Biomedical subjects

A V Kotsiuruba

Publications and source records attributed to A V Kotsiuruba.

At least 19 recordsLinked to original sources

PubMed2006

[Mechanisms of contractile reaction changes and efficiency of oxygen utilization by portal vein smooth muscles in experimental diabetes mellitus].

On the rat portal vein isolated strips the essential reduction of contractive response, increase of stiffness of vascular smooth muscles at their stretching and increase of oxygen value of smooth muscles' work are revealed in conditions of experimental diabetes mellitus. The possible mechanism of such infringements is chronic hyperglycemia, which results in development of oxidative stress and reduction of NO synthesis by constitutive NOS. Indeed, the significant decrease of activity of constitutive NO-synthase and increase of the oxidative stress markers contents are shown at experimental diabetes mellitus. The similar infringements are marked at in vitro model of hyperglycemia, blockade of NO-synthase and in conditions of oxidative stress. Additional confirmation of a role of NO synthesis blockade and oxidative stress in development of such infringements at diabetes is fact that application of antioxidant melatonin and L-arginine, a precursor of NO to diabetic animals results in partial restoration of contractive reactions, reduction of stiffness and oxygen value of smooth muscles' work.

Animals↗

PubMed2006

[Effect of heme oxygenase-1 expression and activity on the heart function in ischemia-reperfusion].

The purpose of this study was to determine the protective effects of heme oxygenase-1 (HO-1) expression against postischemic myocardial dysfunction. We also investigated HO-1 expression in cardiac tissue from the left and right ventricles of myocardium. Rat hearts were isolated and perfused according to Langendorff technique to evaluate the recovery of myocardial function after 20 min of global ischemia and 40 min of reperfusion. We found that HO-1 expression was more expressed in left ventricles of myocardium in basic conditions and after ischemia/reperfusion as well as after its previous induction by hemin. Upregulation of the inducible isoform of HO-1 and increase its activity after treatment of animals with hemin 24 h before ischemia ameliorated myocardial function (raised left ventricular developed pressure, decreased end-diastolic pressure, attenuated vasoconstriction) and reduced oxydative stress in cardiac tissue during reperfusion of isolated hearts. Zinc protoporphyrin IX, an inhibitor of heme oxygenase activity, completely abolished the HO-1 expression in left ventricles of myocardium and increased postischemic myocardial dysfunction. Likewise, cardiac tissue injury was exacerbated by treatment with zinc protoporphyrin IX through significant inhibition of HO activity and increasing of hydroxyl radical production on reperfusion. The treatment of animals with hemin and following ischemia/reperfusion resulted in 5-6-times increase of HO-1 expression in the left ventricle of myocardium whereas in right ventricle only in 3-times. Our data provide strong evidence for a primary role of HO-1 in cardioprotection against reperfusion injury and show different HO-1 expression in left and right ventricles of myocardium.

Animals↗

PubMed2006

[Melatonin recovers ischemic tolerance and decreases the sensitivity of mitochondrial permeability transition pore opening in the heart of aging rats].

The effect of the hormone of pineal gland melatonin on the ischemic tolerance and the sensitivity of mitochondrial permeability transition pore opening in old rat heart were studied. It has been shown in the Langendorf's isolated rat heart that heart contractile functional changes under ischemia and reperfusion were more pronounced in old (24-27 months) rat hearts in comparison with the adult (5-6 months) animals. A two-week's in vivo course of intraperitoneal injection of melatonin (1,5 mg/kg weight) to old rats contributed to the rehabilitation of the functional changes of isolated heart after ischemia during reperfusion and decreased the sensitivity of mitochondrial permeability transition pore opening to Ca2+ and phenilarsinoxide in comparison with old animals which did not received melatonin. It was accompanied by the significant decreasing in mRNA bax expression in old rat heart, lessening in content of the superoxide radicals and dien conjugates and twice increasing in the activity of constitutive NO-synthase in heart mitochondria of old rat after a course of melatonin injection. The protective feffect of melatonin on the mitochondrial permeability transition pore opening could be used for correction of the cardiac dysfunction with aging.

