Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/54198 http://dx.doi.org/10.14814/phy2.13536 |
Resumo: | Obstructive sleep apnea (OSA) is the most common respiratory disturbance of sleep and is closely associated to cardiovascular diseases. In humans, apnea increases respiratory effort and elevates muscle sympathetic nerve activity (SNA), but the primary stimulus for the SNA activation has not been identified. We recently developed a model of apnea in rodents using acute airway obstruction. In this study, we employed this model to test whether the elevation in SNA was mediated by hypoxia, carotid chemoreceptors, or neurotransmission in the nucleus tractus solitarius (NTS). In anesthetized, male Sprague-Dawley rats, airway obstruction (20s) increased phrenic nerve activity (PNA), arterial blood pressure (ABP), and lumbar, renal, and splanchnic SNA. The changes in SNA were similar across all three sympathetic nerves. Inactivation of chemoreceptors by hyperoxia (100% O-2) or surgical denervation of carotid chemoreceptors attenuated, but did not eliminate, the changes in SNA and ABP produced by airway obstruction. To interrupt afferent information from carotid chemoreceptor and extracarotid afferents to the hindbrain, airway obstruction was performed before and after NTS microinjection of the GABA(A) agonist muscimol or a cocktail of NMDA and non-NMDA antagonists. Inhibition of NTS neurons or blockade of glutamatergic receptors attenuated the increase in lumbar SNA, splanchnic SNA, renal SNA, and PNA. Collectively, these findings suggest that PNA and SNA responses induced by airway obstruction depend, in part, on chemoreceptors afferents and glutamatergic neurotransmission in the NTS. |
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Ferreira, Caroline B. [UNIFESP]Cravo, Sergio L. [UNIFESP]Stocker, Sean D.2020-07-08T13:09:46Z2020-07-08T13:09:46Z2018Physiological Reports. Hoboken, v. 6, n. 3, p. -, 2018.2051-817Xhttps://repositorio.unifesp.br/handle/11600/54198http://dx.doi.org/10.14814/phy2.13536WOS000425110700002.pdf10.14814/phy2.13536WOS:000425110700002Obstructive sleep apnea (OSA) is the most common respiratory disturbance of sleep and is closely associated to cardiovascular diseases. In humans, apnea increases respiratory effort and elevates muscle sympathetic nerve activity (SNA), but the primary stimulus for the SNA activation has not been identified. We recently developed a model of apnea in rodents using acute airway obstruction. In this study, we employed this model to test whether the elevation in SNA was mediated by hypoxia, carotid chemoreceptors, or neurotransmission in the nucleus tractus solitarius (NTS). In anesthetized, male Sprague-Dawley rats, airway obstruction (20s) increased phrenic nerve activity (PNA), arterial blood pressure (ABP), and lumbar, renal, and splanchnic SNA. The changes in SNA were similar across all three sympathetic nerves. Inactivation of chemoreceptors by hyperoxia (100% O-2) or surgical denervation of carotid chemoreceptors attenuated, but did not eliminate, the changes in SNA and ABP produced by airway obstruction. To interrupt afferent information from carotid chemoreceptor and extracarotid afferents to the hindbrain, airway obstruction was performed before and after NTS microinjection of the GABA(A) agonist muscimol or a cocktail of NMDA and non-NMDA antagonists. Inhibition of NTS neurons or blockade of glutamatergic receptors attenuated the increase in lumbar SNA, splanchnic SNA, renal SNA, and PNA. Collectively, these findings suggest that PNA and SNA responses induced by airway obstruction depend, in part, on chemoreceptors afferents and glutamatergic neurotransmission in the NTS.National Heart, Lung, and Blood Institute GrantAmerican Heart Association Established Investigator AwardCoordination of Training of Higher Education Graduate Foundation (CAPES)National Council for Scientific and Technological Development (CNPq)Univ Fed Sao Paulo, Dept Physiol, Sao Paulo, SP, BrazilUniv Pittsburgh, Sch Med, Dept Med, Div Renal Electrolyte, Pittsburgh, PA 15213 USAUniv Pittsburgh, Sch Med, Hypertens Ctr, Pittsburgh, PA USAUniv Fed Sao Paulo, Dept Physiol, Sao Paulo, SP, BrazilNational Heart, Lung, and Blood Institute Grant: R01 HL113270Web of Science-engWileyPhysiological ReportsApneacarotid chemoreceptorsNTSsympathetic nerve activityAirway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmissioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleHoboken63info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000425110700002.pdfapplication/pdf1364946${dspace.ui.url}/bitstream/11600/54198/1/WOS000425110700002.pdf07870f54a0183e52b787c33db2150781MD51open accessTEXTWOS000425110700002.pdf.txtWOS000425110700002.pdf.txtExtracted texttext/plain45574${dspace.ui.url}/bitstream/11600/54198/2/WOS000425110700002.pdf.txt9272295601ecc3281ef58c24e035ba82MD52open accessTHUMBNAILWOS000425110700002.pdf.jpgWOS000425110700002.pdf.jpgIM Thumbnailimage/jpeg6941${dspace.ui.url}/bitstream/11600/54198/4/WOS000425110700002.pdf.jpg556a3023214be72316d1ecafe6a3e53dMD54open access11600/541982022-08-01 07:47:03.875open accessoai:repositorio.unifesp.br:11600/54198Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-08-01T10:47:03Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission |
