{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:38:43Z","timestamp":1785404323462,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,11]]},"group-title":"Physiology","reference-count":23,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01HL163159"],"award-info":[{"award-number":["R01HL163159"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R15EB035866"],"award-info":[{"award-number":["R15EB035866"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R15HL177713"],"award-info":[{"award-number":["R15HL177713"]}],"id":[{"id":"https:\/\/ror.org\/001d55x84","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Hyperactivity of the orexin system has been implicated in hypertension, yet the long-term impact of orexin 1 receptor (OX1R) overexpression in the paraventricular nucleus (PVN), a key brain region involved in arterial blood pressure (ABP) regulation, remains unclear. This study examined whether chronic OX1R overexpression in the PVN alters cardiovascular, neuroendocrine, and oxidative functions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Adult male Sprague\u2013Dawley rats received bilateral PVN injections of AAV2-OX1R or control virus AAV2-GFP. Their ABP and heart rate (HR) were monitored for eight weeks via radiotelemetry. Renal sympathetic nerve activity (RSNA) and ABP responses to PVN orexin A administration were assessed using in vivo recordings. Reactive oxygen species (ROS) were quantified using MitoProbe, and gene expression was analyzed by qPCR. Primary neuronal cultures were used to explore underlying mechanism involved in increased ROS production and neuronal activity.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>PVN OX1R overexpression increased mean ABP (\u223c10 mmHg), water intake, and ROS levels in both the PVN and peripheral organs. In addition, orexin A evoked exaggerated RSNA (155% vs. 73%) and pressor responses (27 vs. 16 mmHg) in PVN OX1R overexpression rats compared to control rats, these effects were attenuated by the OX1R antagonist SB408124. Plasma vasopressin levels were elevated, and brain sections confirmed increased ROS in OX1R-positive neurons. In vitro experiments further demonstrated that orexin A upregulated ROS-generating enzymes, suppressed antioxidant genes, and enhanced neuronal excitability.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Chronic PVN OX1R overexpression induces oxidative stress, sympathetic overactivity, and increased plasma vasopressin, contributing to hypertension development. Targeting PVN OX1R signaling may provide therapeutic benefit for hypertension.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.02.09.704927","type":"posted-content","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:15:25Z","timestamp":1770855325000},"source":"Crossref","is-referenced-by-count":0,"title":["Chronic Paraventricular OX1R Overexpression Induces Oxidative Stress and Hypertension in Rats"],"prefix":"10.64898","author":[{"given":"Peiying","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA"},{"name":"Guangdong Provincial Second Hospital of Traditional Chinese Medicine; Guangdong Provincial Engineering Technology Research Institute of Traditional Chinese Medicine; The Fifth Clinical College of Guangzhou University of Chinese Medicine; Guangdong Provincial Key Laboratory of Research and Development in Traditional Chinese Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasibeh","family":"Yousefzadehkharvanagh","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick","family":"Simet","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Michigan Technological University, Houghton, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingli","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA"},{"name":"School of Public Health,Chongqing Medical University, Chongqing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Michigan Technological University, Houghton, MI, USA"},{"name":"Department of Chemistry, Michigan Technological University, Houghton, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanrong","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Michigan Technological University, Houghton, MI, USA"},{"name":"Human Research Institute, Michigan Technological University, Houghton, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA"},{"name":"Human Research Institute, Michigan Technological University, Houghton, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Emergency, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiying","family":"Shan","sequence":"additional","affiliation":[{"name":"Department of Kinesiology and Integrative Physiology, Michigan Technological University, Houghton, MI, USA"},{"name":"Human Research Institute, Michigan Technological University, Houghton, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026021323250583000_2026.02.09.704927v1.1","doi-asserted-by":"publisher","DOI":"10.1159\/000123111"},{"key":"2026021323250583000_2026.02.09.704927v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-005-0290-7"},{"key":"2026021323250583000_2026.02.09.704927v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2015.08.012"},{"key":"2026021323250583000_2026.02.09.704927v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80892-2"},{"key":"2026021323250583000_2026.02.09.704927v1.5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00822.2016"},{"key":"2026021323250583000_2026.02.09.704927v1.6","doi-asserted-by":"crossref","first-page":"641331","DOI":"10.3389\/fphys.2021.641331","article-title":"Activation of Orexin 1 Receptors in the Paraventricular Nucleus Contributes to the Development of Deoxycorticosterone Acetate-Salt Hypertension Through Regulation of Vasopressin","volume":"12","year":"2021","journal-title":"Front Physiol"},{"key":"2026021323250583000_2026.02.09.704927v1.7","doi-asserted-by":"crossref","unstructured":"Y. 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