Role of Proinfl ammatory Factors, Nitric Oxide, and Some Parameters of Lipid Metabolism in the Development of Immediate Adaptation to Hypoxia and HIF-1α Accumulation

The development of immediate and delayed long-term resistance to hypoxia during a course of intermittent normobaric hypoxia (15 daily sessions of alternating exposure to 10% O₂ and atmospheric air for 1 h) correlated with biphasic expression of HIF-1α in neocortex of hypoxia-intolerant rats, which suggests involvement of this protein factor not only in the formation of long-term adaptation, but also in triggering immediate adaptation to hypoxia. Both processes develop under conditions promoting down-regulation of oxidative modifi cation of LDL and increasing tolerance of biological membranes to hypoxia in the absence of activation of the free radical processes, which therefore do not trigger HIF-1α expression under these conditions. Neither cytokines nor NO are the inducers of immediate adaptation, and they are not related to HIF-1α expression during the early post-hypoxic period. In contrast, long-term adaptation in response to the course of intermittent normobaric hypoxia develops against the background of enhanced NO production, activation of pro- and anti-infl ammatory factors, and expression of VEGF, the marker of angiogenesis. Therefore, all these factors can promote activation of transcription processes required to form the long-term adaptation.