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Carotid Body Chemoreflex Mediates Intermittent Hypoxia-Induced Oxidative Stress in the Adrenal Medulla

  • Ganesh K. KumarEmail author
  • Ying-Jie Peng
  • Jayasri Nanduri
  • Nanduri R. Prabhakar
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 860)

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 O2 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.

Keywords

Reactive oxygen species Sleep disordered breathing Hypoxia-inducible factors Carotid body ablation Pro-oxidant and anti-oxidant 

Notes

Acknowledgement

This research was supported by grant P01-HL-90554 from the National Institute of Health, Heart, Lung and Blood Institute.

References

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Ganesh K. Kumar
    • 1
    Email author
  • Ying-Jie Peng
    • 1
  • Jayasri Nanduri
    • 2
  • Nanduri R. Prabhakar
    • 3
  1. 1.Institute for Integrative Physiology & Center for Systems Biology for O2 SensingThe University of ChicagoChicagoUSA
  2. 2.Biological Science DivisionInstitute for Integrative PhysiologyChicagoUSA
  3. 3.Biological Science Division, Institute for Integrative Physiology and Center for Systems Biology of O(2) SensingUniversity of ChicagoChicagoUSA

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