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High-output heart failure was induced by creating an aorto-caval fistula (ACF). After five weeks, rats were either left untreated or treatment with ACEi or ARB was started for 15\u00a0weeks. Subsequently, echocardiographic, renal hemodynamic and biochemical measurements were assessed. Untreated ACF rats with ACF displayed significantly reduced renal blood flow (RBF) (HanSD: 8.9\u2009\u00b1\u20091.0 vs. 4.7\u2009\u00b1\u20091.6; TGR: 10.2\u2009\u00b1\u20091.9 vs. 5.9\u2009\u00b1\u20091.2\u00a0ml\/min, both <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001), ACEi had no major RBF effect, whereas ARB completely restored RBF (HanSD: 5.6\u2009\u00b1\u20091.1 vs. 9.0\u2009\u00b1\u20091.5; TGR: 7.0\u2009\u00b1\u20091.2 vs. 10.9\u2009\u00b1\u20091.9\u00a0ml\/min, both <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001). RBF reduction in untreated and ACEi-treated rats was accompanied by renal hypoxia as measured by renal lactate dehydrogenase activity, which was ameliorated with ARB treatment (HanSD: 40\u2009\u00b1\u20094 vs. 42\u2009\u00b1\u20093 vs. 29\u2009\u00b1\u20095; TGR: 88\u2009\u00b1\u20094 vs. 76\u2009\u00b1\u20094 vs. 58\u2009\u00b1\u20094 milliunits\/mL, all <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.01). Unlike improvement seen in ARB-treated rats, ACE inhibition didn\u2019t affect urinary nitrates compared to untreated ACF TGR rats (50\u2009\u00b1\u200914 vs. 22\u2009\u00b1\u200913 vs. 30\u2009\u00b1\u200913\u00a0\u03bcmol\/mmol Cr, both <jats:italic>P<\/jats:italic>\u2009&lt;\u2009.05). ARB was more effective than ACEi in reducing elevated renal oxidative stress following ACF placement. A marker of ACEi efficacy, the angiotensin I\/angiotensin II ratio, was more than ten times lower in renal tissue than in plasma. Our study shows that ARB treatment, in contrast to ACEi administration, prevents renal hypoperfusion and hypoxia in ACF rats with concomitant improvement in NO bioavailability and oxidative stress reduction. The inability of ACE inhibition to improve renal hypoperfusion in ACF rats may result from incomplete intrarenal RAS suppression in the face of depleted compensatory mechanisms.<\/jats:p>","DOI":"10.1038\/s41598-021-83906-6","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T16:02:53Z","timestamp":1613836973000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["AT1 receptor blocker, but not an ACE inhibitor, prevents kidneys from hypoperfusion during congestive heart failure in normotensive and hypertensive rats"],"prefix":"10.1038","volume":"11","author":[{"given":"Vojtech","family":"Kratky","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenka","family":"Vanourkova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matus","family":"Sykora","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Szeiffova","family":"Bacova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenka","family":"Hruskova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sona","family":"Kikerlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Huskova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Libor","family":"Kopkan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,19]]},"reference":[{"key":"83906_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.15420\/cfr.2016:25:2","volume":"3","author":"G Savarese","year":"2017","unstructured":"Savarese, G. & Lund, L. 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