Aging↗

PubMed2006

[The effects of alpha-linolenic acid on the functioning of the isolated heart during acute myocardial ischemia/reperfusion].

Many studies indicate that dietary omega-3 polyunsaturated fatty acids (PUFAs) have the cardioprotective properties. But majority of experiments were carried out with using omega-3 PUFAs from marine fish oil. The purpose of this study was to determine effects of the plant-derived omega-3 PUFA (alpha-linolenic acid (a-LA) on postischemic myocardial dysfunction, lipid peroxidation and antioxidant enzymes activity. Male Wistar rats (250-300 g) were divided into 4 groups (n = 10-12 each). In control group (1) were intact rats. The hearts from 2-nd group of animal were exposed to 20 min of global ischemia followed by 40 min reperfusion according to the Langendorff technique. The 3-rd and 4-th groups of animal received of the plant-derived oil (a-LA), which is a precursor of eicosapentaenoic acid and was used as a dietary supplement in dose 0.1 mg/kg per day for 4 weeks. The hearts from 4-th group of animal were also exposed to ischemia/ reperfusion. Analysis of myocardial phospholipid fatty acid content showed that consumption of the plant-derived 6-LA for 4 weeks changes fatty acid profile through incorporation of b-LA in cell membranes. It also reduced content of omega-6 PUFAs in membrane phospholipids. In 3-rd group content of a-LA and EPA were increased by 1.5- and 3.5-times, respectively, whereas content of AA was reduced by 1.7-times. The development of ischemia/ reperfusion in 2-nd group caused increase of free AA content in heart tissue by 3.5-times, whereas in 4-th group this increase was only by 1.4-time. Ischemia/reperfusion of the isolated rat heart in 4-th group was accompanied by reduced leukotriene C4 and thromboxane B2 production in 3-times and 1.9-times, respectively in comparison to 2-nd group. The time of myocardial function recovery after ischemia (heart rate, left ventricular development pressure), was shorter compare to 2-nd group. Also in 4th group end-diastolic pressure and coronary perfusion pressure during reperfusion period were significantly lower. Dietary omega-3 PUFAs resulted in remarkable decrease of reperfusion arrhythmias in 4-th group (in 3.8-times) and limited the oxidative stress through decrease free radical and lipid peroxidation production. In this group of animals the activity of antioxidant enzymes (superoxide dismutase and catalase) after ischemia/reperfusion were higher than in 2-nd group. We suggest that dietary supplement of the plant-derived alpha-LA for 4 weeks have cardioprotective effects similar to the effects of fish oil.

Acute Disease↗

PubMed2005

[The effects of omega-3 polyunsaturated fatty acids on lipid peroxidation].

The aim of this study was to evaluate the effects of a diet supplemented with omega-3 polyunsaturated fatty acids (PUFAs) (plant-derived alpha-linolenic acid and eicosapentaenoic and docosahexaenoic acids with alpha-tocopherol (product "Tekom") on the myocardial phospholipid fatty acids composition, lipid peroxidation and activity antioxidant enzymes--superoxide dismutase and catalase in myocardial tissue in control and after ischemia/reperfusion of isolated working rat hearts. Inclusion of omega-3 PUFAs into the animals' diet within 4 weeks demonstrated that alpha-linolenic acid and "Tekom" increased omega-3 polyunsaturated fatty acids content in cardiomyocytes membranes and limited lipid peroxidation (decreased content of congugates of dienes and malone dialdehyde, reduced hemiluminescence of myocardial tissue). Additionally omega-3 PUFAs caused the beneficial effects on activity of antioxidant enzymes in cardiac tissue (increased superoxide dismutase and catalase activity).

Animals↗

PubMed2005

[Effect of L-arginine on the endothelium functional activity in experimental diabetes mellitus].

The experimental data about the shift of L-arginine metabolism in the direction of activization of non-oxidizing (arginase) way under experimental diabetes mellitus are presented. This shift was proved by an increase of the ratio of arginase and NO-synthase activity and an increase of the ratio of their metabolites. The decrease of the free L-arginin contents in tissues of animals with experimental diabetes mellitus is shown. The long infusion of L-arginine results in the restoration of the endothelial function, however cessation of infusion results in a gradual reduction of this effect.

