Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fphys.2017.00452 http://hdl.handle.net/11449/162935 |
Resumo: | 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 preBotzinger Complex (preBotC, 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-beta-synthase (CBS) in the CNS, acts specifically within the preBotC 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, 0.1-1.0mM) to rhythmic brainstem spinal cord (BSSC) and medullary slice preparations from newborn rats, or local application of AOAA into the preBotC (slices only) caused a dose-dependent decrease in burst frequency. Unilateral injection of AOAA into the preBotC 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% O-2, 5 min) increase in ventilatory output, but enhanced the secondary hypoxic respiratory depression. These data suggest that the preBotC 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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Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfidecontrol of breathinghypoxiaH2Scystathionine-beta-synthaseAOAApreBotzinger ComplexHydrogen 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 preBotzinger Complex (preBotC, 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-beta-synthase (CBS) in the CNS, acts specifically within the preBotC 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, 0.1-1.0mM) to rhythmic brainstem spinal cord (BSSC) and medullary slice preparations from newborn rats, or local application of AOAA into the preBotC (slices only) caused a dose-dependent decrease in burst frequency. Unilateral injection of AOAA into the preBotC 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% O-2, 5 min) increase in ventilatory output, but enhanced the secondary hypoxic respiratory depression. These data suggest that the preBotC inspiratory network receives tonic excitatory modulation from the CBS-H2S system, and that endogenous H2S attenuates the secondary hypoxic respiratory depression.CIHRNSERCCFIWCHRIFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Alberta, Women & Childrens Hlth Res Inst, Neurosci & Mental Hlth Inst, Dept Physiol,Fac Med & Dent, Edmonton, AB, CanadaSao Paulo State Univ, Dept Morphol & Anim Physiol, Jaboticabal, BrazilUniv Fed Piaui, Dept Biophys & Physiol, Teresina, BrazilUniv Sao Paulo, Fac Dent Ribeirao Preto, Dept Physiol, Ribeirao Preto, BrazilHosp Sick Children, Peter Gilgan Ctr Res & Learning, Neurosci & Mental Hlth, Toronto, ON, CanadaSao Paulo State Univ, Dept Morphol & Anim Physiol, Jaboticabal, BrazilCIHR: 53085CIHR: 130306NSERC: 402532NSERC: 434543FAPESP: FAPESP-2012/02413-8FAPESP: 2014/12951-2: FAPESP 2013/17606-9Frontiers Media SaUniv AlbertaUniversidade Estadual Paulista (Unesp)Univ Fed PiauiUniversidade de São Paulo (USP)Hosp Sick ChildrenSilva, Glauber S. F. da [UNESP]Sabino, Joao P. J.Rajani, VishaalAlvares, Tucaaue S.Pagliardini, SilviaBranco, Luiz G. S.Funk, Gregory D.2018-11-26T17:35:00Z2018-11-26T17:35:00Z2017-06-30info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://dx.doi.org/10.3389/fphys.2017.00452Frontiers In Physiology. Lausanne: Frontiers Media Sa, v. 8, 13 p., 2017.1664-042Xhttp://hdl.handle.net/11449/16293510.3389/fphys.2017.00452WOS:000404483000001WOS000404483000001.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers In Physiologyinfo:eu-repo/semantics/openAccess2023-12-01T06:15:15Zoai:repositorio.unesp.br:11449/162935Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-01T06:15:15Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide |
title |
Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide |
spellingShingle |
Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide Silva, Glauber S. F. da [UNESP] control of breathing hypoxia H2S cystathionine-beta-synthase AOAA preBotzinger Complex |
title_short |
Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide |
title_full |
Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide |
title_fullStr |
Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide |
title_full_unstemmed |
Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide |
title_sort |
Excitatory Modulation of the preBotzinger Complex Inspiratory Rhythm Generating Network by Endogenous Hydrogen Sulfide |
author |
Silva, Glauber S. F. da [UNESP] |
author_facet |
Silva, Glauber S. F. da [UNESP] Sabino, Joao P. J. Rajani, Vishaal Alvares, Tucaaue S. Pagliardini, Silvia Branco, Luiz G. S. Funk, Gregory D. |
author_role |
author |
author2 |
Sabino, Joao P. J. Rajani, Vishaal Alvares, Tucaaue S. Pagliardini, Silvia Branco, Luiz G. S. Funk, Gregory D. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Univ Alberta Universidade Estadual Paulista (Unesp) Univ Fed Piaui Universidade de São Paulo (USP) Hosp Sick Children |
dc.contributor.author.fl_str_mv |
Silva, Glauber S. F. da [UNESP] Sabino, Joao P. J. Rajani, Vishaal Alvares, Tucaaue S. Pagliardini, Silvia Branco, Luiz G. S. Funk, Gregory D. |
dc.subject.por.fl_str_mv |
control of breathing hypoxia H2S cystathionine-beta-synthase AOAA preBotzinger Complex |
topic |
control of breathing hypoxia H2S cystathionine-beta-synthase AOAA preBotzinger Complex |
description |
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 preBotzinger Complex (preBotC, 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-beta-synthase (CBS) in the CNS, acts specifically within the preBotC 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, 0.1-1.0mM) to rhythmic brainstem spinal cord (BSSC) and medullary slice preparations from newborn rats, or local application of AOAA into the preBotC (slices only) caused a dose-dependent decrease in burst frequency. Unilateral injection of AOAA into the preBotC 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% O-2, 5 min) increase in ventilatory output, but enhanced the secondary hypoxic respiratory depression. These data suggest that the preBotC inspiratory network receives tonic excitatory modulation from the CBS-H2S system, and that endogenous H2S attenuates the secondary hypoxic respiratory depression. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-06-30 2018-11-26T17:35:00Z 2018-11-26T17:35:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fphys.2017.00452 Frontiers In Physiology. Lausanne: Frontiers Media Sa, v. 8, 13 p., 2017. 1664-042X http://hdl.handle.net/11449/162935 10.3389/fphys.2017.00452 WOS:000404483000001 WOS000404483000001.pdf |
url |
http://dx.doi.org/10.3389/fphys.2017.00452 http://hdl.handle.net/11449/162935 |
identifier_str_mv |
Frontiers In Physiology. Lausanne: Frontiers Media Sa, v. 8, 13 p., 2017. 1664-042X 10.3389/fphys.2017.00452 WOS:000404483000001 WOS000404483000001.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers In Physiology |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
13 application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media Sa |
publisher.none.fl_str_mv |
Frontiers Media Sa |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1799965133025312768 |