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• W2067645503 abstract "No AccessJournal of UrologyInvestigative Urology1 Feb 2005ALTERED INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSION AND NITRIC OXIDE PRODUCTION IN THE BLADDER OF CATS WITH FELINE INTERSTITIAL CYSTITIS L.A. BIRDER, A. WOLF-JOHNSTON, C.A. BUFFINGTON, J.R. ROPPOLO, W.C. de GROAT, and A.J. KANAI L.A. BIRDERL.A. BIRDER Financial interest and/or other relationship with Roche Palo Alto. More articles by this author , A. WOLF-JOHNSTONA. WOLF-JOHNSTON More articles by this author , C.A. BUFFINGTONC.A. BUFFINGTON More articles by this author , J.R. ROPPOLOJ.R. ROPPOLO More articles by this author , W.C. de GROATW.C. de GROAT Financial interest and/or other relationship with Abbott Pharmaceuticals, Roche Palo Alto, Eli Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Dynagen, Novartis Pharmaceuticals, Urogene, Johnson and Johnson, Newron, ICOS and Neurogen. More articles by this author , and A.J. KANAIA.J. KANAI More articles by this author View All Author Informationhttps://doi.org/10.1097/01.ju.0000145900.22849.1dAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Alterations in nitric oxide (NO) levels have been demonstrated in some humans with interstitial cystitis (IC) as well as in chemically induced animal models of cystitis. Thus, in the current study we investigated whether inducible NO synthase (iNOS) mediated NO production is altered in the bladder of cats with a naturally occurring model of IC termed feline IC (FIC). Materials and Methods: We examined iNOS expression using Western immunoblotting and baseline NO production using an NO microsensor from smooth muscle and mucosal bladder strips in 9 healthy cats and 6 diagnosed with FIC. Results: There was a significant increase in baseline NO production in cats with FIC compared with that in healthy cats in smooth muscle and mucosal strips. This production was not ablated in the absence of extracellular Ca2+ (100 μM egtazic acid) or following incubation with the calmodulin antagonist trifluoroperazine (20 μM), indicating iNOS mediated Ca2+ independent NO production. Release was significantly decreased following incubation with the NOS antagonist L-NAME (N-nitro-L-arginine methyl ester) (100 μM). Furthermore, immunoblotting revealed a trend toward increased iNOS expression in smooth muscle and mucosal strips from FIC cats but not from healthy cats. Conclusions: In light of previous findings that the barrier property of the urothelial surface is disrupted in FIC and iNOS mediated increase in NO alters barrier function in other types of epithelium our findings suggest that iNOS dependent NO production may have a role in epithelial barrier dysfunction in FIC. References 1 : Editorial: interstitial cystitis—an elusive target?. J Urol2003; 170: 816. Link, Google Scholar 2 : Recent developments in the management of interstitial cystitis. Curr Opin Urol2003; 13: 309. Google Scholar 3 : Feline interstitial cystitis. J Am Vet Med Assoc1999; 215: 682. Google Scholar 4 : Urothelial pathophysiological changes in feline interstitial cystitis: a human model. Am J Physiol2000; 278: F540. Google Scholar 5 : Beta-adrenergic agonists stimulate endothelial nitric oxide synthase in rat urinary bladder urothelial cells. J Neurosci2002; 22: 8063. Google Scholar 6 : Nitric oxide in the lower urinary tract: physiological and pathological implications. BJU Int2000; 85: 567. Google Scholar 7 : Nitric oxide directly impairs intestinal barrier function. Shock2002; 17: 139. Google Scholar 8 : Urine markers of interstitial cystitis. Urology2001; 57: 15. Google Scholar 9 : Intravesical nitric oxide production discriminates between classic and nonulcer interstitial cystitis. J Urol2004; 171: 1148. Link, Google Scholar 10 : Alterations in bladder afferent neurons and urothelium in feline interstitial cystitis. Soc Neurosci Abstr2000; 26: 930. Google Scholar 11 : Isolation of nitric oxide synthase, a calmodulin-requiring enzyme. Proc Natl Acad Sci USA1990; 87: 682. Google Scholar 12 : Improvement in interstitial cystitis symptoms scores during treatment with oral L-arginine. J Urol1997; 158: 703. Link, Google Scholar 13 : The physiological expression of inducible nitric oxide synthase (iNOS) in the human colon. J Clin Pathol2001; 54: 293. Google Scholar 14 : Increased iNOS activity is essential for intestinal epithelial tight junction dysfunction in endotoxemic mice. Shock2004; 21: 261. Google Scholar 15 : Effect of intravesical nitric oxide therapy on cyclophosphamide-induced cystitis. J Urol1999; 162: 2211. Link, Google Scholar 16 : Involvement of nitric oxide (NO) in bladder afferent and urothelial abnormalities following chronic spinal cord injury. Soc Neurosci Abstr2001; 27. abstract 842.9. Google Scholar 17 : Inverse expression of uroplakins and inducible nitric oxide synthase in the urothelium of patients with bladder outlet obstruction. BJU Int2003; 91: 507. Google Scholar 18 : Expression of inducible nitric oxide synthase in primary culture of rat bladder smooth muscle cells by plasma from cyclophosphamide-treated rats. Eur J Pharmacol2001; 416: 1. Google Scholar 19 : Activity and expression of nitric oxide synthase in the hypertrophied rat bladder and the effect of nitric oxide on bladder smooth muscle growth. J Urol2002; 168: 2689. Link, Google Scholar 20 : Lipopolysaccharide and inflammatory cytokines cause an inducible nitric oxide synthase dependent bladder smooth muscle fibrotic response. J Urol2003; 170: 645. Link, Google Scholar From the Departments of Medicine (LAB, AW-J, AJK) and Pharmacology (LAB, JRR, WCdG, AJK), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, and Department of Clinical Veterinary Sciences (CAB), Ohio State University, Columbus, Ohio© 2005 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byIkeda Y, Birder L, Buffington C, Roppolo J and Kanai A (2009) Mucosal Muscarinic Receptors Enhance Bladder Activity in Cats With Feline Interstitial CystitisJournal of Urology, VOL. 181, NO. 3, (1415-1422), Online publication date: 1-Mar-2009. Volume 173Issue 2February 2005Page: 625-629 Advertisement Copyright & Permissions© 2005 by American Urological Association, Inc.Keywordscatsurotheliumnitric oxidecystitis, interstitialbladderMetricsAuthor Information L.A. BIRDER Financial interest and/or other relationship with Roche Palo Alto. More articles by this author A. WOLF-JOHNSTON More articles by this author C.A. BUFFINGTON More articles by this author J.R. ROPPOLO More articles by this author W.C. de GROAT Financial interest and/or other relationship with Abbott Pharmaceuticals, Roche Palo Alto, Eli Lilly Pharmaceuticals, Pfizer Pharmaceuticals, Dynagen, Novartis Pharmaceuticals, Urogene, Johnson and Johnson, Newron, ICOS and Neurogen. More articles by this author A.J. KANAI More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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