{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:55:04Z","timestamp":1777485304839,"version":"3.51.4"},"reference-count":50,"publisher":"S. Karger AG","issue":"3-4","license":[{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2016,1,1]],"date-time":"2016-01-01T00:00:00Z","timestamp":1451606400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Vasc Res"],"published-print":{"date-parts":[[2016]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Background\/Aims:&lt;\/i&gt;&lt;\/b&gt; Chronic kidney disease (CKD) is associated with large artery remodeling, endothelial dysfunction and calcification, with angiotensin II (Ang II) a known driver of these pathologies. We investigated long-term Ang II type 1 receptor inhibition with valsartan on aortic function and structure in the Lewis polycystic kidney (LPK) rat model of CKD. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; Mixed sex LPK and Lewis control (total &lt;i&gt;n&lt;\/i&gt; = 28) treated (valsartan 60 mg\/kg\/day p.o. from 4 to 18 weeks) and vehicle groups were studied. Functional responses to noradrenaline (NA), potassium chloride and endothelium-dependent and independent relaxations were investigated in vitro using acetylcholine hydrochloride (ACh) and sodium nitroprusside (SNP), respectively. Effects of the nitric oxide synthase (NOS) substrate &lt;smlcap&gt;L&lt;\/smlcap&gt;-arginine, NOS inhibitor &lt;smlcap&gt;L&lt;\/smlcap&gt;-NAME and cyclooxygenase inhibitor indomethacin on ACh responses were examined. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; In the LPK, valsartan reduced systolic blood pressure and urinary protein, ameliorated exaggerated sensitivity to NA, and normalized endothelium-dependent (ACh-R&lt;sub&gt;max&lt;\/sub&gt;; 91 \u00b1 7 vs. 59 \u00b1 6%, &lt;i&gt;p&lt;\/i&gt; = 0.0001) and independent dysfunction (SNP-R&lt;sub&gt;max&lt;\/sub&gt;; 99 \u00b1 1 vs. 82 \u00b1 7%, &lt;i&gt;p&lt;\/i&gt; = 0.040), as well as improving NO-dependent relaxation (R&lt;sub&gt;max&lt;\/sub&gt;; -51 \u00b1 6 vs. -26 \u00b1 9%, &lt;i&gt;p&lt;\/i&gt; = 0.008). Valsartan also reduced aortic wall hypertrophy, elastin disruption\/fragmentation, calcification, media cystic degeneration, and levels of matrix metalloproteinase 9. &lt;b&gt;&lt;i&gt;Conclusions:&lt;\/i&gt;&lt;\/b&gt; This study highlights the role of Ang II in driving vascular manifestations of CKD and indicates that early treatment can significantly limit pathological changes.<\/jats:p>","DOI":"10.1159\/000452411","type":"journal-article","created":{"date-parts":[[2016,11,23]],"date-time":"2016-11-23T22:01:46Z","timestamp":1479938506000},"page":"216-229","source":"Crossref","is-referenced-by-count":16,"title":["Long-Term Angiotensin II Receptor Blockade Limits Hypertension, Aortic Dysfunction, and Structural Remodeling in a Rat Model of Chronic Kidney Disease"],"prefix":"10.1159","volume":"53","author":[{"given":"Omar Z.","family":"Ameer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2746-4222","authenticated-orcid":false,"given":"Mark","family":"Butlin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Kaschina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela","family":"Sommerfeld","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8311-2010","authenticated-orcid":false,"given":"Alberto P.","family":"Avolio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4917-7734","authenticated-orcid":false,"given":"Jacqueline 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