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The median survival time for affected patients is only 2\u20134\u00a0weeks. Treatment options for HRS are very limited. The absence of an established animal model that accurately reflects human disease has hindered efforts to find treatment targets. We aimed to describe the renal hemodynamic changes that occur over time in the rat common bile duct ligation (BDL) model of cirrhosis. Male Sprague-Dawley rats underwent BDL or sham surgery and were studied at 2\u20135\u00a0weeks post-surgery. BDL caused persistent liver failure, which was linked to the development of liver fibrosis as early as 2\u00a0weeks. Renal function declined over time. Arterial blood pressure was significantly lower at 3\u00a0weeks after BDL and worsened further by 5\u00a0weeks. Additionally, renal blood flow, essential for kidney function, was dramatically reduced in BDL rats by 3\u00a0weeks. Decreased renal blood flow correlated with increased thromboxane synthase mRNA expression and higher thromboxane levels from 2 to 5\u00a0weeks in BDL rats. Similarly, enhanced constriction of the afferent arteriole in response to the thromboxane mimic, U46619, was seen at 2\u00a0weeks but not at 4\u00a0weeks in BDL rats. Levels of endothelin-1 increased between 2 and 5\u00a0weeks and were associated with heightened afferent arteriolar constriction in BDL rats. The rat BDL model replicates key systemic and renal hemodynamic features of decompensated cirrhosis in humans and provides a practical animal model for studying and developing therapies for HRS-AKI.<\/jats:p>","DOI":"10.1042\/cs20257052","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:57:14Z","timestamp":1773665834000},"page":"571-587","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Renal hemodynamics underlie hepatorenal physiology in bile duct-ligated rats"],"prefix":"10.1042","volume":"140","author":[{"given":"Michael\u00a0M.","family":"Yeboah","sequence":"first","affiliation":[{"name":"1Department of Medicine, Medical College of Wisconsin, Mil\u00adwaukee, WI, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md.\u00a0Abdul","family":"Hye Khan","sequence":"additional","affiliation":[{"name":"2Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marla\u00a0A.","family":"Chesnik","sequence":"additional","affiliation":[{"name":"3Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, WI, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Atamanchuk","sequence":"additional","affiliation":[{"name":"4Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsigereda\u00a0G.","family":"Weldemichael","sequence":"additional","affiliation":[{"name":"2Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samaneh","family":"Goorani","sequence":"additional","affiliation":[{"name":"2Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilham","family":"Kadhim","sequence":"additional","affiliation":[{"name":"2Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin\u00a0R.","family":"Regner","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Medical College of Wisconsin, Mil\u00adwaukee, WI, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9668-2899","authenticated-orcid":false,"given":"John\u00a0D.","family":"Imig","sequence":"additional","affiliation":[{"name":"1Department of Medicine, Medical College of Wisconsin, Mil\u00adwaukee, WI, U.S.A."},{"name":"2Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"2026033004563241000_B1","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41581-019-0218-4","article-title":"Reappraising the spectrum of AKI and hepatorenal syndrome in patients with cirrhosis","volume":"16","author":"Velez","year":"2020","journal-title":"Nat. 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