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Renal blood flow (RBF), mean arterial pressure (MAP), and heart rate (HR) were continuously measured and urine was collected directly from the left ureter. Intraperitoneal injection of luseogliflozin (0.9\u2009mg\u2009kg<jats:sup>\u22121<\/jats:sup>) did not change MAP, HR, RBF, or creatinine clearance (CrCl) in SD rats (<jats:italic>n<\/jats:italic>\u2009=\u20097). Luseogliflozin significantly increased urine volume, which was associated with significantly increased urinary glucose excretion rates (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Similarly, luseogliflozin significantly increased urinary sodium excretion (from 0.07\u2009\u00b1\u20090.01\u2009\u00b5mol min<jats:sup>\u22121<\/jats:sup>at baseline to 0.76\u2009\u00b1\u20090.08\u2009\u00b5mol min<jats:sup>\u22121<\/jats:sup>at 120\u2009min;<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001). Furthermore, luseogliflozin resulted in significantly increased urinary pH (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and decreased urinary osmolality and urea concentration (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) in SD rats. Similarly, in Nx SD rats (<jats:italic>n<\/jats:italic>\u2009=\u20095\u20136), luseogliflozin significantly increased urine volume and urinary glucose excretion (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) without altering MAP, HR, RBF, or CrCl. Luseogliflozin did not elicit any significant effects on the other urinary parameters in Nx SD rats. These data indicate that SGLT2 inhibitor elicits direct tubular effects in non-diabetic rats with normal renal functions.<\/jats:p>","DOI":"10.1038\/s41598-017-09352-5","type":"journal-article","created":{"date-parts":[[2017,8,21]],"date-time":"2017-08-21T15:44:45Z","timestamp":1503330285000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Responses of renal hemodynamics and tubular functions to acute sodium\u2013glucose cotransporter 2 inhibitor administration in non-diabetic anesthetized rats"],"prefix":"10.1038","volume":"7","author":[{"given":"Tuba M.","family":"Ansary","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihide","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9172-5343","authenticated-orcid":false,"given":"Asadur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daisuke","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirofumi","family":"Hitomi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Kobara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsutomu","family":"Masaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens M.","family":"Titze","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kento","family":"Kitada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akira","family":"Nishiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,25]]},"reference":[{"key":"9352_CR1","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1124\/jpet.113.203869","volume":"345","author":"N Kojima","year":"2013","unstructured":"Kojima, N., Williams, J. 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