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E B Manukhina

Publications and source records attributed to E B Manukhina.

At least 19 recordsLinked to original sources
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↗
PubMed1998

[Selective inhibition of inducible NO-synthase by nonselective inhibitor].

The study has shown that Nw-nitro-L-arginine, a nonselective nitric oxide (NO) inhibitor, in low non-vasoactive doses (10 mg/kg) exerted a protective effect in heat shock as demonstrated by a decrease in the mortality rate and prevention of acute hypotension in rats. The L-NNA in the same dose inhibited the basal NO production but left unaffected a carbachol-activated NO production. The findings suggest a possibility in principle of preferential inhibition of inducible NO-synthase in pathological conditions related to the NO overproduction using non-vasoactive doses of L-NNA the nonselective NO-synthase inhibitor.

Animals↗
PubMed1998

Stress, adaptation, and nitric oxide.

The biological role of nitric oxide (NO) has been studied for more than ten years. Nevertheless, the number of investigations in this field continues to increase. It is now suggested that NO is a previously unrecognized, very important regulator of physiological functions and cell metabolism in the body. Through the application of the methods of molecular biology, more and more data are being accumulated on the regulatory role of NO in the mechanism of gene expression and protein biosynthesis. The data presented in this review show an important role of NO in stress and adaptive responses of organisms and thereby expand existing notions on the biological role of this unique molecule. This review substantiates the idea that the system of NO generation is a newly discovered stress-limiting system. The action of this NO-ergic system is based on the capability of NO to limit key links of the stress reaction and to enhance the potency of endogenous defense systems of the organism. The role of NO is considered at the major stages of adaptation: 1) at the urgent stage related with the stress reaction; 2) at the stage of the transition from urgent to long-term adaptation; and 3) at the stage of long-term adaptation characterized by the formation of stable protective effects. It is demonstrated that pharmacological "imitation" of the activated NO-ergic system by administration of NO donors to the organism provides in many instances an efficient protection against stress damage and enhances the adaptive capacity of the organism.

Adaptation, Physiological↗
PubMed1996

Nitric oxide donor induces HSP70 accumulation in the heart and in cultured cells.

As our group has shown, the NO-synthase inhibitor L-NNA decreased 2-3 times heat shock-induced synthesis of the heat shock protein HSP70 (FEBS Lett. 370 (1995) 159-162). It was suggested that NO is involved in such induction. In the present study, it was found that (1) injection of the NO donor dinitrosyl iron complex (DNIC) into rats results in accumulation of HSP70 in the heart; (2) heat shock is accompanied by increased generation of NO (EPR assay) and HSP70 accumulation in cultured cells; (3) DNIC induces HSP70 accumulation in cultured cells not exposed to heat shock.

Animals↗
PubMed1996

Physical properties of dinitrosyl iron complexes with thiol-containing ligands in relation with their vasodilator activity.

When studying the vasodilator activity of dinitrosyl iron complexes (DNIC) with thiol-containing ligands as NO donors, it should be taken into consideration that these complexes depending on the content of thiols in the environment can occur in either of two forms that differ by their EPR, gamma-resonance and optical characteristics and also by their vasodilator effect on isolated blood vessels. The more stable diamagnetic form appears at the ratio Fe2+:RS- = 1:2. It reversibly dissociates to the monomeric paramagnetic form [(RS-)2Fe+(NO+)2] on increasing the thiol content to the level 20-times and more exceeding the quantity of iron. It is suggested that stabilization of the dimeric form is provided by formation of RS(-)-NO+ bonds between monomeric components of the dimer. This process is favored by a corresponding orientation of the monomers relative to each other. A high stability of the DNIC dimeric form correlates with more prolonged vasodilator effect of this complex as an NO source. Replacement of cysteine by reduced glutathione in dimeric and monomeric forms of DNIC increases both stability of the complexes and the duration of their vasodilator effect.

Animals↗