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• W2022704613 abstract "No AccessJournal of UrologyInvestigative Urology1 Feb 2014The Soluble Guanylyl Cyclase Activator BAY 60-2770 Ameliorates Overactive Bladder in Obese Mice Luiz O. Leiria, Fabio H. Silva, Ana Paula C. Davel, Eduardo C. Alexandre, Marina C. Calixto, Gilberto De Nucci, Fabíola Z. Mónica, and Edson Antunes Luiz O. LeiriaLuiz O. Leiria More articles by this author , Fabio H. SilvaFabio H. Silva More articles by this author , Ana Paula C. DavelAna Paula C. Davel More articles by this author , Eduardo C. AlexandreEduardo C. Alexandre More articles by this author , Marina C. CalixtoMarina C. Calixto More articles by this author , Gilberto De NucciGilberto De Nucci More articles by this author , Fabíola Z. MónicaFabíola Z. Mónica More articles by this author , and Edson AntunesEdson Antunes More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.09.020AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Activators of soluble guanylyl cyclase are of potential interest as treatment for cardiovascular diseases but to our knowledge they have never been proposed to treat overactive bladder. We evaluated the effects of the soluble guanylyl cyclase activator BAY 60-2270 on voiding dysfunction and detrusor overactivity in a mouse model of obesity associated overactive bladder. Materials and Methods: C57BL/6 male mice fed for 10 weeks with standard chow or a high fat diet were treated with 1 mg/kg BAY 60-2770 per day for 2 weeks via gavage. Cystometric evaluations were done and responses to contractile agents in isolated bladders were determined. Results: Obese mice showed an irregular micturition pattern characterized by significant increases in voiding and nonvoiding contractions, which were normalized by BAY 60-2770. Carbachol, KCl and CaCl2 produced concentration dependent contractions in isolated bladder strips, which were markedly greater in obese than in lean mice. BAY 60-2770 normalized bladder contractions in the obese group. A 78% increase in reactive oxygen species generation in the bladder tissue of obese mice was observed, which was unaffected by BAY 60-2770. Treatment with BAY 60-2770 generated a tenfold increase in cyclic guanosine monophosphate in the bladders of obese mice without affecting the nucleotide level in the lean group. Protein expression of the soluble guanylyl cyclase α1 and β1 subunits was decreased 40% in the bladder tissue of obese mice but restored by BAY 60-2770. Conclusions: Two-week BAY 60-2770 therapy increased cyclic guanosine monophosphate and rescued expression of the soluble guanylyl cyclase α1 and β1 subunits in bladder tissue, resulting in great amelioration of bladder dysfunction. References 1 : The impact of obesity on urinary incontinence symptoms, severity, urodynamic characteristics and quality of life. J Urol2010; 183: 622. Link, Google Scholar 2 : Alterations of M2,3-muscarinic receptor protein and mRNA expression in the bladder of the fructose fed obese rat. J Urol2007; 178: 1537. Link, Google Scholar 3 : Pathophysiological studies of overactive bladder and bladder motor dysfunction in a rat model of metabolic syndrome. J Urol2011; 186: 318. Link, Google Scholar 4 : An animal model to study lower urinary tract and erectile dysfunction: the hyperlipidaemic rat. BJU Int2007; 100: 658. Google Scholar 5 : Role of PKC and CaV1.2 in detrusor overactivity in a model of obesity associated with insulin resistance in mice. 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Link, Google Scholar 29 : Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals. Clin Chem2011; 57: 1524. Google Scholar 30 : Selective β3-adrenoceptor agonists in the treatment of the overactive bladder. J Urol2013; 190: 1173. Link, Google Scholar © 2014 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byWein A (2019) Re: Oxidative Stress and its Possible Relation to Lower Urinary Tract Functional PathologyJournal of Urology, VOL. 201, NO. 6, (1058-1059), Online publication date: 1-Jun-2019. Volume 191Issue 2February 2014Page: 539-547 Advertisement Copyright & Permissions© 2014 by American Urological Association Education and Research, Inc.Keywordsobesitysoluble guanylyl cyclaselower urinary tract symptomsurinary bladderoveractivereactive oxygen speciesMetricsAuthor Information Luiz O. Leiria More articles by this author Fabio H. Silva More articles by this author Ana Paula C. Davel More articles by this author Eduardo C. Alexandre More articles by this author Marina C. Calixto More articles by this author Gilberto De Nucci More articles by this author Fabíola Z. Mónica More articles by this author Edson Antunes More articles by this author Expand All Advertisement PDF downloadLoading ..." @default.
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