Animals↗

PubMed2005

[Nitric oxide suppresses permeability transition pore opening and enhances calcium uptake in mitochondria in vivo].

The influence of an NO donor, nitroglycerine (NG) on Ca2+ accumulation in rat heart and liver mitochondria was studied. A rapid dose-dependent increase in Ca(2+)-uptake was observed within 5 min after NG injection in vivo, with a peak in NG concentration of 0.5-1.0 mg/kg body weight. There is a correlation between a dose-dependent increase in Ca(2+)-accumulating capacity of mitochondria and sharp dose-dependent rise in stable NO metabolites level (NO2-, NO3- and nitrosothiols) and reactive oxygen species (H2O2 and hydroxyl radical, *OH) as well as lipid oxidation products (diene conjugates), the markers of the oxidative damage of the organelles in mitochondria in comparison to a whole tissue (liver) where only moderate increase of ROS and NO metabolites was detected. A 20-30-fold increase of NO3- level from 32. +/- 2.6 to 736.4 +/- 96.5 nmol/mg protein (p < 0.05) and from 45.4 +/- 6.2 to 1395.0 +/- 121.1 nmol/mg protein (p < 0.05) in liver and heart mitochondria respectively also provide a strong evidence for nitrosative stress. The results obtained suggest that calcium elimination from cytosol and its increased accumulation in mitochondria (likely dependent on permeability transition pore blockade by NO) could account for the cardioprotective action of NG although resulted in the development of oxidative stress with following long-term alterations of the energy supply and metabolism of subcellular structures.

Animals↗

PubMed2005

[Age-related characteristics of contractile vascular reactions and the content of oxygen free radicals and nitric oxide metabolites in BALB/c mice in conditions of alienation zone].

Peculiarities of changes of the endothelium-dependent and endothelium-independent vascular reactions of relaxation, and the content of oxygen free radicals and stable metabolites of nitric oxide (NO) were studied in the aorta preparations of BALB/c mice of the two age groups (6 and 18 months), which were born and lived in the Chernobyl alienation zone. The results obtained showed no endothelium-dependent reactions of aortal smooth muscles relaxation to acetylcholine and only partially impaired endothelium-independent reactions to sodium nitroprusside in animals of both age groups. There was a significant decrease in the content of high-molecular nitrosothiols (HMNT) in old animals, which may signify a depletion of NO depot in the aorta. A decrease of HMNT levels induced an increase of the shares of anion nitrite and low-molecular nitrosothiols (LMNT) in the total amount of endogenous donors of NO in the aorta of old animals. Exposure of old animals to low doses of radiation resulted in an over 3-fold increase of LMNT. In old mice the levels of oxygen active forms, superoxide and hydroxyl radicals increase, while the level of H2O2 remained unchanged.

Aging↗

PubMed2005

[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.

Acute Disease↗

PubMed2004

[Acute myocardial ischemia-reperfusion injury: role of nitric oxide system].

In experiments on the closed-chest dogs it was shown that NOS inhibition resulted in the significant alterations of hemodynamic indices (coronary and peripheral vascular resistance, cardiac output and heart rate) under local myocardial ischemia/reperfusion in comparison with control experiments. At the first time it was shown that NOS inhibition activated the autophagic destruction of cardiomyocytes in the ischemic myocardium and could reduce an area of functionally active myocardium. L-arginine administration attenuated cardio- and hemodynamic disturbances, that substantially improved the course of ischemia/reperfusion, diminished the ultrastructural changes in myocardium and prevented development of autophagic programmed cell death.

Acute Disease↗

PubMed2004

[Human heart and endothelium functional activity depending on age and sex].

