[The production and deposition of nitric oxide during adaptation to hypoxia].

It is common knowledge that adaptation to hypobaric hypoxia provides for a number of protective NO-dependent effects in the organism. However, many aspects of its influence on NO metabolism remain unclear. In this work we studied the relationship between NO production and deposition in the course of adaptation to hypoxia.

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.

[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.

Interaction of peroxynitrite and hydrogen peroxide with dinitrosyl iron complexes containing thiol ligands in vitro.

The interaction of peroxynitrite with thiolate dinitrosyl iron complexes (DNIC) has been examined and compared with the interaction with H2O2. Peroxynitrite oxidized DNIC containing various thiolate ligands--cysteine, glutathione, and bovine serum albumin. Analysis of the oxidation suggested a two-electron reaction and gave third-order rate constants of (9.

[Nitric oxide in the rat cerebral cortex in seizure models: potential ways of pharmacological modulation].

Seizures induced with Thiosemicarbaside, Pentylenetetrasole, N-methyl-D,L-aspartate were used as models. The NO content increased 4-5-fold in the brain cortex at the peak of seizures. The increase could be prevented by pre-treatment with N-nitro-L-arginine and the seizures were weakened.

The 2.03 signal as an indicator of dinitrosyl-iron complexes with thiol-containing ligands.

The parameters of EPR signal from dinitrosyl-iron complexes (DNIC) with bovine serum albumin (BSA), horse hemoglobin (Hb), and apometallothionein (apo-Mt) of horse kidney incorporating one (BSA, Hb) or two thiol-containing ligands (apo-Mt) were compared. The EPR signal from DNIC-BSA was characterized by the rhombic symmetry of g tensor at room temperature of signal recording (ambient temperature) or at 77K in the solution frozen in the presence of glycerol. In freezing of the solution in the absence of glycerin, under the exposure of DNIC-BSA to negatively charged sodium dodecyl sulfate (SDS) ions, or in the incorporation of DNIC-BSA into the reversed micelles formed by negatively charged ions of surfactant aerosol OT, the symmetry of the g tensor of DNIC-BSA EPR signal increased to axial.

[NO-Dependent mechanisms of adaptation to hypoxia].

Studies of nitrogen oxide (NO)-dependent mechanisms of organism resistance to hypoxia demonstrate that (1) acute hypoxia induces NO hyperproduction in the brain and does not affect NO production in the liver; (2) adaptation to hypoxia decreases NO production in the liver and brain; and (3) adaptation to hypoxia prevents NO hyperproduction in the brain and enhances NO synthesis in the lever during acute hypoxia. An NO donor--dinytrosyl iron complexes (DCI, 200 micrograms/kg, single intravenous (i.v.

Dinitrosyl iron complexes and S-nitrosothiols are two possible forms for stabilization and transport of nitric oxide in biological systems.

The physicochemical properties, mechanisms of synthesis and decomposition of dinitrosyl iron complexes (DNICs) with thiol-containing ligands and of S-nitrosothiols (RS-NO), and the potential role of these compounds in storage and transport of NO in biological systems are reviewed. Special attention is given to the phenomenon of mutual transformation of DNIC and RS-NO catalyzed by Fe2+. Each Fe2+ binds two neutral NO molecules in the DNICs, catalyzes their mutual oxidation--reduction with formation of nitrous oxide and nitrosonium ions appearing in the DNICs.

Biological role of nitric oxide: history, modern state, and perspectives for research.

This paper is an introduction to this issue of review papers on the biological role of nitric oxide. The history, modern state, and promising directions for research in this field are briefly considered.

[Prevention of nitric oxide hyperproduction by adaptation to stressor effects].

As was shown earlier, acute hypotensive shock induced by nitrogen oxide (NO) hyperproduction can be prevented by dosed adaptation to environmental factors. In this work we tested the hypothesis that the mechanism of this adaptive effect is based on limiting NO hyperproduction. It was shown that rat adaptation to stress completely prevented arterial depression and sharply increased revival rate of the animals after heat shock.

[The seizures induced by N-methyl-D,L-aspartate administration are accompanied by an enhancement of nitric oxide generation and of lipid peroxidation processes in the rat brain].

EPR-spectrometry was performed to study the nitrous oxide (NO) content and the intensity of lipid peroxidation (LPO) in the brain cortex of rats during convulsions induced by intracerebral injection of N-methyl-D,L-aspartate (NMDLA). It was shown that the convulsions were attended with a fourfold increase in the NO content and activation of LPO in the rat brain cortex. Disocilpin injection fully prevented the development of convulsions as well as increase in the NO level and LPO activation caused by NMDLA injection.

[Nitric oxide as a factor in the antihypoxic effect of adaptation to physical loading].

It is known that adaptation to exercise enhances the organism resistance to acute hypoxia. However the mechanism of this cross protective effect have been insufficiently studied. The analysis of literature suggests that NO may play a role in the development of the antihypoxic effect of adaptation to exercise.

Effect of nitroso compounds on Na/K-ATPase.

Thiol containing NO.-derivatives were found to inhibit the activity of brain and kidney Na/K-ATPase. S-Nitrosogluthatione demonstrated only minor inhibiting activity, while dinitrosyl iron complexes (DNIC) with cysteine or glutathione were much more effective.