title |
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission |
spellingShingle |
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission Ferreira, Caroline B. [UNIFESP] Apnea carotid chemoreceptors NTS sympathetic nerve activity |
title_short |
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission |
title_full |
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission |
title_fullStr |
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission |
title_full_unstemmed |
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission |
title_sort |
Airway obstruction produces widespread sympathoexcitation: role of hypoxia, carotid chemoreceptors, and NTS neurotransmission |
author |
Ferreira, Caroline B. [UNIFESP] |
author_facet |
Ferreira, Caroline B. [UNIFESP] Cravo, Sergio L. [UNIFESP] Stocker, Sean D. |
author_role |
author |
author2 |
Cravo, Sergio L. [UNIFESP] Stocker, Sean D. |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Ferreira, Caroline B. [UNIFESP] Cravo, Sergio L. [UNIFESP] Stocker, Sean D. |
dc.subject.eng.fl_str_mv |
Apnea carotid chemoreceptors NTS sympathetic nerve activity |
topic |
Apnea carotid chemoreceptors NTS sympathetic nerve activity |
description |
Obstructive sleep apnea (OSA) is the most common respiratory disturbance of sleep and is closely associated to cardiovascular diseases. In humans, apnea increases respiratory effort and elevates muscle sympathetic nerve activity (SNA), but the primary stimulus for the SNA activation has not been identified. We recently developed a model of apnea in rodents using acute airway obstruction. In this study, we employed this model to test whether the elevation in SNA was mediated by hypoxia, carotid chemoreceptors, or neurotransmission in the nucleus tractus solitarius (NTS). In anesthetized, male Sprague-Dawley rats, airway obstruction (20s) increased phrenic nerve activity (PNA), arterial blood pressure (ABP), and lumbar, renal, and splanchnic SNA. The changes in SNA were similar across all three sympathetic nerves. Inactivation of chemoreceptors by hyperoxia (100% O-2) or surgical denervation of carotid chemoreceptors attenuated, but did not eliminate, the changes in SNA and ABP produced by airway obstruction. To interrupt afferent information from carotid chemoreceptor and extracarotid afferents to the hindbrain, airway obstruction was performed before and after NTS microinjection of the GABA(A) agonist muscimol or a cocktail of NMDA and non-NMDA antagonists. Inhibition of NTS neurons or blockade of glutamatergic receptors attenuated the increase in lumbar SNA, splanchnic SNA, renal SNA, and PNA. Collectively, these findings suggest that PNA and SNA responses induced by airway obstruction depend, in part, on chemoreceptors afferents and glutamatergic neurotransmission in the NTS. |
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2018 |
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2018 |
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2020-07-08T13:09:46Z |
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2020-07-08T13:09:46Z |
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dc.identifier.citation.fl_str_mv |
Physiological Reports. Hoboken, v. 6, n. 3, p. -, 2018. |
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https://repositorio.unifesp.br/handle/11600/54198 http://dx.doi.org/10.14814/phy2.13536 |
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2051-817X |
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WOS000425110700002.pdf |
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10.14814/phy2.13536 |
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Physiological Reports. Hoboken, v. 6, n. 3, p. -, 2018. 2051-817X WOS000425110700002.pdf 10.14814/phy2.13536 WOS:000425110700002 |
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https://repositorio.unifesp.br/handle/11600/54198 http://dx.doi.org/10.14814/phy2.13536 |
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