Therapeutic Targeting of the Carotid Body for Treating Sleep Apnea in a Pre-clinical Mouse Model

  • Ying-Jie Peng
  • Xiuli Zhang
  • Jayasri Nanduri
  • Nanduri R. PrabhakarEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1071)


Sleep apnea with periodic cessation of breathing during sleep is a highly prevalent respiratory disorder affecting an estimated 10% of adults. Patients with sleep apnea exhibit several co-morbidities including hypertension, stroke, disrupted sleep, and neurocognitive and metabolic complications. Emerging evidence suggests that a hyperactive carotid body (CB) chemo reflex is an important driver of apneas in sleep apnea patients. Gasotransmitters carbon monoxide (CO) and hydrogen sulfide (H2S) play important roles in oxygen sensing by the CB. We tested the hypothesis that an augmented CB chemo reflex stemming from disrupted CO-H2S signaling may lead to sleep apnea. This possibility was tested in mice deficient in hemeoxygenase-2 (HO-2), an enzyme involved in CO synthesis, which were shown to exhibit hyperactive CB activity due to high H2S levels. We found that HO-2−/− mice exhibit a high incidence of apneas during sleep compared to wild type mice. Blocking the CB hyperactivity with L-propargylglycine, an inhibitor of cystathionine-γ-lyase (CSE), which catalyzes H2S synthesis, prevented apneas in HO-2−/− mice. These findings suggest that targeting CB with inhibitors of CSE might be a novel therapeutic strategy for preventing sleep apnea.


Hemeoxygenase-2 Carbon monoxide Cystathionine-γ-lyase Hydrogen sulfide Obstructive Central sleep apnea 



This work was supported by National Institutes of Health grants P01-HL-90554 and UH2-HL-123610.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Ying-Jie Peng
    • 1
  • Xiuli Zhang
    • 1
  • Jayasri Nanduri
    • 1
  • Nanduri R. Prabhakar
    • 1
    Email author
  1. 1.Institute for Integrative Physiology and Center for Systems Biology of Oxygen Sensing, Biological Sciences DivisionUniversity of ChicagoChicagoUSA

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