{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T05:46:12Z","timestamp":1780983972233,"version":"3.54.1"},"reference-count":64,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["32071106"],"award-info":[{"award-number":["32071106"]}]},{"name":"National Natural Science Foundation of China","award":["31871148"],"award-info":[{"award-number":["31871148"]}]},{"name":"National Natural Science Foundation of China","award":["81600958"],"award-info":[{"award-number":["81600958"]}]},{"name":"National Natural Science Foundation of China","award":["2022-LCYJ-PY-37"],"award-info":[{"award-number":["2022-LCYJ-PY-37"]}]},{"name":"Clinical Trials of the Affiliated Drum Tower Hospital, Medical School of Nanjing University","award":["32071106"],"award-info":[{"award-number":["32071106"]}]},{"name":"Clinical Trials of the Affiliated Drum Tower Hospital, Medical School of Nanjing University","award":["31871148"],"award-info":[{"award-number":["31871148"]}]},{"name":"Clinical Trials of the Affiliated Drum Tower Hospital, Medical School of Nanjing University","award":["81600958"],"award-info":[{"award-number":["81600958"]}]},{"name":"Clinical Trials of the Affiliated Drum Tower Hospital, Medical School of Nanjing University","award":["2022-LCYJ-PY-37"],"award-info":[{"award-number":["2022-LCYJ-PY-37"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Sympathetic overactivity contributes to the pathogenesis of sepsis. The selective \u03b12-adrenergic receptor agonist dexmedetomidine (DEX) is widely used for perioperative sedation and analgesia. We aimed to determine the central roles and mechanisms of DEX in attenuating sympathetic activity and inflammation in sepsis. Sepsis was induced by a single intraperitoneal injection of lipopolysaccharide (LPS) in rats. Effects of DEX were investigated 24 h after injection of LPS. Bilateral microinjection of DEX in the paraventricular nucleus (PVN) attenuated LPS-induced sympathetic overactivity, which was attenuated by the superoxide dismutase inhibitor DETC, cAMP analog db-cAMP or GABAA receptor antagonist gabazine. Superoxide scavenger tempol, NADPH oxidase inhibitor apocynin, adenylate cyclase inhibitor SQ22536 or PKA inhibitor Rp-cAMP caused similar effects to DEX in attenuating LPS-induced sympathetic activation. DEX inhibited LPS-induced superoxide and cAMP production, as well as NADPH oxidase, adenylate cyclase and PKA activation. The roles of DEX in reducing superoxide production and NADPH oxidase activation were attenuated by db-cAMP or gabazine. Intravenous infusion of DEX inhibited LPS-induced sympathetic overactivity, NOX activation, superoxide production, TNF-\u03b1 and IL-1\u03b2 upregulation in the PVN and plasma, as well as lung and renal injury, which were attenuated by the PVN microinjection of yohimbine and DETC. We conclude that activation of \u03b12-adrenergic receptors with DEX in the PVN attenuated LPS-induced sympathetic overactivity by reducing NADPH oxidase-dependent superoxide production via both inhibiting adenylate cyclase-cAMP-PKA signaling and activating GABAA receptors. The inhibition of NADPH oxidase-dependent superoxide production in the PVN partially contributes to the roles of intravenous infusion of DEX in attenuating LPS-induced sympathetic activation, oxidative stress and inflammation.<\/jats:p>","DOI":"10.3390\/antiox11122395","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T03:38:38Z","timestamp":1670211518000},"page":"2395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Dexmedetomidine Attenuates Lipopolysaccharide-Induced Sympathetic Activation and Sepsis via Suppressing Superoxide Signaling in Paraventricular Nucleus"],"prefix":"10.3390","volume":"11","author":[{"given":"Jin-Hua","family":"Bo","sequence":"first","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Anesthesiology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Xiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Liu","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yuan","family":"Hao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue-Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng-Liang","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3132-9592","authenticated-orcid":false,"given":"Guo-Qing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,2]]},"reference":[{"key":"ref_1","first-page":"e22112","article-title":"Sepsis Management, Controversies, and Advancement in Nanotechnology: A Systematic Review","volume":"14","author":"Choudhary","year":"2022","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4718","DOI":"10.7150\/thno.70974","article-title":"Norepinephrine acting on 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