RESPONSE TO ACUTE HYPOXIA: A Challenge to Mimic Disease
Because hypoxia affects human physiology at multiple levels ranging from
reflex mechanisms, such as the peripheral chemoreflex, to specific
cellular pathways regulated through oxygen, experimental hypoxia could
have utility in clinical research in various settings. Tonic
chemoreceptor hyperactivity with subsequent sympathetic nervous system
activation has been implicated in the pathogenesis of arterial
hypertension [56]. Thus, peripheral chemoreceptor modulation could
have therapeutic utility in this condition, particularly in patients not
responding sufficiently to established therapies [57]. Recent
studies demonstrated that acute hypoxia during high-resolution
functional magnetic resonance imaging (fMRI) can be used to trace
peripheral chemoreceptor responses in human beings [58]. Because
changes in CO2 confound the response to hypoxic
peripheral chemoreceptor stimulation, isocapnic hypoxia protocols have
been proven useful in clinical research [59].
Acute hypoxia can also be used to test the tolerance in patients or
those in occupational settings such as in fighter pilots. Moreover,
hypoxia may produce a phenotype resembling a clinical condition, which
could then be utilized to probe new therapies. However, hypoxia may also
regulate a disease-relevant signaling pathway. Indeed, hypoxia plays a
major role in a multitude of human diseases, either as a result of the
disease, like in the case of pulmonary dysfunction, or by modifying the
disease process as seen in some forms of cancer, where local hypoxia may
affect differentiation of the tumor to more aggressive phenotypes
[60].
PULMONARY ARTERIAL
HYPERTENSION