To the majority of the population, recurrent episodes of
hypoxia are more likely encountered in life than sustained
hypoxia. Until recently, much of the information on the long-term effects of intermittent
hypoxia has come from studies on human subjects experiencing chronic recurrent
apneas. Recent development of animal models of intermittent
hypoxia and techniques for exposing cell cultures to alternating cycles of
hypoxia have led to new information on the effects of episodic
hypoxia on
oxygen-sensing mechanisms in the carotid body chemoreceptors and regulation of gene expression. The purpose of this review is to highlight some recent studies on the effects of intermittent
hypoxia on
oxygen sensing at the carotid bodies and regulation of gene expression. In a rodent model, chronic intermittent
hypoxia selectively enhances hypoxic sensitivity of the carotid body chemoreceptors. More interestingly, chronic intermittent
hypoxia also induces a novel form of plasticity in the carotid body, leading to long-term facilitation in the sensory discharge. Studies on cell cultures reveal that intermittent
hypoxia is more potent in activating
activator protein-1 and
hypoxia-inducible factor-1
transcription factors than sustained
hypoxia. Moreover, some evidence suggests that intermittent
hypoxia utilizes intracellular signaling pathways distinct from sustained
hypoxia.
Reactive oxygen species generated during the reoxygenation phase of intermittent
hypoxia might play a key role in the effects of intermittent
hypoxia on carotid body function and gene expression. Global gene profile analysis in cell cultures suggests that certain genes are selectively affected by intermittent
hypoxia, some upregulated and some downregulated. It is suggested that, in intact animals, coordinated gene regulation of gene expression might be critical for eliciting phenotypic changes in the cardiorespiratory systems in response to intermittent
hypoxia. It is hoped that future studies will unravel new mechanisms that are unique to intermittent
hypoxia that may lead to a better understanding of the changes in the cardiorespiratory systems and new
therapies for diseases associated with chronic recurrent episodes of
hypoxia.