{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T20:29:53Z","timestamp":1793305793897,"version":"4.5.0"},"reference-count":37,"publisher":"American Society for Clinical Investigation","issue":"18","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81600557,81830020"],"award-info":[{"award-number":["81600557,81830020"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,22]]},"abstract":"<jats:p>The prevalence of hypertension is increasing globally, while strategies for prevention and treatment of hypertension remain limited. FG-4592 (Roxadustat) is a potentially novel, orally active small-molecule hypoxia-inducible factor (HIF) stabilizer and is being used clinically to treat chronic kidney disease (CKD) anemia. In the present study, we evaluate the effects of FG-4592 on hypertension. In an angiotensin II (Ang II) hypertension model, FG-4592 abolished hypertensive responses; prevented vascular thickening, cardiac hypertrophy, and kidney injury; downregulated AGTR1 expression; and enhanced AGTR2, endothelial NO synthase (eNOS), and HIF1\u03b1 protein levels in the aortas of mice. Additionally, the levels of thiobarbituric acid reactive substances (TBARs) in blood and urine were diminished by FG-4592 treatment. In vascular smooth muscle cells, FG-4592 treatment reduced angiotensin receptor type 1 (AGTR1) and increased AGTR2 levels, while preventing Ang II\u2013induced oxidative stress. In vascular endothelial cells, FG-4592 upregulated total and phosphorylated eNOS. Moreover, FG-4592 treatment was hypotensive in L-NAME\u2013induced hypertension. In summary, FG-4592 treatment remarkably ameliorated hypertension and organ injury, possibly through stabilizing HIF1\u03b1 and subsequently targeting eNOS, AGTR1, AGTR2, and oxidative stress. Therefore, in addition to its role in treating CKD anemia, FG-4592 could be explored as a treatment for hypertension associated with high renin angiotensin system (RAS) activity or eNOS defects.<\/jats:p>","DOI":"10.1172\/jci.insight.133690","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T12:00:41Z","timestamp":1629201641000},"source":"Crossref","is-referenced-by-count":51,"title":["Roxadustat prevents Ang II hypertension by targeting angiotensin receptors and eNOS"],"prefix":"10.1172","volume":"6","author":[{"given":"Jing","family":"Yu","sequence":"first","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics and"},{"name":"Department of Nephrology, Children\u2019s Hospital of Nanjing Medical University, Nanjing, China."},{"name":"Jiangsu Key Laboratory of Pediatrics, Nanjing Medical University, Nanjing, 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