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Inducible Nitric Oxide Synthase Promotes Pathophysiological Consequences of Experimental Bladder Outlet Obstruction

2003; Lippincott Williams & Wilkins; Volume: 169; Issue: 4 Linguagem: Inglês

10.1097/01.ju.0000054885.51858.99

1527-3792

Diane Felsen, Kambiz Dardashti, Michael Ostad, Matthew L. Lemer, Steven S. Gross, Jie Chen, E D Vaughan, Dix P. Poppas,

Aldose Reductase and Taurine

No AccessJournal of UrologyINVESTIGATIVE UROLOGY1 Apr 2003Inducible Nitric Oxide Synthase Promotes Pathophysiological Consequences of Experimental Bladder Outlet Obstruction DIANE FELSEN, KAMBIZ DARDASHTI, MICHAEL OSTAD, MATTHEW L. LEMER, STEVEN S. GROSS, JIE CHEN, E.D. VAUGHAN, and DIX P. POPPAS DIANE FELSENDIANE FELSEN , KAMBIZ DARDASHTIKAMBIZ DARDASHTI , MICHAEL OSTADMICHAEL OSTAD , MATTHEW L. LEMERMATTHEW L. LEMER , STEVEN S. GROSSSTEVEN S. GROSS , JIE CHENJIE CHEN , E.D. VAUGHANE.D. VAUGHAN , and DIX P. POPPASDIX P. POPPAS View All Author Informationhttps://doi.org/10.1097/01.ju.0000054885.51858.99AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Bladder outlet obstruction leads to histological and functional changes in the bladder over time. We investigated the role of inducible nitric oxide synthase (iNOS) in the progression of pathological changes of the bladder secondary to outlet obstruction in a rat and a mouse model. Materials and Methods: To assess expression of iNOS in the bladder, polymerase chain reaction amplification of mRNA was done. Rats were subjected to sham operation or partial bladder outlet obstruction. They were given the iNOS inhibitor aminoguanidine in drinking water or unmodified water. After 2 weeks, awake cystometric evaluation was performed, the bladders were harvested and the degree of fibrosis was assessed. In another series of experiments mice deficient in the iNOS gene (iNOS −/−) were compared to WT mice for cystometric as well as histological changes in the bladder following partial bladder outlet obstruction or sham operation. Results: Partial bladder outlet obstruction induced the expression of iNOS mRNA in the mouse bladder. iNOS −/− mice showed a significantly smaller increase in bladder volume at 3 weeks compared with WT. Pharmacological inhibition of iNOS activity significantly attenuated the increase in bladder size and the number of spontaneous bladder contractions in obstructed rats at 2 weeks. Furthermore, genetic and pharmacological decreases in iNOS led to significantly less fibrosis of the bladder after partial bladder outlet obstruction in mice and rats, respectively. Conclusions: Pharmacological or genetic decreases in iNOS resulted in amelioration of functional and fibrotic changes in the bladder after partial bladder outlet obstruction, suggesting that NO contributes to the pathophysiology of bladder outlet obstruction. References 1 : Epidemiology, etiology, pathophysiology, and diagnosis of benign prostatic hyperplasia. In: . Philadelphia: W. B. Saunders Co.1998: 1429. chapt. 46. 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Google Scholar From the Center for Pediatric Urology and Laboratory for Minimally Invasive Urologic Surgery, Department of Urology, Children's Hospital of New York-Weill Medical College of Cornell University and Department of Pharmacology, Weill Medical College of Cornell University, New York, New York© 2003 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byJiang Y, Lee C and Kuo H (2016) Urothelial Dysfunction, Suburothelial Inflammation and Altered Sensory Protein Expression in Men with Bladder Outlet Obstruction and Various Bladder Dysfunctions: Correlation with UrodynamicsJournal of Urology, VOL. 196, NO. 3, (831-837), Online publication date: 1-Sep-2016.Tanaka S, Martinez-Ferrer M, Makari J, Wills M, Thomas J, Adams M, Brock J, Pope J and Bhowmick N (2009) Recruitment of Bone Marrow Derived Cells to the Bladder After Bladder Outlet ObstructionJournal of Urology, VOL. 182, NO. 4S, (1769-1774), Online publication date: 1-Oct-2009.Kawano K, Masuda H, Yano M, Kihara K, Sugimoto A and Azuma H (2018) Altered Nitric Oxide Synthase, Arginase and Ornithine Decarboxylase Activities, and Polyamine Synthesis in Response to Ischemia of the Rabbit DetrusorJournal of Urology, VOL. 176, NO. 1, (387-393), Online publication date: 1-Jul-2006. Volume 169Issue 4April 2003Page: 1569-1572 Advertisement Copyright & Permissions© 2003 by American Urological Association, Inc.Keywordsnitric-oxide synthasebladderrats, Sprague-Dawleybladder neck obstructionMetricsAuthor Information DIANE FELSEN Financial interest and/or other relationship with Promethean Surgical Devices. More articles by this author KAMBIZ DARDASHTI More articles by this author MICHAEL OSTAD More articles by this author MATTHEW L. LEMER More articles by this author STEVEN S. GROSS More articles by this author JIE CHEN More articles by this author E.D. VAUGHAN More articles by this author DIX P. POPPAS More articles by this author Expand All Advertisement PDF downloadLoading ...