure on the incidence and the pronouncement of delayed after depolarization and of trigger activity induced by a high frequency stimulation against the background of isoproterenol (10(-8) M). It was shown that adaptation to hypoxia or to stress reduced the incidence of delayed after depolarization and of trigger activity, adaptation to stress exerting a more pronounced effect. Immobilization stress (6 hours) potentiated the trigger activity, adaptation to stress exerting a more pronounced effect. Immobilization stress (6 hours) potentiated the trigger activity and this potentiation was effectively prevented by either type of adaptation.     

Effects of adaptation to stress exposure and periodic hypoxia on bioelectric activity of cardiomyocytes of isolated heart in ischemia and reperfusion]

Action potential (AP) of cardiomyocytes was recorded in experiments on isolated perfused according to Langendorf rat hearts. The effect was estimated of preliminary adaptation to intermittent hypobaric hypoxia or to repeated short-term stress exposure on the resting potential (RP) and the amplitude and duration of action potential (APD) in global ischemia and reperfusion. It was shown that adaptation to hypoxia is more effective in prevention of ischemic fall of RP, AP and APD. In reperfusion, the parameters enumerated restored more quickly and efficiently in hearts from adapted to stress animals.     

Effects of adaptation to periodic hypoxia on bioelectric activity of cardiomyocytes of isolated heart in ischemia and reperfusion

Experiments on isolated Wistar rat heart perfused according to Langendorff showed that preliminary adaptation of rats to intermittent hypobaric hypoxia limited the fall of values of the resting potential and the amplitude and duration of action potential characteristic for ischemia. Under similar conditions, adaptation considerably reduced the increased time of impulse conduction along the myocardium. In reperfusion, the parameters enumerated restored much more efficiently in hearts from adapted animals than in controls. The role of these changes in the antiarrhythmic effect of adaptation to intermittent hypoxia is under discussion.     

Effect of adaptation to hypoxia on the antioxidant enzyme activity in the liver in animals that have undergone stress

It was shown in experiments on rats that emotional-painful stress resulted in a rapid increase in malonic dialdehyde (MDA) and in a decrease in the activity of superoxide dismutase (SOD) in liver. Adaptation to moderate intermittent hypoxia in altitude chamber did not affect MDA and increased hepatic SOD by 65%. Stress exposure caused no change in SOD and MDA, but abruptly reduced the fall of SOD in adapted animals. These data are in accordance with the well-known idea that adaptation to hypoxia prevents the activation of lipid peroxidation and the hepatic damage in stress.     

Regulation of oxidative phosphorylation by liver mitochondria receptors after adaptation by rats to periodic normal pressure and acute hypoxia

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.     

Increase of alpha 1-adrenoreactivity of the rat heart in adaptation to periodic hypoxia]

There is a possibility that the cardioprotective effect of adaptation to intermittent hypoxia is due to changes in receptors apparatus of the heart. In this connection the effect of preliminary adaptation to intermittent hypoxia (4 hours per day at the altitude of 4000 m during 40 days) on the state of beta-receptors-adenylate-cyclase system and same other receptors of the heart were studied. It was shown that at the end of the course of adaptation the number of beta-adrenoceptors in the heart was increased with simultaneous decrease in basal adenylate-cyclase activity, accompanied by the diminution of its response to beta-agonist. The number of beta-adrenoceptors was increased by 48% and their affinity to ligand was increased by almost 2 times. The revealed decrease in the reactivity of beta-receptor-adenylate-cyclase system and increase of alpha 1-adrenoreactivity can play a certain role in the mechanism of cardioprotective effect of adaptation to hypoxia.     

Prevention of stress-induced disorders of myocardial Na, K-ATPase activity using adaptation to short-term stress

It was shown that adaptation to short-term emotional-painful stresses prevented both the decline in the activity and the increase in thermal denaturation rate of Na,K-ATPase in sarcolemmal vesicles isolated from the rat myocardium exposed to prolonged stress. The role of Na-pump damage in the disturbance of the electrical stability of the heart and the development of stress-induced arrhythmia is discussed.     

Effect of adaptation to hypoxia on the resistance of rats to the epileptogenic action of penicillin

The influence of adaptation to moderate hypoxia on anticonvulsive resistance of low tolerant rats has been investigated. Focal epilepsy was induced by penicillin application to sensorimotor cortex of the rat brain. Adaptation to hypoxia has been shown to increase the resistance of rats to epileptogenic penicillin effect which is manifested in the prolongation of the latent period of epileptiform discharges and less frequent epileptic fits. The mechanisms of the resistance increase remains to be investigated.     

Participation of heart prostaglandins in cardioprotective cross-effects of adaptation to stress and hypoxia

An adaptation to stress and hypoxia was found to increase the baseline PGE content in the myocardium. The data obtained suggest that the activation of the myocardial system of protective PGs is an important link in the cardioprotective effects of adaptation.     

Natural adaptation to environmental stress via physiological clock-regulation of stress resistance in Drosophila

In the present study we describe a novel mechanism by which populations, in an interplay between physiology and behaviour, can evolve adaptation to environmental extremes. Comparing Drosophila populations from different climate zones, we found diel shifts in high temperature resistance after maintenance at 25 °C for several generations. Resistance changes that co-occurred with field and laboratory activity of the populations are controlled by the physiological clock and appear to be a consequence of local adaptation to the thermal profiles of the environment of origin.     

Prevention of disorders of the electric stability of the heart in experimental infarct using adaptation to hypoxia

It has been shown on rats preadapted to hypoxia in an altitude chamber that myocardial infarction induced by ligation of the coronary artery was accompanied by less disturbances in the electrical stability of the heart, namely by a twofold decrease in ventricular fibrillation threshold and a considerable decrease in the heart ectopic activity. Preliminary adaptation provided the maintenance of myocardial contractility in infarction.     

Effect of adaptation to periodic hypoxia on post-infarction fall of blood pressure and hyperactivation of the endothelium

Acute stress concomitant to the experimental myocardial infarction has induced endothelial hyperactivation of the rat aorta exhibited in an increase of inhibition of norepinephrine-induced contractions of vascular smooth muscle, enhanced endothelium-dependent relaxation correlating with a fall of systemic blood pressure. Preliminary adaptation of rats to intermittent hypobaric hypoxia greatly prevented the stress-induced endothelial hyperactivation and beneficially affected the postinfarction time course of blood pressure.     

Effects of adaptation to periodic and continuous hypoxia in disorders of electrical stability of the heart in postinfarction cardiosclerosis

The effects of adaptation to intermittent and continuous hypoxia on the electrical stability of the heart were compared in middle altitude conditions and in altitude chamber in Wistar rats with postinfarction cardiosclerosis. It has been shown that both forms of adaptation could restore the heart fibrillation threshold and restrict the ectopic activity in postinfarction cardiosclerosis. Beneficial effects of adaptation to intermittent hypoxia in conditions of the altitude chamber appeared to be more radical.