Does the Operation of Mitochondrial ATP-Dependent Potassium Channels Affect the Structural Component of Mitochondrial and Endothelial Dysfunctions in Experimental Parkinsonism?

We have previously demonstrated that the development of oxidative stress in some pathologies can be prevented by activation of the mitochondrial ATP-dependent potassium channel (mitoKATP). Here we studied the effect of modulation of mitoKATP on the development of mitochondrial and endothelial dysfunction in the medulla oblongata and myocardium of rats with experimental parkinsonism. It is known that uridine-5'-diphosphate, activator of mitoKATP, does not penetrate the plasma membrane, but it can be synthesized in cells from exogenous uridine that is delivered into cells by special transport systems. Our results suggest that mitoKATP is involved in the development of mitochondrial and endothelial dysfunction in experimental parkinsonism and prove the cardio- and neuroprotective effects of uridine.

Dynamic Restructuring of the Myocardial Mitochondria in Response to Uridine Modulation of the Activity of Mitochondrial ATP-Dependent Potassium Channel under Conditions of Acute Hypoxic Hypoxia.

We studied the effects of in vivo modulation of activity of mitochondrial ATP-dependent potassium channel (mitoKATP) by uridine on the morphofunctional state of mitochondria in rat cardiomyocytes under conditions of acute hypoxia. Preinjection of uridine to animals reduced the number of structurally modified mitochondria, but had practically no effect on their morphogenesis after hypoxia. Uridine in vivo stimulated the formation of micromitochondria and their release into the cytoplasm. The number of "maternal" mitochondria containing three and more new micromitochondria, increased as well. The use of mitoKATP blocker 5-hydroxydecanoate in parallel with uridine abolished its protective effect, as it significantly inhibited the formation of micromitochondria in rat cardiomyocytes after acute hypoxic exposure.

Structural and Dynamic Changes in Mitochondria of Rat Myocardium under Acute Hypoxic Hypoxia: Role of Mitochondrial ATP-Dependent Potassium Channel.

The ultrastructure and spatial localization of mitochondria (MC) in the myocardium of rats exposed to a 30-min hypoxic hypoxia were investigated. The mitochondrial structure was found to undergo changes; however, marked necrotic injuries were not observed. Changes occurring in the myocardium are aimed at the intensification of energy processes. This shows up as an increase in the number of MC in the subsarcolemmal zone of the myocardium and changes in the surface of the sublemmal membrane due to its bending around mitochondria, which improves the diffusion of oxygen into MC. In addition, the division of MC is enhanced, which partially explains the increase in their total number. In structurally altered MC with intact membrane, electron dense formations with small diameter appear, which probably represent newly formed organelles (microMC). In normoxia, changes of this kind do not occur. It was found that the ATP-dependent K+ channel is involved in the regulation of the morphological state of MC under hypoxic hypoxia. The activator of the channel diazoxide increases the number of newly formed microMC, and the channel inhibitor 5HD significantly prevents their formation. Possible mechanisms of structural and dynamic changes in rat myocardial MC under acute hypoxic hypoxia are discussed.

Effects of different modes of interval hypoxic training on morphological characteristics and antioxidant status of heart and lung tissues.

The effects of various modes of interval hypoxic training differing by the intensity and duration of hypoxic exposure on the morphology and antioxidant status of the heart and lung tissues were studied. Interval hypoxic training mode with more severe, but shorter hypoxic component led to the prooxidant/antioxidant imbalance in the myocardial and lung tissues, which was paralleled by significant disorders in their morphology and function. Moderate hypoxic exposure of different duration promoted the maintenance of optimum antioxidant homeostasis and development of compensatory adaptive changes in tissue structure.

[The physiological role of the structural-functional changes in the air-blood barrier of the lungs in supplying the body with oxygen under the action of extreme factors]. / O fiziologicheskoi roli strukturno-funktsional'nykh izmenenii aérogematicheskogo bar'era legkikh v obespechenii organizma kislorodom pri deistvii ékstremal'nykh faktorov.

Hypoxic states, under the effect of extreme factors, induced changes in the endothelium of the lung capillaries irrespective of the nature of the factors (exo- or endogenous) causing the hypoxic state. Significant changes of the mitochondrial apparatus of the lung air-blood barrier cells occurred in the hypoxic hypoxia. The data obtained suggest that the thickness of the ABB, under extreme conditions, cannot serve as a parameter of the morphofunctional state of the lung ABB. The compensatory-adaptive response of the cell structures seem to decrease the oxygen diffusion from the alveolar gas into the blood of the lung capillaries.

