ABSTRACT

Male Wistar rats were exposed to periodic hypobaric hypoxia (PHH) by "lifting" in hyperbaric chamber at "altitude" 5,600 m for 1 with an interval of 3 days (6 sessions). Dynamics of oxygen consumption (VO₂), and body temperature (Tb), as well as HIF-1α, HIF-3α gene expressions, and mitochondrial respiration in the ventricles of the heart were studied. Based on these results, we have identified four phases of physiological, biochemical and genetic changes. The first phase, hypometabolic (sessions 1 − 3), is characterized by decreased VO₂ and Tb, induction of HIF-1α and HIF-3α with delayed transient stimulation of metabolism in response to each hypoxia session. In the heart mitochondria, the rates of phosphorylation (V3) and controlled respiration (V4) are increased, while the respiratory control (V3/V4) and the ADP /O ratio are reduced. In the second, transitional phase (sessions 3 − 4), reorganization of of oxidative metabolism and a decrease in hypoxic reactivity occur. The third phase, hypermetabolic (sessions 4 − 5), is characterized by increased metabolism and compensation of hypoxic disorders. The fourth phase (after session 5) is a state of metabolic adaptation with normalization of VO₂ and Tb, HIF-1α and HIF-3α gene expressions, mitochondrial respiration, as well as increased NAD-dependent oxidation of carbohydrate and lipid substrates. Thus, during PHH, consistent restructuring processes of oxygen transport, tissue respiration and thermogenesis, mediated by induction of HIF subunits, occur./sub