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Urea transporter (UT) inhibition increases the excretion of water and urea, but the effect on uremic cardiomyopathy has not been studied. We tested UT inhibition by dimethylthiourea (DMTU) in 5\/6 nephrectomy mice. This treatment suppressed CKD\u2010induced hypertension and cardiac hypertrophy. In CKD mice, cardiac fibrosis was associated with upregulation of UT and vimentin abundance. Inhibition of UT suppressed vimentin amount. Left ventricular mass index in DMTU\u2010treated CKD was less compared with non\u2010treated CKD mice as measured by echocardiography. Nephrectomy was performed in UT\u2010A1\/A3 knockout (UT\u2010KO) to further confirm our finding. UT\u2010A1\/A3 deletion attenuates the CKD\u2010induced increase in cardiac fibrosis and hypertension. The amount of \u03b1\u2010smooth muscle actin and tgf\u2010\u03b2 were significantly less in UT\u2010KO with CKD than WT\/CKD mice. To study the possibility that UT inhibition could benefit heart, we measured the mRNA of renin and angiotensin\u2010converting enzyme (ACE), and found both were sharply increased in CKD heart; DMTU treatment and UT\u2010KO significantly abolished these increases. Conclusion: Inhibition of UT reduced hypertension, cardiac fibrosis, and improved heart function. These changes are accompanied by inhibition of renin and ACE.<\/jats:p>","DOI":"10.1096\/fj.202000214rr","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T01:19:30Z","timestamp":1588641570000},"page":"8296-8309","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Inhibition of urea transporter ameliorates uremic cardiomyopathy in chronic kidney disease"],"prefix":"10.1096","volume":"34","author":[{"given":"Akihiro","family":"Kuma","sequence":"first","affiliation":[{"name":"Renal Division Department of Medicine Emory University School of Medicine Atlanta GA USA"},{"name":"Second Department of Internal Medicine School of Medicine University of Occupational and Environmental Health Kitakyushu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division Department of Medicine Emory 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