hypoxia activation by chronic intermittent

SUMMARY AND PERSPECTIVE Although clinical studies have shown that recurrent apneapatients exhibit sympathetic activation, the underlying mecha-nisms are not known. In recent years, studies using experimen-tal models of IH, the hallmark of apnea, provided importantinsightsintothemechanismsassociatedwithsympatho-adrenalactivation by chronic IH. There is a general agreement thataugmented arterial chemoreflex contributes to the sympatheticactivation by CIH. The CIH-induced chemoreflex activation is,in part, due to remodeling of the carotid body chemoreceptorfunction. In addition to the chemoreflex, evidence is emergingthat CIH leads to attenuated baroreflex function, which is, inpart, due to reduced carotid baroreceptor activity. Thus animbalance between the chemo- and the baroreflex seems to bea major contributor to sympathetic activation by CIH. Evi-dence is emerging that CIH leads to reconfiguration of thecentral neuronal networks associated with sympathetic activa-tion. A major advance in the field of apnea research is theidentification of ROS as a major cellular mechanism mediatingthe adverse consequences of CIH on sympathetic function.However, the mechanism(s) underlying ROS generation byCIH, especially in the CNS, need further studies. Studies oncell cultures and rodents led to the identification of HIFs as oneof the major molecular mechanisms contributing to sympatho-adrenal activation by CIH. Further studies are needed foridentifying the role(s) of other transcriptional activators, inter-actions between the transcriptional activators, and identifica-tion of downstream target genes associated with autonomicdysfunction caused by CIH.