Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea

Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory...

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Autores: Olea, Elena, Valverde-Pérez, Esther, Docio, Inmaculada, Prieto-Lloret, Jesús, Aaronson, Philip I., Rocher, Asunción
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/380299
Acceso en línea:http://hdl.handle.net/10261/380299
Access Level:acceso abierto
Palabra clave:Systemic and pulmonary hypertension
Intermittent hypoxia
Hypoxic pulmonary vasoconstriction
Carotid body
Autonomic nervous system
Obstructive sleep apnea
Endothelial function
Vessel remodeling
Guinea pig
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spelling Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep ApneaOlea, ElenaValverde-Pérez, EstherDocio, InmaculadaPrieto-Lloret, JesúsAaronson, Philip I.Rocher, AsunciónSystemic and pulmonary hypertensionIntermittent hypoxiaHypoxic pulmonary vasoconstrictionCarotid bodyAutonomic nervous systemObstructive sleep apneaEndothelial functionVessel remodelingGuinea pigExperimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima–media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.This research was supported by grant reference BFU2015-70616-R from MINECOFEDER and by Programa Estrategico IBGM, Escalera de Excelencia, grant number CCVC8485, Consejeria de Educacion, Junta de Castilla y León (Spain).Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Economía y Competitividad (España)CSIC-UVA - Instituto de Biología y Genética Molecular (IBGM)Junta de Castilla y LeónConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/380299reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//BFU2015-70616-Rhttps://doi.org/10.3390/ijms25137484Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3802992026-05-22T06:33:51Z
dc.title.none.fl_str_mv Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea
title Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea
spellingShingle Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea
Olea, Elena
Systemic and pulmonary hypertension
Intermittent hypoxia
Hypoxic pulmonary vasoconstriction
Carotid body
Autonomic nervous system
Obstructive sleep apnea
Endothelial function
Vessel remodeling
Guinea pig
title_short Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea
title_full Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea
title_fullStr Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea
title_full_unstemmed Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea
title_sort Pulmonary Vascular Responses to Chronic Intermittent Hypoxia in a Guinea Pig Model of Obstructive Sleep Apnea
dc.creator.none.fl_str_mv Olea, Elena
Valverde-Pérez, Esther
Docio, Inmaculada
Prieto-Lloret, Jesús
Aaronson, Philip I.
Rocher, Asunción
author Olea, Elena
author_facet Olea, Elena
Valverde-Pérez, Esther
Docio, Inmaculada
Prieto-Lloret, Jesús
Aaronson, Philip I.
Rocher, Asunción
author_role author
author2 Valverde-Pérez, Esther
Docio, Inmaculada
Prieto-Lloret, Jesús
Aaronson, Philip I.
Rocher, Asunción
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
CSIC-UVA - Instituto de Biología y Genética Molecular (IBGM)
Junta de Castilla y León
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Systemic and pulmonary hypertension
Intermittent hypoxia
Hypoxic pulmonary vasoconstriction
Carotid body
Autonomic nervous system
Obstructive sleep apnea
Endothelial function
Vessel remodeling
Guinea pig
topic Systemic and pulmonary hypertension
Intermittent hypoxia
Hypoxic pulmonary vasoconstriction
Carotid body
Autonomic nervous system
Obstructive sleep apnea
Endothelial function
Vessel remodeling
Guinea pig
description Experimental evidence suggests that chronic intermittent hypoxia (CIH), a major hallmark of obstructive sleep apnea (OSA), boosts carotid body (CB) responsiveness, thereby causing increased sympathetic activity, arterial and pulmonary hypertension, and cardiovascular disease. An enhanced circulatory chemoreflex, oxidative stress, and NO signaling appear to play important roles in these responses to CIH in rodents. Since the guinea pig has a hypofunctional CB (i.e., it is a natural CB knockout), in this study we used it as a model to investigate the CB dependence of the effects of CIH on pulmonary vascular responses, including those mediated by NO, by comparing them with those previously described in the rat. We have analyzed pulmonary artery pressure (PAP), the hypoxic pulmonary vasoconstriction (HPV) response, endothelial function both in vivo and in vitro, and vascular remodeling (intima–media thickness, collagen fiber content, and vessel lumen area). We demonstrate that 30 days of the exposure of guinea pigs to CIH (FiO2, 5% for 40 s, 30 cycles/h) induces pulmonary artery remodeling but does not alter endothelial function or the contractile response to phenylephrine (PE) in these arteries. In contrast, CIH exposure increased the systemic arterial pressure and enhanced the contractile response to PE while decreasing endothelium-dependent vasorelaxation to carbachol in the aorta without causing its remodeling. We conclude that since all of these effects are independent of CB sensitization, there must be other oxygen sensors, beyond the CB, with the capacity to alter the autonomic control of the heart and vascular function and structure in CIH.
publishDate 2024
dc.date.none.fl_str_mv 2024
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/380299
url http://hdl.handle.net/10261/380299
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//BFU2015-70616-R
https://doi.org/10.3390/ijms25137484
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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