[The morphofunctional characteristics of the pulmonary air-blood barrier in rats breathing gas mixtures with a high content of hydrogen sulfide]. / Morfofunktsional'naia kharakteristika aérogematicheskogo bar'era legkikh u krys pri dykhanii gazovymi smesiami s vysokim soderzhaniem serovodoroda.

The influence of gas mixtures with high concentration of pure hydrogen sulphide and natural gas of the Astrakhan deposit (NGAD) upon the morphofunctional state of the aerohematic barrier (AHB) and the surfactant system of the lungs was studied in 80 albino Wistar rats of 180-250 g body weight. The influence of both hydrogen sulphide and NGAD results in the appearance of morphofunctional alterations in the AHB and surfactant system of the lungs. However, if the action of hydrogen sulphide in concentrations of 300-330 and 600-700 mg/m3 is followed not only by pathological manifestations but also by mobilization of certain compensatory-adaptational mechanisms such as reinforcement of pinocytosis, the action of NGAD with the similar concentration of hydrogen sulphide seems to be too toxic, surpassing the possibilities of compensation, and there occurs the development of purely pathological phenomenon--pulmonary edema.

[Effect of the antihypoxic agent ionol on the morphofunctional state of the air-blood barrier of the lungs in hypoxic anoxia]. / Vliianie antigipoksanta ionola na morfofunktsional'noe sostoianie aérogematicheskogo bar'era legkikh pri gipoksicheskoi.

It is shown that antihypoxic ionol has promoted normalization of the air-blood lung barrier ultrastructure, activation of the surfactant system under acute hypoxic hypoxia effect as well as compensatory redistribution of the thickness of separate barrier layers due to intensified synthesis of phospholipids which are the components of cytoplasmic membranes and pulmonary surfactant.

[The electron microscopic characteristics of stress lung]. / Elektronno-mikroskopicheskaia kharakteristika stressornogo legkogo.

The influence of long-term (6 hours) immobilization stress on morphofunctional state of lung air-blood barrier was studied in experiments of the rats. It was shown that stress provoked the marked ultrastructural changes in the lungs, which were as follows: lung tissue oedema, pronounced thickening of lung air-blood barrier and its separate layers, edema-hemorrhagic syndrome, alveolar epithelial injury, disturbance of lung surfactant systems. Such a pathological complex may be designated as a "stress lung".

[Changes in the blood-air barrier of the lungs in hyperthermia]. / Izmeneniia aérogematicheskogo bar'era legkikh pri gipertermii.

The influence of hyperthermia on the ultrastructure of lung air-blood barrier (ABB) was studied in experiments on dogs. It was shown that in hyperthermia both mean arithmetic and mean harmonic thickness of ABB were increased. The lung capillary endothelial layer was the most thick ABB layer, in which severe micropinocytosis could be observed. Marked destructive changes were noted in lung alveolar epithelial ABB layer up to the appearance of cell content in alveolar space and denudation of the epithelial basal membrane.

[Air-blood barrier of the lungs in acute hypoxic hypoxia as affected by liposomes]. / Aérogematicheskii bar'er legkikh pri ostroi gipoksicheskoi gipoksii pod vliianiem liposom.

Phospholipids injected into the organism under an acute hypoxic hypoxia prevent development of ultrastructural disorders in the air-blood barrier of the lungs, thus averting development of the pulmonary acute hypoxic hypoxia.

[Changes in the air-blood barrier of the lungs during the breathing of helium-oxygen gas mixtures]. / Izmeneniia aérogematicheskogo bar'era legkikh v usloviiakh dykhaniia gelio-kislorodnymi gazovymi smesiami.

The changes in the pulmonary air-blood barrier (ABB), occurring under the influence of helium-oxygen gaseous mixtures containing 11, 21 and 40% O2 in helium were studied in rats of two age groups (adult animals and 2-week-old cubs). The mean arithmetic and harmonic thickness of the ABB increased and its ultrastructure changed. It is suggested that helium exerts an indirect effect on the pulmonary ABB and that this effect does not depend on the O2 concentration in a gaseous mixture or on the animals' age. The electron microscopy data have demonstrated the endothelium of lung capillaries to be the most sensitive structural component as regards the action of helium-oxygen gaseous mixtures.