BAY 41-2272, a Soluble Guanylate Cyclase Stimulator, Relaxes Isolated Human Ureter in a Standardized In Vitro Model

dc.creatorMiyaoka, R
dc.creatorMendes, C
dc.creatorSchenka, A
dc.creatorGonzalez, PG
dc.creatorde Nucci, G
dc.creatorAntunes, E
dc.creatorMonga, M
dc.creatorD'Ancona, CAL
dc.creatorMonica, FZ
dc.date2014
dc.dateJAN
dc.date2014-07-30T13:51:43Z
dc.date2015-11-26T16:41:02Z
dc.date2014-07-30T13:51:43Z
dc.date2015-11-26T16:41:02Z
dc.date.accessioned2018-03-28T23:25:08Z
dc.date.available2018-03-28T23:25:08Z
dc.identifierUrology. Elsevier Science Inc, v. 83, n. 1, 2014.
dc.identifier0090-4295
dc.identifier1527-9995
dc.identifierWOS:000328695800070
dc.identifier10.1016/j.urology.2013.09.005
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/55346
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/55346
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1272798
dc.descriptionOBJECTIVE To characterize the relaxation induced by BAY 41-2272 in human ureteral segments. MATERIALS AND METHODS Ureter specimens (n = 17) from multiple organ human deceased donors (mean age 40 +/- 3.2 years, male/female ratio 2: 1) were used to characterize the relaxing response of BAY 41-2272. Immunohistochemical analysis for endothelial and neuronal nitric oxide synthase, guanylate cyclase stimulator (sGC) and type 5 phosphodiesterase was also performed. The potency values were determined as the negative log of the molar to produce 50% of the maximal relaxation in potassium chloride-precontracted specimens. The unpaired Student t test was used for the comparisons. RESULTS Immunohistochemistry revealed the presence of endothelial nitric oxide synthase in vessel endothelia and neuronal nitric oxide synthase in urothelium and nerve structures. sGC was expressed in the smooth muscle and urothelium layer, and type 5 phosphodiesterase was present in the smooth muscle only. BAY 41-2272 (0.001-100 mu M) relaxed the isolated ureter in a concentration dependent manner, with a potency and maximal relaxation value of 5.82 +/- 0.14 and 84% +/- 5%, respectively. The addition of nitric oxide synthase and sGC inhibitors reduced the maximal relaxation values by 21% and 45%, respectively. However, the presence of sildenafil (100 nM) significantly potentiated (6.47 +/- 0.10, P <. 05) this response. Neither glibenclamide or tetraethylammonium nor ureteral urothelium removal influenced the relaxation response by BAY 41-2272. CONCLUSION BAY 41-2272 relaxes the human isolated ureter in a concentration-dependent manner, mainly by activating the sGC enzyme in smooth muscle cells rather than in the urothelium, although a cyclic guanosine monophosphate-independent mechanism might have a role. The potassium channels do not seem to be involved. UROLOGY 83: 256.e1-256.e7, 2014. (C) 2014 Elsevier Inc.
dc.description83
dc.description1
dc.languageen
dc.publisherElsevier Science Inc
dc.publisherNew York
dc.publisherEUA
dc.relationUrology
dc.relationUrology
dc.rightsfechado
dc.rightshttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.sourceWeb of Science
dc.subjectNitric-oxide Synthase
dc.subjectSmooth-muscle
dc.subjectUrinary-tract
dc.subjectPeristalsis
dc.subjectBladder
dc.subjectBay-41-2272
dc.subjectMechanisms
dc.subjectActivators
dc.subjectArtery
dc.subjectCells
dc.titleBAY 41-2272, a Soluble Guanylate Cyclase Stimulator, Relaxes Isolated Human Ureter in a Standardized In Vitro Model
dc.typeArtículos de revistas


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