Endogenous hydrogen sulfide is involved in regulation of respiration in medullary slice of neonatal rats

Hu, Haiyan; Shi, Yuanyuan; Chen, Q.; Yang, Wenxing; Zhou, Hua; Chen, L.; Tang, Yuhong; Zheng, Yu

doi:10.1016/j.neuroscience.2008.08.025

Cited by 42 publications

(26 citation statements)

References 31 publications

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“…H 2 S increases discharge frequency from the pre-Bötzinger (pB) dorsal inspiratory respiratory group, and it may initially produce transient inhibition of the pB by stimulating the nearby parafacial respiratory group (pFRG) (19,61). Discharge frequency of hypoglossal rootlets in medullary slices of female neonatal Sprague-Dawley rats is transiently decreased and then increased as H 2 S is increased from 100 to 300 lM and then decreased at 400 lM H 2 S (61).…”

Section: H 2 S Mediation Of Central Respiratory Centersmentioning

confidence: 99%

Hydrogen sulfide as an oxygen sensor

Olson

2013

Clinical Chemistry and Laboratory Medicine

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Significance: Although oxygen (O 2 )-sensing cells and tissues have been known for decades, the identity of the O 2 -sensing mechanism has remained elusive. Evidence is accumulating that O 2 -dependent metabolism of hydrogen sulfide (H 2 S) is this enigmatic O 2 sensor. Recent Advances: The elucidation of biochemical pathways involved in H 2 S synthesis and metabolism have shown that reciprocal H 2 S/O 2 interactions have been inexorably linked throughout eukaryotic evolution; there are multiple foci by which O 2 controls H 2 S inactivation, and the effects of H 2 S on downstream signaling events are consistent with those activated by hypoxia. H 2 S-mediated O 2 sensing has been demonstrated in a variety of O 2 -sensing tissues in vertebrate cardiovascular and respiratory systems, including smooth muscle in systemic and respiratory blood vessels and airways, carotid body, adrenal medulla, and other peripheral as well as central chemoreceptors. Critical Issues: Information is now needed on the intracellular location and stoichometry of these signaling processes and how and which downstream effectors are activated by H 2 S and its metabolites. Future Directions: Development of specific inhibitors of H 2 S metabolism and effector activation as well as cellular organelle-targeted compounds that release H 2 S in a timeor environmentally controlled way will not only enhance our understanding of this signaling process but also provide direction for future therapeutic applications. Antioxid. Redox Signal. 22, 377-397.

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Section: H 2 S Mediation Of Central Respiratory Centersmentioning

confidence: 99%

Hydrogen sulfide as an oxygen sensor

Olson

2013

Clinical Chemistry and Laboratory Medicine

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“…Application of exogenous cysteine (CYS, a metabolic precursor of H 2 S) to thick brainstem slices in vitro (Hu et al, 2008; Pan et al, 2010, 2011) or in vivo (Li et al, 2014) evokes the same range of responses, indicating that the network can be modulated by endogenously generated H 2 S. These data are not, however, evidence of physiological modulation. The only evidence of a physiological role for H 2 S signaling in respiratory control is the inhibition of ventilation following inhibition of H 2 S synthesis throughout the brainstem in vitro and in vivo (Hu et al, 2008; Li et al, 2014), but not all studies support a role for endogenous H 2 S in baseline respiratory activity (Pan et al, 2011; da Silva et al, 2014; Li et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…The brainstem respiratory network is sensitive to exogenous H 2 S, since application of donors in vitro and in vivo evoke a biphasic ventilatory response comprising an initial inhibition followed by excitation (Hu et al, 2008; Chen et al, 2013a,b; Li et al, 2014), or an excitation alone (Pan et al, 2011; Chen et al, 2013b). Application of exogenous cysteine (CYS, a metabolic precursor of H 2 S) to thick brainstem slices in vitro (Hu et al, 2008; Pan et al, 2010, 2011) or in vivo (Li et al, 2014) evokes the same range of responses, indicating that the network can be modulated by endogenously generated H 2 S. These data are not, however, evidence of physiological modulation.…”

