Biomedical subjects

E B Manukhina

Publications and source records attributed to E B Manukhina.

At least 19 recordsLinked to original sources

PubMed2001

[Correction of NO-dependent cardiovascular disorders by adaptation to hypoxia].

Spontaneously hypertensive rats (SHR-SP) were adapted to intermittent hypobaric hypoxia in an altitude chamber for 40 days. The adaptation to hypoxia prevented an excessive endothelium-dependent relaxation and hypotension characteristic of myocardial infarction. The adaptation also attenuated the increase in blood pressure and prevented impairment of the endothelium-dependent relaxation in SHR-SP. The universal nature of the adaptation allows to use it for correcting many cardiovascular disorders related to diverse alterations of NO metabolism.

Adaptation, Physiological↗

PubMed2000

[Nitric oxide synthesis in patients with myocardial infarction].

The findings of the author demonstrate that the system of nitric oxide (NO) generation and metabolism is an element of multicomponent response of the organism to myocardial infarction (MI). This response consists in MI patients' systemic ability and, in particular, their peripheral blood mononuclears' ability to produce NO as well as the absence of iNOS activation in peripheral blood of MI patients. It is important for a practitioner to understand that a fall in the urine and plasma concentration of NO metabolism end product reflects low activity of NO generation while NO is a powerful regulatory factor in the cardiovascular system. Thus, low levels of NO and its metabolites in the urine and plasma of MI patients indicate depletion of compensatory coronarodilatating potential and, eventually, poor prognosis. Relevant measurements will provide additional parameters in assessment of body reserves in MI patients and in MI prognosis within the first hours of its onset.

Adult↗

PubMed2000

Role of nitric oxide in adaptation to hypoxia and adaptive defense.

Adaptation to hypoxia is beneficial in cardiovascular pathology related to NO shortage or overproduction. However, the question about the influence of adaptation to hypoxia on NO metabolism has remained open. The present work was aimed at the relationship between processes of NO production and storage during adaptation to hypoxia and the possible protective significance of these processes. Rats were adapted to intermittent hypobaric hypoxia in an altitude chamber. NO production was determined by plasma nitrite/nitrate level. Vascular NO stores were evaluated by relaxation of the isolated aorta to diethyldithiocarbamate. Experimental myocardial infarction was used as a model of NO overproduction; stroke-prone spontaneously hypertensive rats (SHR-SP) were used as a model of NO shortage. During adaptation to hypoxia, the plasma nitrite/nitrate level progressively increased and was correlated with the increase in NO stores. Adaptation to hypoxia prevented the excessive endothelium-dependent relaxation and hypotension characteristic for myocardial infarction. At the same time, the adaptation attenuated the increase in blood pressure and prevented the impairment of endothelium-dependent relaxation in SHR-SP. The data suggest that NO stores induced by adaptation to hypoxia can either bind excessive NO to protect the organism against NO overproduction or provide a NO reserve to be used in NO deficiency.

Adaptation, Physiological↗

PubMed2000

Cross-talk between nitric oxide and HSP70 in the antihypotensive effect of adaptation to heat.

In this work, we evaluated the effect of adaptation to heat on the fall of blood pressure (BP) induced by heat shock (HS) and the interrelation between nitric oxide (NO) and heat shock protein, HSP70. Experiments were carried out on Wistar rats. It was shown that HS resulted in a generalized and transient increase in NO production (the electron paramagnetic resonance method) and a fall of BP from 113+/-3 to 88+/-1 mm Hg (p<0.05). Adaptation to heat itself did not affect BP, but completely prevented the NO overproduction and hypotension induced by HS. The adaptation simultaneously increased the brain NO-synthase content and induced HSP70 synthesis (the Western blot analysis) in various organs. Both the antihypotensive effects of adaptation and HSP70 accumulation were completely prevented by L-NNA, an inhibitor of NO synthesis, or quercetin, an inhibitor of HSP70 synthesis. The data suggest that adaptation to heat stimulates NO synthesis and NO activates synthesis of HSP70. HSP70, which hampers NO overproduction, thus restricts the BP fall induced by heat shock.

Adaptation, Physiological↗

PubMed2000

[Nitric oxide storage in rats of various genetic strains and its role in the antistressor effect of adaptation to hypoxia].

Adaptation to hypobaric hypoxia induced a gradual increase in the NO production along with a progressive NO storage in vascular wall. Unadapted August rats were more resistant against stress-induced stomach ulceration than the Wistar rats. Following a 6-day adaptation rats of both strains revealed a protective antiulcerogenic effect. A long-term adaptation potentiated the stress damage of the stomach rather than protected against it. A higher basal NO production seems to provide a more efficient antistress defence in the August rats. An intense NO storage may create a relative NO shortage and thus predispose to stress-induced vasoconstriction and ulceration.

Adaptation, Physiological↗

PubMed2000

[Nitric oxide in the cardiovascular system: its role in adaptive protection].

Nitric oxide (NO) is involved virtually in all processes occurring in the body. In the cardiovascular system, it regulates cardiac contractility, blood coagulability, cell proliferation, vascular tone, and blood pressure (BP). NO deficiency leads to the development of severe cardiovascular diseases associated with endothelial dysfunction, abnormally increased vascular tone and BP (such as hypertension, angina pectoris, atherosclerosis, diabetic angiopathy, etc.) At the same time, NO hyperproduction makes a contribution to the development of septic, cardiogenic, thermal, and other shocks. The most effective non-drug stimulation of NO synthesis is a gradual adaptation to environmental factors. The adaptation-induced elevation of NO levels, followed by vascular wall NO deposition, on the one hand, limits the damaging action of excess NO in shocks by the feedback, and, on the other, makes up some NO reserve which may be used in NO deficiency. Further studies of NO-dependent adaptive mechanisms will allow the agent to be used in the prevention and treatment of cardiovascular diseases associated with NO metabolic disturbances.

