{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:09:01Z","timestamp":1780420141486,"version":"3.54.1"},"reference-count":48,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T00:00:00Z","timestamp":1643587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Background: Numerous studies have indicated that a high salt diet inhibits brain Na+\/K+-ATPase (NKA) activity, and affects oxidative stress and inflammation in the paraventricular nucleus (PVN). Furthermore, Na+\/K+-ATPase alpha 2-isoform (NKA \u03b12) may be a target in the brain, taking part in the development of salt-dependent hypertension. Therefore, we hypothesized that NKA \u03b12 regulates oxidative stress and inflammation in the PVN in the context of salt-induced hypertension. Methods: Part I: We assessed NKA subunits (NKA \u03b11, NKA \u03b12, and NKA \u03b13), Na+\/K+-ATPase activity, oxidative stress, and inflammation in a high salt group (8% NaCl) and normal salt group (0.3% NaCl). Part II: NKA \u03b12 short hairpin RNA (shRNA) was bilaterally microinjected into the PVN of salt-induced hypertensive rats to knockdown NKA \u03b12, and we explored whether NKA \u03b12 regulates downstream signaling pathways related to protein kinase C \u03b3 (PKC \u03b3)-dependent oxidative stress and toll-like receptor 4 (TLR4)-induced inflammation in the PVN to promote the development of hypertension. Results: High salt diet increased NKA \u03b11 and NKA \u03b12 protein expression in the PVN but had no effect on NKA \u03b13 compared to the normal salt diet. Na+\/K+-ATPase activity and ADP\/ATP ratio was lower, but NAD(P)H activity and NF-\u03baB activity in the PVN were higher after a high salt diet. Bilateral PVN microinjection of NKA \u03b12 shRNA not only improved Na+\/K+-ATPase activity and ADP\/ATP ratio but also suppressed PKC \u03b3-dependent oxidative stress and TLR4-dependent inflammation in the PVN, thus decreasing sympathetic activity in rats with salt-induced hypertension. Conclusions: NKA \u03b12 in the PVN elicits PKC \u03b3\/Rac1\/NAD (P)H-dependent oxidative stress and TLR4\/MyD88\/NF-\u03baB-induced inflammation in the PVN, thus increasing MAP and sympathetic activity during the development of salt-induced hypertension.<\/jats:p>","DOI":"10.3390\/antiox11020288","type":"journal-article","created":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T01:46:08Z","timestamp":1643593568000},"page":"288","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Na+\/K+-ATPase Alpha 2 Isoform Elicits Rac1-Dependent Oxidative Stress and TLR4-Induced Inflammation in the Hypothalamic Paraventricular Nucleus in High Salt-Induced Hypertension"],"prefix":"10.3390","volume":"11","author":[{"given":"Qing","family":"Su","sequence":"first","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology & Center for Brain Science, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Bao","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jie","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yan","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ming","family":"Kang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Shaanxi Engineering and Research Center of Vaccine, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"H1031","DOI":"10.1152\/ajpheart.00899.2011","article-title":"How NaCl raises blood pressure: A new paradigm for the pathogenesis of salt-dependent hypertension","volume":"302","author":"Blaustein","year":"2012","journal-title":"Am. 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