Effect of preliminary adaptation to short-term stress exposure on the resistance of the spontaneously contracting myocardium to a lipid peroxidation inducer

Contractile function of the isolated right atrium was studied in male Wistar rats adapted to short-term stressor exposures at varying times after adaptation was completed. Adaptation to short-term stressor exposures induced a limited decrease in myocardial contractility immediately after adaptation was over. On the 3d day an additional reduction in the characteristics of contractile function was still observed. However, by the 5th day the characteristics recovered to the control level. At the same time adaptation completely prevented the derangement of myocardial contractility, induced by exposure to a prolonged stress. That protective effect was observed as early as adaptation was completed, on days 3 and 5 after adaptation, and became lessened on the 10th day. It is assumed that on the 5th day after adaptation the animals are in a postadaptation state where the untoward effect of adaptation disappears whereas the protective effect is demonstrable to a full extent. As a result all the characteristics of myocardial contractility following a prolonged stress on the 5th day after completion of short-term stressor exposures differed in no way from the control parameters.     

Increased enzymatic activity of antioxidant protection of the heart in the adaptation of rats to short-term stress exposure

It has been shown that adaptation to short-term emotional-painful stresses leads to an increase in antioxidant enzyme activities but does not change vitamin E content in the myocardium. The most labile enzyme was catalase (35% increase). During stress in nonadapted animals the enzyme activity decreased, as compared to the control, while in the group of adapted animals with subsequent stress the activity was even higher than in the control. During initiation of lipid peroxidation in the heart homogenates in vitro there was a 3-fold increase and a 1%-fold decrease in the oxidation intensity in rats exposed to stress and in adapted animals, respectively. The role of adaptation activation of cardiac antioxidant system in the prevention of stress-induced heart damage is discussed.     

Myocardial contraction in the reverse development of adaptation to short-term exposure to stress

Contractile function of an isolated right atrium was studied in short-term stressor effects-adapted male Wistar rats at different times after adaptation was completed. Adaptation to short-term stressor effects was shown to produce a restricted decrease of myocardial contractility shortly after adaptation was completed. At the 3d day another decrease of contractile function was noted. However, contractile function returned to the control level by the 5th day. At the same time adaptation completely prevented the impairment of myocardial contractility, induced by prolonged stress. The protective effect was seen immediately after adaptation, by days 3 and 5 after it, being reduced by day 10. It is assumed that at the 5th day after adaptation, the animals experience the post-adaptation state marked by disappearance of the negative adaptation effect and by remarkable protective effect of adaptation. As a result, all the characteristics of myocardial contractility evaluated after prolonged stress experienced by the animals at the 5th day following short-term stressor effects do not differ from control parameters.     

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 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.     

Catalase activity in the myocardium during stress in adult and aged rats]

The study of catalase myocardium activity at stress in adult and old rats has been performed. It has been revealed that the formation of immobilization stress is accompanied by the enzyme activity stimulation. The expression of this effects is more significant in adult animals. Experimental data concerning the possible role of peroxidation lipids in myocardium catalase stress activation and its age modulation are given.     

Prevention of stress-induced disorders of myocardial contractile function by using sparing adaptation to short-term stress effects

Adaptation to repeated short-term stress is known to prevent to a considerable extent the depression of the myocardial contractile function which usually develops under long-term stress. But the adaptation itself has a "cost", i. e. it results in limited but significant disturbances of myocardial contractile function. The present review documents the method of adaptation involving few actions with prolonged intervals between them. It has been established that such an adaptation per se does not induce any disturbances of contractile function. At the same time it prevents completely the depression of contractile function caused by stress.     

Changes in fibrinolysis components during short-term adaptation to high altitude]

In studying hemocoagulation in dogs under conditions of Frunze (760 m above the sea level) and Tuya-Ashu (3200 m above the sea level) it was shown that in the "emergency" phase of adaptation (the first three days) there was seen activation of fibrinolysin and profibrinolysin with depression of antifibrinolysins and inhibitors of profibrinolysin activators. The concentration of plasma fibrinogen at that period decreased by 100 mg%, which could promote an increase in the vascular permeability and improvement of oxygen approach to the tissues. Later, along with elevation of fibrinolysin and profibrinolysin activators there was a marked increase in the level of fibrinolysis inhibitors. Correlation of all the fibrinolysis components was established at a new level.     

