[Exogenous L-arginine modulates mitochondrial and microsomal oxidation in acute and intermittent normobaric hypoxia]

Abstract

It is known that protective effects of adaptation to intermittent hypoxia are mediated partly by stimulating of some mitochondrial and microsomal enzymes activity. Our objective was to investigate whether exogenous NO (L-arginine) or NO blocker (L-NNA) modulate mitochondrial and microsomal oxidation during acute hypoxia (AH) and intermittent hypoxic training (IHT). In control rats AH (inhalation of 7% O2, 30 min) provoked a decrease of ADP-stimulated liver mitochondrial respiration. However, the pattern of oxidation substrates was different from normoxic controls. In the presence of succinate, an increase of the Chance respiratory coefficient and the phosphorylation rate and a decrease of O2 uptake efficacy with simultaneous activation of aspartate aminotransferase activity were observed. Simultaneously, oxidation of a-ketoglutarate, an NAD-dependent substrate, was inhibited. IHT caused reorganization of mitochondrial energy metabolism favoring NAD-dependent oxidation and improving the protection against acute hypoxia. After 14 days of normobaric IHT (10% O2, 15-min sessions with 15 min rest intervals, 5 times daily), in comparison to controls acute hypoxic challenge in the presence of succinate resulted in an increase of the Chance respiratory coefficient, the ADP/O ratio and the phosphorylation rate, in activation of both aspartate and alanine aminotranferases, and in less lipid peroxidation. The microsomal oxidation was not changed under AH per se but significantly decreased (by 37%) during acute hypoxic test after ITH. These findings indicated a more efficient use of oxygen under hypoxic conditions after IHT pre-conditioning. The combination of IHT with L-arginine treatment (600 mg/kg intraperitoneally, daily before IHT sessions) provoked more pronounced decrease of tissue oxygen consumption and microsomal oxidative processes in comparison with IHT animals. L-arginine effects were abolished by the NO-synthase blocker L-NNA. We conclude that the combination of IHT with NO-donor treatment provokes a decrease in aerobic link of energy regulation thereby increasing the tolerance to episodes of acute hypoxia.