{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T06:26:55Z","timestamp":1740119215233,"version":"3.37.3"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2018,2,7]],"date-time":"2018-02-07T00:00:00Z","timestamp":1517961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1030297"],"award-info":[{"award-number":["GNT1030297"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>The renin\u2013angiotensin system, in particular Angiotensin II (AngII), plays a significant role in the pathogenesis of hypertension in chronic kidney disease (CKD). Effects of chronic AT1 receptor antagonism were investigated in a genetic hypertensive rat model of CKD, the Lewis polycystic kidney (LPK) rat.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>Mixed-sex LPK and Lewis control rats (total n = 31) were split between treated (valsartan 60 mg\/kg\/day p.o. from 4 to 18 weeks) and vehicle groups. Animals were assessed for systolic blood pressure and urine biochemistry, and after euthanasia, blood collected for urea and creatinine analysis, confirming the hypertensive and renal phenotype. Mesenteric resistance vasculature was assessed using pressure myography and histology.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Valsartan treatment improved vascular structure in LPK rats, increasing internal and external diameter values and reducing wall thickness (untreated vs. treated LPK: 53.19 \u00b1 3.29 vs. 33.93 \u00b1 2.17 \u03bcm) and wall\u2013lumen ratios (untreated vs. treated LPK: 0.52 \u00b1 0.09 vs. 0.16 \u00b1 0.01, all P &amp;lt; 0.0001). Endothelium dysfunction, as measured by maximal response to acetylcholine (Rmax), was normalized with treatment (untreated vs. treated LPK: 69.56 \u00b1 4.34 vs. 103.05 \u00b1 4.13, P &amp;lt; 0.05), increasing the relative contributions of nitric oxide and endothelium-derived hyperpolarization to vasorelaxation while downregulating the prostanoid contribution. Biomechanical properties also improved with treatment, as indicated by an increase in compliance, decrease in intrinsic stiffness and alterations in the artery wall composition, which included decreases in collagen density and collagen\/elastin ratio.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>Our results highlight the importance of AngII as a driver of resistance vessel structural, functional, and biomechanical dysfunction and provide insight as to how AT1 receptor blockade exerts therapeutic efficacy in CKD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajh\/hpy021","type":"journal-article","created":{"date-parts":[[2018,2,6]],"date-time":"2018-02-06T12:08:08Z","timestamp":1517918888000},"page":"696-705","source":"Crossref","is-referenced-by-count":7,"title":["AT1 Receptor Antagonism Improves Structural, Functional, and Biomechanical Properties in Resistance Arteries in a Rodent Chronic Kidney Disease Model"],"prefix":"10.1093","volume":"31","author":[{"given":"Ko Jin","family":"Quek","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar Z","family":"Ameer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia"},{"name":"Colleges of Medicine and Pharmacy, Alfaisal University, Riyadh, Kingdom of Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline K","family":"Phillips","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,2,7]]},"reference":[{"key":"2024012317004888800_CIT0001","doi-asserted-by":"crossref","first-page":"54","DOI":"10.15420\/usc.2009.6.2.54","article-title":"Treatment of hypertension in patients with chronic kidney disease","volume":"6","author":"Cohen","year":"2009","journal-title":"US Cardiol"},{"key":"2024012317004888800_CIT0002","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1523-1755.2005.09911.x","article-title":"The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease","volume":"68","author":"Remuzzi","year":"2005","journal-title":"Kidney Int"},{"key":"2024012317004888800_CIT0003","doi-asserted-by":"crossref","first-page":"28668","DOI":"10.1074\/jbc.M113.470971","article-title":"Nox4 NADPH oxidase mediates peroxynitrite-dependent uncoupling of endothelial nitric-oxide synthase and fibronectin expression in response to angiotensin II: role of mitochondrial reactive oxygen species","volume":"288","author":"Lee","year":"2013","journal-title":"J Biol Chem"},{"key":"2024012317004888800_CIT0004","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.yjmcc.2013.10.013","article-title":"Angiotensin II induces Fat1 expression\/activation and vascular smooth muscle cell migration via Nox1-dependent reactive oxygen species generation","volume":"66","author":"Bruder-Nascimento","year":"2014","journal-title":"J Mol Cell Cardiol"},{"key":"2024012317004888800_CIT0005","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1161\/01.CIR.99.3.392","article-title":"Role of extracellular signal-regulated kinases in angiotensin II-stimulated contraction of smooth muscle cells from human resistance arteries","volume":"99","author":"Touyz","year":"1999","journal-title":"Circulation"},{"key":"2024012317004888800_CIT0006","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1172\/JCI115881","article-title":"Vascular smooth muscle cell hypertrophy vs. hyperplasia. 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