You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I1 Apr 2018MP10-01 NICORANDIL INCREASES RENAL NITRIC OXIDE (NO), DECREASES TRASFORMING GROWTH FACTOR (TGF)-β, AND AMELIORATES RENAL INJURY IN UNILATERAL URETERAL OBSTRUCTION (UUO) IN RATS Ayako Masunaga, Keiichi Ito, Takako Asano, Hitoshi Tsuda, and Tomohiko Asano Ayako MasunagaAyako Masunaga More articles by this author , Keiichi ItoKeiichi Ito More articles by this author , Takako AsanoTakako Asano More articles by this author , Hitoshi TsudaHitoshi Tsuda More articles by this author , and Tomohiko AsanoTomohiko Asano More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.347AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Nicorandil (NICO) is a vasodilatory agent which can augment NO production, and is broadly used in clinical for angina treatment. Renoprotective effects of NICO have also been shown in several renal disease models such as hypertensive renal injury and diabetic nephropathy models. The present study was undertaken to evaluate the effects of NICO on mediators including NO and TGF-β, and parameters of renal injury in a rat UUO model. METHODS Experiment 1; 24 hr urine samples from SD/SPF rats were collected after 2 days injection of DMSO, NICO, and NICO+L-NAME (NOS inhibitor), for measurement of urinary NO2 /NO3 (UNO). Experiment 2; Three groups were subject to left UUO. Group 1: control (intraperitoneal injection of DMSO beginning 2 days prior to UUO and continuing throughout study, n=10). Group 2: NICO treatment (same protocol as group 1, n=10). Group 3: NICO+L-NAME (NOS inhibitor) treatment (same protocol as group 1, n=10). Kidneys were harvested at day 14 after UUO. The following was examined: interstitial fibrosis, point counting of Masson's trichrome-stained slides and fibroblast specific protein (FSP) immunostaining; machrophage and eNOS, immunohistochemistry; apoptosis, ssDNA immunostaining; TGF-β, ELISA. RESULTS Experiment 1; UNO was significantly higher after NICO treatment than after DMSO (514.1±47.0 vs. 262.9±26.5 µmol/24hr/100g, p=0.0004), confirming increased NO production in the kidney. Experiment 2; Tissue TGF-β levels were lower in NICO group than in control (6.3±1.8 vs. 11.3±1.6 pg/mg tissue). Increased eNOS expression in NICO group was demonstrated in vascular endothelial cells by immunohistochemistry. Interstitial fibrosis in obstructed kidney was significantly decreased in NICO group compared to control (See table). Machrophages and apoptotic cells in obstructed kidney were significantly decreased by NICO treatment (See table). These renoprotective effects were blunted by L-NAME. CONCLUSIONS NICO increased renal NO, decreased renal TGF-β, and improved tubular apoptosis, renal fibrosis and macrophage infiltration in UUO. It may represent a useful new tool for UUO treatment. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e115 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ayako Masunaga More articles by this author Keiichi Ito More articles by this author Takako Asano More articles by this author Hitoshi Tsuda More articles by this author Tomohiko Asano More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
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