Reactive oxygen radicals and gaseous transmitters in carotid body activation by intermittent hypoxia
Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has...
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Veröffentlicht in: | Cell and tissue research 2018-05, Vol.372 (2), p.427-431 |
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Sprache: | eng |
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Zusammenfassung: | Sleep apnea is a prevalent respiratory disease characterized by periodic cessation of breathing during sleep causing intermittent hypoxia (IH). Sleep apnea patients and rodents exposed to IH exhibit elevated sympathetic nerve activity and hypertension. A heightened carotid body (CB) chemoreflex has been implicated in causing autonomic abnormalities in IH-treated rodents and in sleep apnea patients. The purpose of this article is to review the emerging evidence showing that interactions between reactive oxygen species (ROS) and gaseous transmitters as a mechanism cause hyperactive CB by IH. Rodents treated with IH exhibit markedly elevated ROS in the CB, which is due to transcriptional upregulation of pro-oxidant enzymes by hypoxia-inducible factor (HIF)-1 and insufficient transcriptional regulation of anti-oxidant enzymes by HIF-2. ROS, in turn, increases cystathionine γ-lyase (CSE)-dependent H
2
S production in the CB. Blockade of H
2
S synthesis prevents IH-evoked CB activation. However, the effects of ROS on H
2
S production are not due to direct effects on CSE enzyme activity but rather due to inactivation of heme oxygenase-2 (HO-2), a carbon monoxide (CO) producing enzyme. CO inhibits H
2
S production through inactivation of CSE by PKG-dependent phosphorylation. During IH, reduced CO production resulting from inactivation of HO-2 by ROS releases the inhibition of CO on CSE thereby increasing H
2
S. Inhibiting H
2
S synthesis prevented IH-evoked sympathetic activation and hypertension. |
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ISSN: | 0302-766X 1432-0878 |
DOI: | 10.1007/s00441-018-2807-0 |