{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T11:08:31Z","timestamp":1791889711181,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Natural Science Foundation of China","award":["31871148"],"award-info":[{"award-number":["31871148"]}]},{"name":"the National Natural Science Foundation of China","award":["32071106"],"award-info":[{"award-number":["32071106"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Asprosin is a newly discovered adipokine that is involved in regulating metabolism. Sympathetic overactivity contributes to the pathogenesis of several cardiovascular diseases. The paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the regulation of sympathetic outflow and blood pressure. This study was designed to determine the roles and underlying mechanisms of asprosin in the PVN in regulating sympathetic outflow and blood pressure. Experiments were carried out in male adult SD rats under anesthesia. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were recorded, and PVN microinjections were performed bilaterally. Asprosin mRNA and protein expressions were high in the PVN. The high asprosin expression in the PVN was involved in both the parvocellular and magnocellular regions according to immunohistochemical analysis. Microinjection of asprosin into the PVN produced dose-related increases in RSNA, MAP, and HR, which were abolished by superoxide scavenger tempol, antioxidant N-acetylcysteine (NAC), and NADPH oxidase inhibitor apocynin. The asprosin promoted superoxide production and increased NADPH oxidase activity in the PVN. Furthermore, it increased the cAMP level, adenylyl cyclase (AC) activity, and protein kinase A (PKA) activity in the PVN. The roles of asprosin in increasing RSNA, MAP, and HR were prevented by pretreatment with AC inhibitor SQ22536 or PKA inhibitor H89 in the PVN. Microinjection of cAMP analog db-cAMP into the PVN played similar roles with asprosin in increasing the RSNA, MAP, and HR, but failed to further augment the effects of asprosin. Pretreatment with PVN microinjection of SQ22536 or H89 abolished the roles of asprosin in increasing superoxide production and NADPH oxidase activity in the PVN. These results indicated that asprosin in the PVN increased the sympathetic outflow, blood pressure, and heart rate via cAMP\u2013PKA signaling-mediated NADPH oxidase activation and the subsequent superoxide production.<\/jats:p>","DOI":"10.3390\/ijms232012595","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T22:49:46Z","timestamp":1666306186000},"page":"12595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Asprosin in the Paraventricular Nucleus Induces Sympathetic Activation and Pressor Responses via cAMP-Dependent ROS Production"],"prefix":"10.3390","volume":"23","author":[{"given":"Xiao-Li","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing 211166, 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 of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing 211166, 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 of Translational Medicine for Cardiovascular Disease, 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 of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Zhou","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Emergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Qin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Emergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Tong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Emergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Qi","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Emergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, 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"}]},{"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 of Translational Medicine for Cardiovascular Disease, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiu-Zhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Emergency Department, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jash.2016.02.015","article-title":"Evidence for a critical role of the sympathetic nervous system in hypertension","volume":"10","author":"Grassi","year":"2016","journal-title":"J. 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