The Soluble Guanylyl Cyclase Activator Bay 60-2770 Ameliorates Overactive Bladder In Obese Mice.

dc.creatorLeiria, Luiz O
dc.creatorSilva, Fabio H
dc.creatorDavel, Ana Paula C
dc.creatorAlexandre, Eduardo C
dc.creatorCalixto, Marina C
dc.creatorDe Nucci, Gilberto
dc.creatorMónica, Fabíola Z
dc.creatorAntunes, Edson
dc.date2014-Feb
dc.date2015-11-27T13:42:15Z
dc.date2015-11-27T13:42:15Z
dc.date.accessioned2018-03-29T01:20:19Z
dc.date.available2018-03-29T01:20:19Z
dc.identifierThe Journal Of Urology. v. 191, n. 2, p. 539-47, 2014-Feb.
dc.identifier1527-3792
dc.identifier10.1016/j.juro.2013.09.020
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/24050894
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/201287
dc.identifier24050894
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1301520
dc.descriptionActivators 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.
dc.description191
dc.description539-47
dc.languageeng
dc.relationThe Journal Of Urology
dc.relationJ. Urol.
dc.rightsfechado
dc.rightsCopyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
dc.sourcePubMed
dc.subjectAnimals
dc.subjectBenzoates
dc.subjectBiphenyl Compounds
dc.subjectBlotting, Western
dc.subjectEnzyme Activators
dc.subjectGuanylate Cyclase
dc.subjectHydrocarbons, Fluorinated
dc.subjectLower Urinary Tract Symptoms
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred C57bl
dc.subjectObesity
dc.subjectReactive Oxygen Species
dc.subjectUrinary Bladder, Overactive
dc.subjectLdl
dc.subjectNo
dc.subjectNvc
dc.subjectOab
dc.subjectRos
dc.subjectCgmp
dc.subjectCyclic Guanosine Monophosphate
dc.subjectLow Density Lipoprotein
dc.subjectLower Urinary Tract Symptoms
dc.subjectNitric Oxide
dc.subjectNonvoiding Contraction
dc.subjectObesity
dc.subjectOveractive
dc.subjectOveractive Bladder
dc.subjectReactive Oxygen Species
dc.subjectSgc
dc.subjectSoluble Guanylate Cyclase
dc.subjectSoluble Guanylyl Cyclase
dc.subjectUrinary Bladder
dc.titleThe Soluble Guanylyl Cyclase Activator Bay 60-2770 Ameliorates Overactive Bladder In Obese Mice.
dc.typeArtículos de revistas


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