The complex study ofcardio-hemodynamics and functional activity of the endothelium in healthy persons of different age allowed us to establish that aging accompanied with a gradual worsening in the endothelium functioning with resulting increase in peripheral vascular resistance and blood pressure as well as decrease in the myocardial contractile activity. Such age shifts might be involved in pathogenesis of cardiovascular diseases, which prevalence is highly rises with increased age. Analysis of sex difference in the endothelium functioning showed a progressing lowering of the endothelium-dependent vasodilatory reaction to begin in the men as early as after 40 years of age. This leads to the decrease in the vasodilatory reserve with increase in peripheral vascular resistance and blood pressure. Worsening in the myocardial contractility in 40-year men can be also stipulated by changing in the endothelium synthetic activity that was evidenced by decrease in plasma levels of NO stable metabolites. In the women, such a lowering of the endothelium functional activity begins 10 years later and progresses more slowly compared to the men. The rate of worsening in the endothelium functioning in the men is twice of that in the women. Therefore, the elderly women have the endothelium to be 20 years "younger" than that in the elderly men, and perhaps namely this explains the better functioning of the cardiovascular system in the elderly women. So, a functional activity of the endothelium can be a main age and sex determinant, which stipulates well-known age and sex differences in prevalence of cardiovascular diseases and life expectancy. Prevention of the endothelium function disturbances might lead to the alignment of the differences between men and women in prevalence of cardiovascular diseases and life expectancy, decrease in general morbidity with improvement of life quality in elderly.

Adult↗

PubMed2004

[Sensitivity of phenylarsineoxide-induced mitochondrial permeability transition pore opening in the heart of old rats during intermittent hypoxic training].

We studied the sensitivity of mitochondrial permeability transition pore (MPTP) opening to its inductor-phenylarsineoxide (PAO) in adult (6 months), old rat heart (24 months) and in old rat heart under conditions of intermittent hypoxic training (IHT). We defined the sensitivity of MPTP opening on two parameters: the alterations in mitochondrial swelling and the release ofmitochondrial substances (mitochondrial factor). It was shown that mitochondria of old rat heart are more sensitive to PAO which caused opening of cyclosporin-sensitive MPTP and MPTP-dependent factor release, in comparison with those of adult rat heart mitochondria. One of the causes of increased sensitivity of MPTP opening to PAO is development of an oxidative stress with age that was accompanied by increase of an active metabolite of oxygen IHT on PAO-induced MPTP-opening and MPTP-dependent factor release from old rat heart mitochondria. IHT also reduced the content of H2O2 and *OH in old rat hearts. IHT can be used as protective procedure preventing MPTP opening in aging and, probably, in a numerous chronic pathological states of organism under oxidative stress.

Adaptation, Physiological↗

PubMed2004

[Inhibitors of arginase pathway in L-arginine metabolism as a new class of antihypertensive drugs: action of urea on oxidative and nonoxidative metabolism of L-arginine and vascular tone in chronic hypertension].

It has been studied an action of chronic urea introduction (40 mg/kg, 14 and 28 days) as arginase inhibitor on nonoxidative (arginase activity, urea, polyamines content) and oxidative (NOS activity, nitrite- and nitrate-anion content) metabolism of L-arginine in aorta, heart, plasma and erythrocytes of SHR. It has been shown that urea is an inhibitor of not arginase only, but also ornitinedecarboxilase (ODK) reactions, limiting L-arginine consumption for urea and polyamines synthesis and thus facilitating its utilization for nitric oxide synthesis by NOS. These exogenous effects of urea are not accompanied by amelioration of tissue ischaemization within cardiovascular system. It has been shown that exogenous urea down regulate blood pressure without any normalization of endothelim-dependent reactions of smooth muscle cells on acetylcholine in SHR.

Animals↗

PubMed2004

[Effect of modification in cell membrane fatty acid composition on adrenergic cardiac and vascular reactivity].

The work is dedicated to examination of the effect an omega-3 polyunsaturated fatty acids (PUFA) on vascular and cardiac reactivity in intact animals. In experiments on isolated perfused rat hearts and isolated rings of rat aorta it was shown that reactivity in rats with modified membranes was lesser than in control animals after adding norepinephrine in raising concentrations. Use of omega-3 PUFA resulted in the decrease of omega-6 PUFAs (arachidonic acid (AA)) content, while omega-3 PUFAs (EPA, DHA) content in cardiomyocytes membranes increased. Besides that it was shown that after omega-3 PUFA enriched diet NO3- content increased in cardiac tissues and blood.

