{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T22:10:54Z","timestamp":1759961454974},"reference-count":65,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,10,29]],"date-time":"2012-10-29T00:00:00Z","timestamp":1351468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Exp Pharma Physio"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>\n<jats:list>\n\n<jats:list-item><jats:p>In the present study, we tested whether polycystic kidney disease (<jats:styled-content style=\"fixed-case\">PKD<\/jats:styled-content>) is associated with renal tissue hypoxia and oxidative stress, which, in turn, contribute to the progression of cystic disease and hypertension.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Lewis polycystic kidney (<jats:styled-content style=\"fixed-case\">LPK<\/jats:styled-content>) rats and Lewis control (Lewis) rats were treated with tempol (1\u00a0mmol\/L in drinking water) from 3 to 13\u00a0weeks of age or remained untreated.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>The <jats:styled-content style=\"fixed-case\">LPK<\/jats:styled-content> rats developed polyuria, uraemia and proteinuria. At 13\u00a0weeks of age, <jats:styled-content style=\"fixed-case\">LPK<\/jats:styled-content> rats had greater mean arterial pressure (1.5\u2010fold), kidney weight (sixfold) and plasma creatinine (3.5\u2010fold) than Lewis rats. Kidneys from <jats:styled-content style=\"fixed-case\">LPK<\/jats:styled-content> rats were cystic and fibrotic.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Renal hypoxia was evidenced by staining for pimonidazole adducts and hypoxia\u2010inducible factor (<jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>)\u20101\u03b1 in cells lining renal cysts and upregulation of <jats:styled-content style=\"fixed-case\">HIF<\/jats:styled-content>\u20101\u03b1 and its downstream targets vascular endothelial growth factor (<jats:styled-content style=\"fixed-case\">VEGF<\/jats:styled-content>), glucose transporter\u20101 (Glut\u20101) and heme oxygenase 1 (<jats:styled-content style=\"fixed-case\">HO<\/jats:styled-content>\u20101). However, total <jats:styled-content style=\"fixed-case\">HO<\/jats:styled-content> activity did not differ greatly between kidney tissue from <jats:styled-content style=\"fixed-case\">LPK<\/jats:styled-content> compared with Lewis rats.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Renal oxidative and\/or nitrosative stress was evidenced by ninefold greater immunofluorescence for 3\u2010nitrotyrosine in kidney tissue from LPK compared with Lewis rats and a\u00a0&gt;\u00a010\u2010fold upregulation of <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> for <jats:italic>p47phox<\/jats:italic> and <jats:italic>gp91phox<\/jats:italic>. Total renal superoxide dismutase (SOD) activity was sevenfold less and expression of <jats:italic>SOD1 <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> was 70% less in kidney tissue from LPK compared with Lewis rats. In LPK rats, tempol treatment reduced immunofluorescence for 3\u2010nitrotyrosine and <jats:italic>HIF1A <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> while upregulating <jats:italic>VEGF<\/jats:italic> and <jats:italic>p47phox <\/jats:italic><jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> expression, but otherwise had little impact on disease progression, renal tissue hypoxia or hypertension.<\/jats:p><\/jats:list-item>\n\n<jats:list-item><jats:p>Our findings do not support the hypothesis that oxidative stress drives hypoxia and disease progression in <jats:styled-content style=\"fixed-case\">PKD<\/jats:styled-content>.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1111\/1440-1681.12013","type":"journal-article","created":{"date-parts":[[2012,9,25]],"date-time":"2012-09-25T19:09:07Z","timestamp":1348600147000},"page":"917-929","source":"Crossref","is-referenced-by-count":17,"title":["Chronic treatment with tempol does not significantly ameliorate renal tissue hypoxia or disease progression in a rodent model of polycystic kidney disease"],"prefix":"10.1111","volume":"39","author":[{"given":"Alice","family":"Ding","sequence":"first","affiliation":[{"name":"The Australian School of Advanced Medicine Macquarie University Sydney NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priyadharshani","family":"Kalaignanasundaram","sequence":"additional","affiliation":[{"name":"Department of Physiology Monash University Melbourne Vic. 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