Systemic, cellular and molecular analysis of chemoreflex-mediated sympathoexcitation by chronic intermittent hypoxia.
Patients with recurrent apnoeas exhibit autonomic abnormalities manifested as persistent increase in sympathetic nerve activity (SNA). Several studies suggest that chronic intermittent hypoxia (CIH) resulting from recurrent apnoeas is a major stimulus for evoking autonomic morbidity. Although it has been proposed that CIH, by way of activating the chemoreceptor reflex, leads to sympathetic excitation, the underlying mechanisms are incompletely understood. Studies on experimental models have provided new insights into the mechanisms associated with CIH-evoked sympathoexcitation. The purpose of this article is to highlight recent information on systemic, cellular and molecular analysis of the effects of CIH on chemoreceptor-mediated sympathoexcitation. Chronic intermittent hypoxia exerts two major effects on the chemoreceptor reflex: (a) augmentation of the carotid body and sympathetic effector responses to acute hypoxia; and (b) induction of long-lasting activation of both the sensor and the effector that persists several hours after termination of CIH. Available evidence indicates that CIH may facilitate processing of chemoreceptor afferent information at the central nervous system. Recent studies suggest that reactive oxygen species-mediated signalling is a major cellular mechanism, and transcriptional activation by hypoxia-inducible factor-1 is one of the critical molecular mechanisms underlying chemoreceptor-mediated sympathoexcitation by CIH.
Prabhakar
Nanduri R
NR
Department of Physiology & Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44109, USA. nrp@case.edu. nrp@case.edu
Dick
Thomas E
TE
Nanduri
Jayasri
J
Kumar
Ganesh K
GK
D000818:Animals; D002628:Chemoreceptor Cells / Q000503:physiopathology*; D002908:Chronic Disease; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012018:Reflex; D020181:Sleep Apnea, Obstructive / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species