[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.
Kurhaliuk
N M
NM
Kotsiuruba
A V
AV
Sahach
V F
VF
D000208:Acute Disease; D000818:Animals; D015317:Biogenic Polyamines / Q000378:metabolism; D002952:Citric Acid Cycle; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D000860:Hypoxia / Q000097:blood / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis*; D009573:Nitrites / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D019802:Succinic Acid / Q000494:pharmacology
D015317:Biogenic Polyamines; D007656:Ketoglutaric Acids; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D019802:Succinic Acid