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Complementary roles of gasotransmitters CO and H2S in sleep apnea.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2017 Feb 07; Vol. 114 (6), pp. 1413-1418. Date of Electronic Publication: 2017 Jan 23. - Publication Year :
- 2017
-
Abstract
- Sleep apnea, which is the periodic cessation of breathing during sleep, is a major health problem affecting over 10 million people in the United States and is associated with several sequelae, including hypertension and stroke. Clinical studies suggest that abnormal carotid body (CB) activity may be a driver of sleep apnea. Because gaseous molecules are important determinants of CB activity, aberrations in their signaling could lead to sleep apnea. Here, we report that mice deficient in heme oxygenase-2 (HO-2), which generates the gaseous molecule carbon monoxide (CO), exhibit sleep apnea characterized by high apnea and hypopnea indices during rapid eye movement (REM) sleep. Similar high apnea and hypopnea indices were also noted in prehypertensive spontaneously hypertensive (SH) rats, which are known to exhibit CB hyperactivity. We identified the gaseous molecule hydrogen sulfide (H <subscript>2</subscript> S) as the major effector molecule driving apneas. Genetic ablation of the H <subscript>2</subscript> S-synthesizing enzyme cystathionine-γ-lyase (CSE) normalized breathing in HO-2 <superscript>-/-</superscript> mice. Pharmacologic inhibition of CSE with l-propargyl glycine prevented apneas in both HO-2 <superscript>-/-</superscript> mice and SH rats. These observations demonstrate that dysregulated CO and H <subscript>2</subscript> S signaling in the CB leads to apneas and suggest that CSE inhibition may be a useful therapeutic intervention for preventing CB-driven sleep apnea.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Animals
Carotid Body metabolism
Carotid Body physiopathology
Cystathionine gamma-Lyase genetics
Cystathionine gamma-Lyase metabolism
Female
Heme Oxygenase (Decyclizing) genetics
Heme Oxygenase (Decyclizing) metabolism
Male
Mice, Inbred C57BL
Mice, Knockout
Rats, Inbred SHR
Rats, Inbred WKY
Respiration genetics
Sleep Apnea Syndromes genetics
Sleep Apnea Syndromes physiopathology
Carbon Monoxide metabolism
Gasotransmitters metabolism
Hydrogen Sulfide metabolism
Sleep Apnea Syndromes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 114
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 28115703
- Full Text :
- https://doi.org/10.1073/pnas.1620717114