title: Mechanisms of maladaptive responses of peripheral chemoreceptors to intermittent hypoxia in sleep-disordered breathing.
abstract: Peripheral chemoreceptors in the carotid body play important roles in the transduction of chemical stimuli in the arterial blood to the central for eliciting the chemoreflex, which mediates the ventilatory and circulatory responses to hypoxia. The activity of carotid chemoreceptor is modulated and significantly contributes to the ventilatory acclimatization at high altitude. In addition, the carotid chemoreceptor activity is augmented in patients with sleep-disordered breathing, notably in central or obstructive sleep apnea, and also in experimental animals. Thus, the carotid body functions to maintain the oxygen homeostasis, whereas anomalous carotid chemoreceptor activities could be both adaptive and pathogenic in sleep apnea. This review aims to summarize the cellular and molecular mechanisms that could mediate the augmented chemoreceptor activity induced by intermittent hypoxia. Our recent findings suggest a pathogenic role of inflammation mediated by an upregulation of renin-angiotensin system in the carotid body in the over-activity of the chemoreflex. These locally regulated mechanisms are proposed to be a significant part of the hypoxia-mediated maladaptive changes of the carotid body function, which could play a role in the pathophysiology of sleep apnea.
authors.affiliation: Department of Physiology; Department of Anatomy; Research Centre of Heart, Brain, Hormone & Healthy Aging, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China. fungml@hku.hk.
authors.forename: Man Lung
authors.initials: ML
authors.lastname: Fung
authors.forename: George Lim
authors.initials: GL
authors.lastname: Tipoe
authors.forename: Po Sing
authors.initials: PS
authors.lastname: Leung
mesh_terms: D000064:Acclimatization; D000818:Animals; D002344:Carotid Body / Q000166:cytology; D002628:Chemoreceptor Cells / Q000473:pathology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D012084:Renin-Angiotensin System; D012891:Sleep Apnea Syndromes / Q000503:physiopathology*