[Hypoxia and nitric oxide]

Cell death or survival under hypoxia is determined to a greater extent by the nature of changes in nitric oxide (NO) metabolism. Severe hypoxia causes NO overproduction that is an important factor that induces apoptotic cell death. In contrast, a cell response to moderate hypoxia enhances hypoxic resistance and restricts the mechanisms of activated apoptosis. A moderate increase in NO synthesis and storage that are characteristic of hypoxic adaptation may limit NO overproduction induced by acute hypoxia. In addition, NO-dependent mechanisms of adaptation are apparently involved in the restriction of apoptosis-specific signaling pathways. Therefore, during hypoxic adaptation, NO acts as an endogenous protective agent involved in the limitation of severe hypoxia-induced cell damages.