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RT-PCR analysis indicated that the expression of CYP4A1, CYP4A2, CYP4A3, and CYP4A8 mRNA was increased two- to fourfold in cystic PCK compared with noncystic Sprague-Dawley rat kidneys. Daily administration of a 20-HETE synthesis inhibitor, HET-0016 (10 mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>ip) for 4\u20137 wk significantly reduced kidney size by 24% from 4.95 \u00b1 0.19 g in vehicle-treated PCK rats to 3.76 \u00b1 0.15 g ( n = 4). Collecting tubule morphometric cystic indices were reduced in HET-0016-treated PCK rats (2.1 \u00b1 0.2; n = 4) compared with vehicle-treated PCK rats (4.4 \u00b1 0.1; n = 4). The cellular mechanism by which 20-HETE may play a role in cyst formation has not been well characterized, but there was a significantly lower ( P &lt; 0.05) level of intracellular cAMP and decreased phosphorylation (activation) of ERK1\/2 protein in PCK rat kidneys ( n = 3) treated with HET-0016 . These studies indicate a potential role of 20-HETE in cyst formation in the orthologous rodent PCK model of ARPKD.<\/jats:p>","DOI":"10.1152\/ajprenal.90705.2008","type":"journal-article","created":{"date-parts":[[2009,1,8]],"date-time":"2009-01-08T01:34:25Z","timestamp":1231378465000},"page":"F575-F582","source":"Crossref","is-referenced-by-count":25,"title":["Chronic blockade of 20-HETE synthesis reduces polycystic kidney disease in an orthologous rat model of ARPKD"],"prefix":"10.1152","volume":"296","author":[{"given":"Frank","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"William E.","family":"Sweeney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangfu","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talha","family":"Akbulut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Mueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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