Structural changes in the rat myocardium in the process of adaptation to high-altitude hypoxia]

Changes in the weight of diverse parts of the heart, in cross-sectional area of myocytes and vascularization of the myocardium were studied in rat experiments under altitude hypoxia (3200 m above the sea level) during adaptation of the animals to hypoxia. Morphologically, the compensatory and adaptive reactions of the rat to hypoxia were shown by its increases weight at the expense of hypertrophy of the right ventricular myocardium. Vascularization of the myocardium augmented synchronously to its growing hypertrophy.     

Effect of adaptation to short-term stress exposure on the fibrillation threshold and ectopic activity of the heart in experimental myocardial infarct

Preliminary adaptation to short-term stress was shown to prevent the decrease in the heart fibrillation threshold and an increase in ectopic activity which is usually observed in experimental myocardial infarction. This protective effect involves an enhanced activity of the antioxidant system. Therefore, a synthetic antioxidant ionol was applied to prevent disturbances of the heart electrical stability in infarction. It was established that ionol completely prevents the decrease in the electrical threshold and the increase in ectopic activity of the heart in experimental infarction. Thus, it can be concluded that ionol possesses an antiarrhythmic effect.     

Effects of adaptation to exposure to short-term stress on indices of resistance of energy metabolism and contractile function of the myocardium to acute hypoxic hypoxia and reoxygenation

Effect of preliminary adaptation to immobilization stress with progressive duration from 15 min. to 1 h (every second day, 8 sessions) on the resistance of indices of myocardial energy metabolism and contractile function to acute hypoxic hypoxia and subsequent reoxygenation was studied. It was shown, that adaptation to short-term stress exposure by some way provided the retention of activities of important enzymes like creatine-phosphokinase and phosphorylase under the harmful action of acute hypoxia and subsequent reoxygenation. At the same time, the ATP restoration and the CP super-restoration were observed during reoxygenation. This effect, in its turn, was accompanied by a more pronounced super-restoration of the heart contractile function than in control.     

Diacylglycerol effects on phosphatidylinositol-specific phospholipase C activity and vesicle fusion

Diacylglycerol increased the hydrolytic activity of phosphatidylinositol-specific phospholipase C on large unilamellar vesicles containing 5-40% phosphatidylinositol. Moreover, diacylglycerol increased the rate and extent of vesicle fusion (contents mixing) induced by the enzyme. Kinetic studies of intervesicular lipid mixing revealed that fusion was limited by the frequency of contacts involving two diacylglycerol-rich domains.     

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.     

Alpha1 desensitization of the heart during adaptation to stress]

Results of the experiments evidence that a combination of three factors, limiting the Ca2+ concentration increase in myocardial cell, can play a role in the cardioprotective effect of adaptation of rats to short-term immobilization stress (every second day for a month) are presented. Those factors are as follows: desensitization of alpha 1-adrenoreceptors, M-cholinoreceptors up-regulation and reduced number of voltage-dependent Ca2+ channels in the myocardial membranes.     

Prevention of cardiac contractile function disorders during prolonged stress by preliminary adaptation to short-term stress exposure

Studies of contractile function of an isolated right auricle in Wistar rats have demonstrated that long-term immobilization stress (fixation in the lying position for 6 h) results in the decreased extensibility of the auricle and pronounced depression of the developed tension. Preliminary adaptation of the animals to short-term immobilization stress (daily fixation in the lying position for 1 h over 10 days) per se insignificantly affects the extensibility and contractile function of the auricle but in effect it reduces its adrenoreactivity and completely prevents the post-stressor rigidity of the auricle and its function abnormality after long-term stress.     

Regulation of nuclear phospholipase C activity

A body of evidence, linking inositide-specific phospholipase C (PI-PLC) to the nucleus, is quite extensive. The main isoform in the nucleus is PI-PLCbeta1, whose activity is up-regulated in response to insulin-like growth factor-1 (IGF-1) or insulin stimulation. Whilst at the plasma membrane this PI-PLC is activated and regulated by Galphaq/alpha(11) and Gbetagamma subunits, there is yet no evidence that qalpha/alpha(11) is present within the nuclear compartment, neither GTP-gamma-S nor AlF4 can stimulate PI-PLCbeta1 activity in isolated nuclei. Here we review the evidence that upon occupancy of type 1 IGF receptor there is translocation to the nucleus of phosphorylated mitogen-activated protein kinase (MAPK) which phosphorylates nuclear PI-PLCbeta1 and triggers its signalling, hinting at a separate pathway of regulation depending on the subcellular location of PI-PLCbeta1. The difference in the regulation of the activity of PI-PLCbeta1mirrors the evidence that nuclear and cytoplasmatic inositides can differ markedly in their signalling capability. Indeed, we do know that agonists which affect nuclear inositol lipid cycle at the nucleus do not stimulate the one at the plasma membrane.