{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T02:34:53Z","timestamp":1788489293811,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["Institutional Strategic Support Fund Award"],"award-info":[{"award-number":["Institutional Strategic Support Fund Award"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Umm Al-Qura University (Makkah, Saudi Arabia)","award":["PhD Scholarship"],"award-info":[{"award-number":["PhD Scholarship"]}]},{"name":"King Saud bin Abdulaziz University for Health Sciences (Riyadh, Saudi Arabia)","award":["PhD Scholarship"],"award-info":[{"award-number":["PhD Scholarship"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Reflex increases in breathing in response to acute hypoxia are dependent on activation of the carotid body (CB)\u2014A specialised peripheral chemoreceptor. Central to CB O2-sensing is their unique mitochondria but the link between mitochondrial inhibition and cellular stimulation is unresolved. The objective of this study was to evaluate if ex vivo intact CB nerve activity and in vivo whole body ventilatory responses to hypoxia were modified by alterations in succinate metabolism and mitochondrial ROS (mitoROS) generation in the rat. Application of diethyl succinate (DESucc) caused concentration-dependent increases in chemoafferent frequency measuring approximately 10\u201330% of that induced by severe hypoxia. Inhibition of mitochondrial succinate metabolism by dimethyl malonate (DMM) evoked basal excitation and attenuated the rise in chemoafferent activity in hypoxia. However, approximately 50% of the response to hypoxia was preserved. MitoTEMPO (MitoT) and 10-(6\u2032-plastoquinonyl) decyltriphenylphosphonium (SKQ1) (mitochondrial antioxidants) decreased chemoafferent activity in hypoxia by approximately 20\u201350%. In awake animals, MitoT and SKQ1 attenuated the rise in respiratory frequency during hypoxia, and SKQ1 also significantly blunted the overall hypoxic ventilatory response (HVR) by approximately 20%. Thus, whilst the data support a role for succinate and mitoROS in CB and whole body O2-sensing in the rat, they are not the sole mediators. Treatment of the CB with mitochondrial selective antioxidants may offer a new approach for treating CB-related cardiovascular\u2013respiratory disorders.<\/jats:p>","DOI":"10.3390\/antiox10060840","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T02:53:36Z","timestamp":1621911216000},"page":"840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Mitochondrial Succinate Metabolism and Reactive Oxygen Species Are Important but Not Essential for Eliciting Carotid Body and Ventilatory Responses to Hypoxia in the Rat"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6968-965X","authenticated-orcid":false,"given":"Agnieszka","family":"Swiderska","sequence":"first","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Manchester Academic Health Sciences Centre, Unit of Cardiac Physiology, 3.26 Core Technology Facility, Institute of Cardiovascular Sciences, The University of Manchester, 46 Grafton Street, Manchester M13 9NT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9451-4704","authenticated-orcid":false,"given":"Andrew M.","family":"Coney","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5973-2802","authenticated-orcid":false,"given":"Abdulaziz A.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Respiratory Care Department, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah 24381, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-8025","authenticated-orcid":false,"given":"Hayyaf S.","family":"Aldossary","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Basic Medical Sciences, College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh 11481, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2305-7427","authenticated-orcid":false,"given":"Nikolaos","family":"Batis","sequence":"additional","affiliation":[{"name":"Institute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare J.","family":"Ray","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prem","family":"Kumar","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9270-9401","authenticated-orcid":false,"given":"Andrew P.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Institute of Clinical Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"},{"name":"Institute of Cardiovascular Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1001\/jama.2020.12839","article-title":"Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19) A Review","volume":"324","author":"Wiersinga","year":"2020","journal-title":"JAMA J. 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