title: [Regulation of oxidative phosphorylation by liver mitochondria receptors after adaptation by rats to periodic normal pressure and acute hypoxia].
abstract: It is known that NO-dependent mechanisms are involved in mitochondrial adaptive reactions to different factors. The object of this study was to investigate the role of cholino- and adrenoreceptors in NO-dependent reactions of rat liver mitochondria to acute hypoxia (AH) and intermittent hypoxic training (IHT). Eight groups of Wistar male rats participated in the study. Animals of Gr. I underwent daily i.p. saline injections during 14 days. Gr. II was examined after a single AH test (inhalation of 7% O2, 30 min) with the same saline treatment. Another six groups were exposed to IHT (11% O2, 15-min sessions with 15 min rest intervals, 5 times daily during 14-days), at that 15 min before every IHT session animals underwent i.p. treatment: Gr. III and IV--saline, Gr. V--L-arginine, Gr. VI--NO synthase blocker L-NNA, Gr. VII--L-arginine with alpha-, beta-adrenoblockers phentolamine and obzidane, Gr. VIII--L-arginine with M- and N-cholinoreceptor blockers athropine and benzohexonium. After IHT Gr. IV-VIII were exposed to a single AH test and decapitated just after that. In control rats AH provoked: 1) in the presence of succinate, a 33% augmentation of ADP-stimulated mitochondrial respiration (V3) with a 18% decrease of O2 uptake efficiency (ADP/O ratio); 2) in the presence of alpha-ketoglutarate, a NAD-dependent substrate, no changes in V3 were observed, also 21% augmentation of ADP/O ratio registered. These events were accompanied by 36% increase in succinate dehydrogenase (SDG) activity, two-fold augmentation of malon dialdehyde (MDA) content and 43% increase in diene conjugates (DK). IHT caused reorganization of mitochondrial energy metabolism improving the protection against acute hypoxia. A decrease by 40% in activation of mitochondrial respiration in the presence of succinate (V3--by 40% and V4--by 34%), a reduction of MDA and DK content (by 32% and 20%, respectively), an increase in SGD activity by 31% was observed in Gr. IY compared to Gr. II. Extra exogenous NO (Gr.Y) did not influence V3 and V4 in the presence of succinate, but in the presence of alpha-ketoglutarate decreased them by 9% and 29%, respectively, as well as ADP/O ratio by 28% on the background of SDG inhibition by 24% and the decrease of MDA content by 34%, that is reduced aerobic energy supply and reactive oxygen species production. L-arginine effects were abolished by L-NNA. Effects of cholinoreceptor blockers over L-arginine (Gr. VIII) resembled effects of AH: considerable activation of succinate and alpha-ketoglutarate oxidation in stage V3 by 44% and 75%, respectively, was observed which was accompanied by a decrease in ADP/O by 21% and 31%, and V3/V4 by 15% and 28%, respectively, in comparison to Gr.Y. It indicates that effects of L-arginine are mediated mainly by cholinoreceptors. The effects of adrenoreceptors blockade strengthened the combined effects of IHT with L-arginine treatment, confirming primary role of cholinoreceptors in NO-dependent mitochondrial reactions to IHT. Thus, oxygen uptake and its effective usage depend on dynamic status of adreno- and cholinoreceptors. We conclude that protective effects of the combination of IHT with NO-donor treatment under acute hypoxia are mainly realized through cholinoreceptors.
authors.affiliation: Ivan Franko Lviv National University, Ukraine.
authors.forename: N M
authors.initials: NM
authors.lastname: Kurhaliuk
authors.forename: T V
authors.initials: TV
authors.lastname: Serebrovs'ka
authors.forename: Ie E
authors.initials: IeE
authors.lastname: Koliesnikova
mesh_terms: D000222:Adaptation, Physiological; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000531:Altitude; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010085:Oxidative Phosphorylation; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D006584:Hexamethonium Compounds; D018727:Muscarinic Antagonists; D011941:Receptors, Adrenergic; D011950:Receptors, Cholinergic; D019323:omega-N-Methylarginine; D001285:Atropine; D001120:Arginine; D011433:Propranolol; D013385:Succinate Dehydrogenase; C021628:benzohexonium; D010646:Phentolamine