Section: Introductionmentioning

confidence: 99%

Excitatory Modulation of the preBötzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide

et al. 2017

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Hydrogen Sulfide (H2S) is one of three gasotransmitters that modulate excitability in the CNS. Global application of H2S donors or inhibitors of H2S synthesis to the respiratory network has suggested that inspiratory rhythm is modulated by exogenous and endogenous H2S. However, effects have been variable, which may reflect that the RTN/pFRG (retrotrapezoid nucleus, parafacial respiratory group) and the preBötzinger Complex (preBötC, critical for inspiratory rhythm generation) are differentially modulated by exogenous H2S. Importantly, site-specific modulation of respiratory nuclei by H2S means that targeted, rather than global, manipulation of respiratory nuclei is required to understand the role of H2S signaling in respiratory control. Thus, our aim was to test whether endogenous H2S, which is produced by cystathionine-β-synthase (CBS) in the CNS, acts specifically within the preBötC to modulate inspiratory activity under basal (in vitro/in vivo) and hypoxic conditions (in vivo). Inhibition of endogenous H2S production by bath application of the CBS inhibitor, aminooxyacetic acid (AOAA, 0.1–1.0 mM) to rhythmic brainstem spinal cord (BSSC) and medullary slice preparations from newborn rats, or local application of AOAA into the preBötC (slices only) caused a dose-dependent decrease in burst frequency. Unilateral injection of AOAA into the preBötC of anesthetized, paralyzed adult rats decreased basal inspiratory burst frequency, amplitude and ventilatory output. AOAA in vivo did not affect the initial hypoxia-induced (10% O2, 5 min) increase in ventilatory output, but enhanced the secondary hypoxic respiratory depression. These data suggest that the preBötC inspiratory network receives tonic excitatory modulation from the CBS-H2S system, and that endogenous H2S attenuates the secondary hypoxic respiratory depression.

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“…CBS is found in abundance in the brain [22] , whereas little of CSE is primarily found peripherally with limited expression in the central nervous system [23] . Inhibition and activation of CBS have been found to decrease and increase the frequency of rhythmic meduallary respiratory activity, respectively [5] . At rest, no differences were found amongst the HSSI agents compared to saline in the number of animals expressing one or more apneas, but injection of the CBS inhibitor HA (300 mol/kg) resulted in a trend towards increased stability.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a blunted hypoxic responsiveness occurs in vivo in Kunming mice administered HA and AOAA [3] as well as mice with knockout mutations for CSE [4] . In addition, the discharge rate of rhythmic respiratory activity in isolated medullary sections from neonatal rats will decrease in response to HA and increase with administration of the CBS substrate cysteine, suggesting a potential role for H 2 S signaling in central respiratory control [5] . These observations imply that the pathways influencing H 2 S synthesis and activity could be targets of drug therapy for disorders of ventilatory control including unstable breathing disorders seen in a variety of medical and neurologic conditions [6] .…”

Section: Introductionmentioning

confidence: 99%

Effects of Hydrogen Sulfide Synthesis Inhibitors on Posthypoxic Ventilatory Behavior in the C57BL/6J Mouse

et al. 2011

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Background: H2S synthesis inhibitors (HSSI) have been shown to impact respiratory control. For instance, the HSSI hydroxylamine (HA) decreases the respiratory discharge rate from isolated medullary sections, and HA in addition to other HSSIs propargylglycine and amino-oxyacetic acid (AOAA) have been found to reduce hypoxic responsiveness. Objectives: The aim of this study was to determine if administration of HSSIs could improve respiratory stability in an intact organism prone to recurrent central apneas. Methods: Saline and HSSI compounds were administered to C57BL/6J mice (n = 24), a strain predisposed to recurrent central apneas, prior to measurement of hypoxic and posthypoxic ventilatory behavior. Results: Administration of HA and AOAA resulted in a significantly smaller percentage of animals expressing one or more apneas during reoxygenation compared to saline control, and animals given AOAA demonstrated a smaller coefficient of variation for frequency during reoxygenation, a marker suggesting greater respiratory stability. This occurred despite varying effects of the three HSSI compounds on hypoxic ventilatory response. Conclusions: Instability and pause expression are improved by targeting H2S synthesis, an effect not predicted by effects on hypoxic responsiveness.

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Endogenous hydrogen sulfide is involved in regulation of respiration in medullary slice of neonatal rats

Cited by 42 publications

References 31 publications

Hydrogen sulfide as an oxygen sensor

Hydrogen sulfide as an oxygen sensor

Excitatory Modulation of the preBötzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide

Effects of Hydrogen Sulfide Synthesis Inhibitors on Posthypoxic Ventilatory Behavior in the C57BL/6J Mouse

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