H2S Contributes to Carotid Body Response to Hypoxia but Not Anoxia

Abstract

We previously reported that cystathionine‐γ‐lyase (CSE)‐derived H2S mediates carotid body (CB) response to hypoxia (Hx) (Peng et al., PNAS, 2010). A recent study showed that CB Type I cell responses to anoxia (Ax) were unaffected by CSE inhibitors (Kim et al. Respir Physiology, 2015). We re‐examined the role of CSE‐derived H2S in CB sensory and Type I cell responses to Hx and Ax in adult Sprague‐Dawley rats, wild‐type and CSE knockout (KO) mice. Hx (pO2=37± 3mmHg) produced robust sensory excitation, and increased H2S levels in the CB; whereas Ax (pO2 =5±4 mmHg) produced only a weak sensory excitation and had no effect on H2S levels. Ax evoked a robust [Ca2+]i response of Type I cells as compared to hypoxia. CSE inhibitor DL‐propargylglycine (DL‐PAG, 50μM) inhibited Hx but not Ax‐evoked sensory and Type I responses. Higher concentration (300μM) of DL‐PAG alone, or in combination with aminooxyacetic acid (300μM), non‐selectively blocked [Ca2+]i responses of Type I cells to Ax and decreased cell viability. CB sensory excitation and [Ca2+]i elevation in Type I cells were unaffected in CSE null mice as compared to wild‐type (Wt) mice. Breathing stimulation by Hx was absent in CSE KO mice, whereas depressed breathing by Ax was unaffected. These observations suggest that CSE‐derived H2S contributes to carotid body response to “physiologically” relevant hypoxia but not to anoxia.Support or Funding InformationSupported by National Institutes of Health grants P01‐HL‐90554This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.