[Phase changes in energy metabolism during periodic hypoxia].

Male Wistar rats were exposed to periodic hypobaric hypoxia (PHH), by "lifting" in barochamber at "altitude" 5600 m for 1 h every 3 days (6 séances). The dynamics of changes in oxygen consumption (VO2), and body temperature (Tm), as well as in HIF-1alpha and HIF-3alpha gene expression, and mitochondrial respiration in the ventricles of the heart was studied. On the basis of the data we identified four phases of the physiological changes. The first phase, hypometabolic (1-3 séances), is characterized by decrease in VO2 and Tm, induction of HIF-1alpha and HIF-3alpha with delayed transient stimulation of metabolism in response to each séance of hypoxia. In heart mitochondria, V3 and V4 are increased, but V3/V4 and ADP/O are reduced. During the second phase, transitional (3-4 séances), there is reorganization of metabolism and decrease its hypoxic reactivity. The third phase, hypermetabolic (4-5 séances), is characterized by intensification of metabolism and compensation of hypoxic disorders. The fourth phase (after 5 séance) - is a state of metabolic adaptation with normalization of VO2 and Tm, expression of HIF-1alpha and HIF-3alpha, mitochondrial respiration, increased NAD-dependent oxidation of carbohydrate and lipid substrates. Thus, during PHH consequent rebuilding of processes of oxygen transport, tissue respiration and thermogenesis occurs, mediated by induction of the HIF subunits.