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
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Carreau A, El Hafny-Rahbi B, Matejuk A et al (2011) Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia. J Cell Mol Med 15:1239–1253
Gardner PR (2002) Aconitase sensitive target and measure of superoxide. Methods Enzymol 349:9–23
Kumar GK, Rai V, Sharma SD et al (2006) Chronic intermittent hypoxia induces hypoxia-evoked catecholamine efflux in adult rat adrenal medulla via oxidative stress. J Physiol 575:229–239
Kuri BA, Khan SA, Chan SA et al (2007) Increased secretory capacity of mouse adrenal chromaffin cells by chronic intermittent hypoxia: involvement of protein kinase C. J Physiol 584:313–319
Peng YJ, Yuan G, Khan S et al (2014) Regulation of hypoxia-inducible factor-α isoforms and redox state by carotid body neural activity in rats. J Physiol 592:3841–3858
Prabhakar NR, Kumar GK, Nanduri J et al (2007) ROS signaling in systemic and cellular responses to chronic intermittent hypoxia. Antioxid Redox Signal 9:1397–1403
Verna A, Roumy M, Leitner LM (1975) Loss of chemoreceptive properties of the rabbit carotid body after destruction of the glomus cells. Brain Res 100:13–23
Acknowledgement
This research was supported by grant P01-HL-90554 from the National Institute of Health, Heart, Lung and Blood Institute.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Kumar, G.K., Peng, YJ., Nanduri, J., Prabhakar, N.R. (2015). Carotid Body Chemoreflex Mediates Intermittent Hypoxia-Induced Oxidative Stress in the Adrenal Medulla. In: Peers, C., Kumar, P., Wyatt, C., Gauda, E., Nurse, C., Prabhakar, N. (eds) Arterial Chemoreceptors in Physiology and Pathophysiology. Advances in Experimental Medicine and Biology, vol 860. Springer, Cham. https://doi.org/10.1007/978-3-319-18440-1_21
Download citation
DOI: https://doi.org/10.1007/978-3-319-18440-1_21
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-18439-5
Online ISBN: 978-3-319-18440-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)