title: Carotid Body Chemoreflex Mediates Intermittent Hypoxia-Induced Oxidative Stress in the Adrenal Medulla.
abstract: Intermittent hypoxia (IH) increases reactive oxygen species generation resulting in oxidative stress in the adrenal medulla (AM), a major end-organ of the sympathetic nervous system which facilitates catecholamine secretion by hypoxia. Here, we show that carotid body chemoreflex contributes to IH-induced oxidative stress in the AM. Carotid bodies were ablated by cryocoagulation of glomus cells, the putative O(2) sensing cells. Carotid body ablated (CBA) and control rats were exposed to IH and the redox state of the AM was assessed biochemically. We found that IH raised reactive oxygen species levels along with an increase in NADPH oxidase (Nox), a pro-oxidant enzyme and a decrease in superoxide dismutase-2 (SOD2), an anti-oxidant enzyme. Further, IH increased hypoxia-inducible factor (HIF)-1α, whereas decreased HIF-2α, the transcriptional regulator of Nox and SOD-2, respectively. These IH-induced changes in the AM were absent in CBA rats. Moreover, IH increased splanchnic nerve activity and facilitated hypoxia-evoked catecholamine efflux from the AM and CBA prevented these effects. These findings suggest that IH-induced oxidative stress and catecholamine efflux in the AM occurs via carotid body chemoreflex involving HIF α isoform mediated imbalance in pro-, and anti-oxidant enzymes.
authors: Institute for Integrative Physiology & Center for Systems Biology for O2 Sensing, The University of Chicago, Chicago, IL, 60637, USA, gkumar@bsd.uchicago.edu.
authors: Ganesh K
authors: GK
authors: Kumar
authors: Ying-Jie
authors: YJ
authors: Peng
authors: Jayasri
authors: J
authors: Nanduri
authors: Nanduri R
authors: NR
authors: Prabhakar
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002344:Carotid Body / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000502:physiology*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit