Please use this identifier to cite or link to this item:
Type: Artigo de periódico
Title: The Soluble Guanylyl Cyclase Activator Bay 60-2770 Ameliorates Overactive Bladder In Obese Mice.
Author: Leiria, Luiz O
Silva, Fabio H
Davel, Ana Paula C
Alexandre, Eduardo C
Calixto, Marina C
De Nucci, Gilberto
Mónica, Fabíola Z
Antunes, Edson
Abstract: 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. 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. 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. 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.
Subject: Animals
Biphenyl Compounds
Blotting, Western
Enzyme Activators
Guanylate Cyclase
Hydrocarbons, Fluorinated
Lower Urinary Tract Symptoms
Mice, Inbred C57bl
Reactive Oxygen Species
Urinary Bladder, Overactive
Cyclic Guanosine Monophosphate
Low Density Lipoprotein
Lower Urinary Tract Symptoms
Nitric Oxide
Nonvoiding Contraction
Overactive Bladder
Reactive Oxygen Species
Soluble Guanylate Cyclase
Soluble Guanylyl Cyclase
Urinary Bladder
Citation: The Journal Of Urology. v. 191, n. 2, p. 539-47, 2014-Feb.
Rights: fechado
Identifier DOI: 10.1016/j.juro.2013.09.020
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

Files in This Item:
File SizeFormat 
24050894.pdf838.43 kBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.