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β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia
Carotid body (CB) hyperactivity promotes hypertension in response to chronic intermittent hypoxia (CIH). The plasma concentration of adrenaline is reported to be elevated in CIH and our previous work suggests that adrenaline directly activates the CB. However, a role for chronic adrenergic stimulati...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782391/ https://www.ncbi.nlm.nih.gov/pubmed/33210151 http://dx.doi.org/10.1007/s00424-020-02492-0 |
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author | Alzahrani, Abdulaziz A. Cao, Lily L. Aldossary, Hayyaf S. Nathanael, Demitris Fu, Jiarong Ray, Clare J. Brain, Keith L. Kumar, Prem Coney, Andrew M. Holmes, Andrew P. |
author_facet | Alzahrani, Abdulaziz A. Cao, Lily L. Aldossary, Hayyaf S. Nathanael, Demitris Fu, Jiarong Ray, Clare J. Brain, Keith L. Kumar, Prem Coney, Andrew M. Holmes, Andrew P. |
author_sort | Alzahrani, Abdulaziz A. |
collection | PubMed |
description | Carotid body (CB) hyperactivity promotes hypertension in response to chronic intermittent hypoxia (CIH). The plasma concentration of adrenaline is reported to be elevated in CIH and our previous work suggests that adrenaline directly activates the CB. However, a role for chronic adrenergic stimulation in mediating CB hyperactivity is currently unknown. This study evaluated whether beta-blocker treatment with propranolol (Prop) prevented the development of CB hyperactivity, vascular sympathetic nerve growth and hypertension caused by CIH. Adult male Wistar rats were assigned into 1 of 4 groups: Control (N), N + Prop, CIH and CIH + Prop. The CIH paradigm consisted of 8 cycles h(−1), 8 h day(−1), for 3 weeks. Propranolol was administered via drinking water to achieve a dose of 40 mg kg(−1) day(−1). Immunohistochemistry revealed the presence of both β(1) and β(2)-adrenoceptor subtypes on the CB type I cell. CIH caused a 2–3-fold elevation in basal CB single-fibre chemoafferent activity and this was prevented by chronic propranolol treatment. Chemoafferent responses to hypoxia and mitochondrial inhibitors were attenuated by propranolol, an effect that was greater in CIH animals. Propranolol decreased respiratory frequency in normoxia and hypoxia in N and CIH. Propranolol also abolished the CIH mediated increase in vascular sympathetic nerve density. Arterial blood pressure was reduced in propranolol groups during hypoxia. Propranolol exaggerated the fall in blood pressure in most (6/7) CIH animals during hypoxia, suggestive of reduced sympathetic tone. These findings therefore identify new roles for β-adrenergic stimulation in evoking CB hyperactivity, sympathetic vascular hyperinnervation and altered blood pressure control in response to CIH. |
format | Online Article Text |
id | pubmed-7782391 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-77823912021-01-11 β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia Alzahrani, Abdulaziz A. Cao, Lily L. Aldossary, Hayyaf S. Nathanael, Demitris Fu, Jiarong Ray, Clare J. Brain, Keith L. Kumar, Prem Coney, Andrew M. Holmes, Andrew P. Pflugers Arch Integrative Physiology Carotid body (CB) hyperactivity promotes hypertension in response to chronic intermittent hypoxia (CIH). The plasma concentration of adrenaline is reported to be elevated in CIH and our previous work suggests that adrenaline directly activates the CB. However, a role for chronic adrenergic stimulation in mediating CB hyperactivity is currently unknown. This study evaluated whether beta-blocker treatment with propranolol (Prop) prevented the development of CB hyperactivity, vascular sympathetic nerve growth and hypertension caused by CIH. Adult male Wistar rats were assigned into 1 of 4 groups: Control (N), N + Prop, CIH and CIH + Prop. The CIH paradigm consisted of 8 cycles h(−1), 8 h day(−1), for 3 weeks. Propranolol was administered via drinking water to achieve a dose of 40 mg kg(−1) day(−1). Immunohistochemistry revealed the presence of both β(1) and β(2)-adrenoceptor subtypes on the CB type I cell. CIH caused a 2–3-fold elevation in basal CB single-fibre chemoafferent activity and this was prevented by chronic propranolol treatment. Chemoafferent responses to hypoxia and mitochondrial inhibitors were attenuated by propranolol, an effect that was greater in CIH animals. Propranolol decreased respiratory frequency in normoxia and hypoxia in N and CIH. Propranolol also abolished the CIH mediated increase in vascular sympathetic nerve density. Arterial blood pressure was reduced in propranolol groups during hypoxia. Propranolol exaggerated the fall in blood pressure in most (6/7) CIH animals during hypoxia, suggestive of reduced sympathetic tone. These findings therefore identify new roles for β-adrenergic stimulation in evoking CB hyperactivity, sympathetic vascular hyperinnervation and altered blood pressure control in response to CIH. Springer Berlin Heidelberg 2020-11-19 2021 /pmc/articles/PMC7782391/ /pubmed/33210151 http://dx.doi.org/10.1007/s00424-020-02492-0 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Integrative Physiology Alzahrani, Abdulaziz A. Cao, Lily L. Aldossary, Hayyaf S. Nathanael, Demitris Fu, Jiarong Ray, Clare J. Brain, Keith L. Kumar, Prem Coney, Andrew M. Holmes, Andrew P. β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia |
title | β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia |
title_full | β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia |
title_fullStr | β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia |
title_full_unstemmed | β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia |
title_short | β-Adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia |
title_sort | β-adrenoceptor blockade prevents carotid body hyperactivity and elevated vascular sympathetic nerve density induced by chronic intermittent hypoxia |
topic | Integrative Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782391/ https://www.ncbi.nlm.nih.gov/pubmed/33210151 http://dx.doi.org/10.1007/s00424-020-02492-0 |
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