Adaptation, Physiological↗

PubMed2000

[Nitrogen oxide storage as a factor of adaptive defence].

Adaptation to environmental factors possesses multiple NO-dependent protective effects and stimulates the NO storage. An adaptation to a mild stress was shown to reduce the death rate in rats from 57% to 8% and to prevent a heat shock-induced hypotension and endothelial overactivation. Treatment of the rats with the NO-synthase inhibitor L-NNA interfered with the NO storage and formation of protective effects, while the NO donor dinitrosyl iron complex facilitated the NO storage and simulated the adaptive defence. The data obtained suggest an important role of the NO storage in adaptive defence of the organism.

Adaptation, Physiological↗

PubMed2000

[Hypoxia and nitric oxide].

Cell death or survival under hypoxia is determined to a greater extent by the nature of changes in nitric oxide (NO) metabolism. Severe hypoxia causes NO overproduction that is an important factor that induces apoptotic cell death. In contrast, a cell response to moderate hypoxia enhances hypoxic resistance and restricts the mechanisms of activated apoptosis. A moderate increase in NO synthesis and storage that are characteristic of hypoxic adaptation may limit NO overproduction induced by acute hypoxia. In addition, NO-dependent mechanisms of adaptation are apparently involved in the restriction of apoptosis-specific signaling pathways. Therefore, during hypoxic adaptation, NO acts as an endogenous protective agent involved in the limitation of severe hypoxia-induced cell damages.

Animals↗

PubMed2000

The function of endogenous protective systems in patients with insulin-dependent diabetes mellitus and polyneuropathy: effect of antioxidant therapy.

alpha-Lipoic acid is a very efficient antioxidants for the treatment and prevention of diabetic neuropathy. The aim of the present study was to evaluate the function of nitric oxide (NO) and stress proteins (HSP72) in insulin-dependent diabetes complicated by polyneuropathy and possible contribution of these systems to the therapeutic effects of alpha-lipoic acid. Plasma content of nitrites and nitrates in diabetic patients was almost 2-fold below the normal. The treatment with alpha-lipoic acid completely normalized the plasma content of these stable NO metabolites. The majority of patients had also low level of HSP72. Positive clinical effects of alpha-lipoic acid were accompanied by normalization of HSP72 synthesis. Thus, activation of the NO and HSP protective systems is involved in the therapeutic effect of alpha-lipoic acid in diabetic patients (type 1 diabetes mellitus) with polyneuropathy.

Adolescent↗

PubMed2000

[Stress-limiting nitric oxide system].

The work substantiates a concept of the nitric oxide (NO) system as a universal transmitter and controller of physiological functions and as a new stress-limiting system. The NO system can be activated by a stress, restrict release and/or production of stress hormones, restrict the stress damage to the organism, enhance the organism's resistance against stress, can be activated in adaptation to repeated exposure to environmental factors. Some specifics of the NO system differing it from other stress-limiting systems, are discussed.

Adaptation, Physiological↗

PubMed1999

NO-dependent mechanisms of adaptation to hypoxia.

In studying NO-dependent mechanisms of resistance to hypoxia, it was shown that (1) acute hypoxia induces NO overproduction in brain and leaves unaffected NO production in liver of rats; (2) adaptation to hypoxia decreases NO production in liver and brain; and (3) adaptation to hypoxia prevents NO overproduction in brain and potentiates NO synthesis in liver in acute hypoxia. Dinitrosyl iron complex (DNIC, 200 microg/kg, single dose, iv), a NO donor, decreases the resistance of animals to acute hypoxia by 30%. Nomega-nitro-L-arginine (L-NNA, 50 mg/kg, single dose, ip), a NO synthase inhibitor, and diethyl dithiocarbamate (DETC, 200 mg/kg, single dose, iv), a NO trap, increases this parameter 1.3 and 2 times, respectively. Adaptation to hypoxia developed against a background of accumulation of heat shock protein HSP70 in liver and brain. A course of DNIC reproduced the antihypoxic effect of adaptation. A course of L-NNA during adaptation hampered both accumulation of HSP70 and development of the antihypoxic effect. Therefore, NO and the NO-dependent activation of HSP70 synthesis play important roles in adaptation to hypoxia.

Adaptation, Physiological↗

PubMed1999

Production and storage of nitric oxide in adaptation to hypoxia.

Adaptation to hypobaric hypoxia is known to exert multiple protective effects related with nitric oxide (NO). However the effect of adaptation to hypoxia on NO metabolism has remained unclear in many respects. In the present work we studied the interrelation between NO production and storage in the process of adaptation to hypoxia. The NO production was determined by the total nitrite/nitrate concentration in rats plasma. The volume of NO store was evaluated in vitro by the magnitude of isolated aorta relaxation to diethyldithiocarbamate. It was shown that both the nitrite/nitrate level and the NO store increased as adaptation to hypoxia developed. Furthermore, the NO store volume significantly correlated with plasma nitrite/nitrate. Therefore, adaptation to hypoxia stimulates NO production and storage and these effects can potentially underlie NO-dependent beneficial effects of adaptation.

Adaptation, Physiological↗

PubMed1999