Role of proinflammatory 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 modification 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-inflammatory 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.