Animals↗

PubMed2003

[Expression of iNOS and activities of iNOS and cNOS in right and left ventricles of the isolated heart during ischemia and reperfusion].

Isolated using Langendorff technique hearts of male Wistar rats were ischemized for 30 min and reperfused for 40 min. Both iNOS expression determined by immunoblotting, and its activity shown by a modified Griess method have been found to predominate in the right ventricle over the left one, as compared to cNOS activity which prevailed in the left ventricle. The latter significantly diminished after an ischemic injury in the left ventricle. On the contrary, an expression of iNOS and the total NOS activities increased progressively after ischemia and postischemic reperfusion; all the values in the right ventricle were higher than in the left one. The high level of iNOS expression in the right ventricle in a postischemic period decreased during reperfusion, although an activity of the enzyme went on elevating. These data can give an evidence for different regulation of NO synthesis in right or left ventricles of the heart, including normal conditions or ischemia.

Animals↗

PubMed2003

[Expression of markers of immunocompetent cells, cytokine level, and L-arginine metabolism in complex extremely high frequency and interferon therapy of inflammatory diseases in women of highlands].

Chronic inflammatory gynecological diseases (CIGD) in highlanders (2,100-2,200 m a.s.l.) are accompanied with the following changes in immunoregulatory parameters: strengthening in the expression of CD3+ (TCR), CD4+ (T-helpers), CD16+ (NK-cells), CD25+ (activated IL-2R), increase in CD4+/CD8+ ratio, levels of circulating cytokines--alpha-, beta-, gamma-interferon (IFN) and alpha-, beta-tumor necrotizing factor (TNF), strengthening in immune adhesion of thrombocytes (IAT), and inhibition of the oxidative metabolic way of L-arginine with redistribution of the main metabolites formed via its non-oxidative way. Complex extremely high frequency (EHF) therapy and interferon (with Laferon) therapy of CIGD normalized expression of the differentiated and functional CD-markers of immunocompetent cells (ICC), CD4+/CD8+ ratio, increased expression of CD8+, decreased IAT and levels of circulating cytokines (IFN, TNF), changed L-arginine metabolism with activation of the oxidative way. Full-value of the population signs of immune stabilization due to the treatment was complemented with increase in the ICC functional parameters--markers of mitochondrial, lysosomal and mitotic activity. We first demonstrated a high effectiveness of complex use of EHF and Laferon as an immunocorrective therapy of CIGD in highlanders.

Adult↗

PubMed2003

[Changes in vasodilator responses of vascular smooth muscles and nitric oxide system in experimental diabetes mellitus].

The experimental data of endothelium-dependent and endothelium-independent responses of vascular smooth muscles of isolated preparations of the thoracic aorta of rats with experimental diabetes mellitus (streptozotocin-induced diabetes) and a control group of animals are presented in the article. It has been shown that at diabetes mellitus endothelium-dependent vasodilation was deteriorated to the most extent. It resulted from dysfunction of the endothelium due to a reduce in the synthesis of NO. This conclusion was based on the data of the parameters of the contents of steady metabolites of nitric oxide (NO2- and NO3-), as well as activities of inducible and constitutive NO-synthases (iNOS and cNOS) in heart, aorta, erythrocytes and blood plasma in diabetic and control animals.

Animals↗

PubMed2003

[Effect of modification in fatty acid composition of membrane phospholipids on reaction of isolated heart in acute ischemia-reperfusion].

The aim of this study was to evaluate the effects of a diet supplemented with omega-3 polyunsaturated fatty acids (eicosapentaenoic and docosahexaenoic) and tocopherol, which are the base of a preparation "Tekom", on a composition of myocardial phospholipid fatty acids, as well as on the metabolism of eicosanoids, free radical processes and the contractility of isolated working heart in rats at ischemia/reperfusion. Added to the diet within 4 weeks, "Tekom" induced an increase in the content of omega-3 polyunsaturated fatty acids in membranes of cardiomyocytes, a decrease in vasoactive metabolites of arachidonic acid and limitation of free radical processes. "Tekom" inhibited cardiac arrhythmias in the isolated working hearts of rats and improved the cardiac pump function at ischemia/reperfusion.

Administration, Oral↗