Long-term oral treatment with BAY 41-2272 ameliorates impaired corpus cavernosum relaxations in a nitric oxide-deficient rat model

dc.creatorClaudino, MA
dc.creatorda Silva, FH
dc.creatorMonica, FZT
dc.creatorRojas-Moscoso, JA
dc.creatorDe Nucci, G
dc.creatorAntunes, E
dc.date2011
dc.dateJUL
dc.date2014-07-30T13:38:53Z
dc.date2015-11-26T16:29:39Z
dc.date2014-07-30T13:38:53Z
dc.date2015-11-26T16:29:39Z
dc.date.accessioned2018-03-28T23:10:42Z
dc.date.available2018-03-28T23:10:42Z
dc.identifierBju International. Wiley-blackwell, v. 108, n. 1, n. 116, n. 122, 2011.
dc.identifier1464-4096
dc.identifierWOS:000291928500025
dc.identifier10.1111/j.1464-410X.2010.09776.x
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/52637
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/52637
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1269779
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionOBJECTIVE To investigate the potential beneficial effects of 4-week oral treatment with 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1Hpyrazolo[3,4-b]pyridin-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a nitric oxide (NO)independent soluble guanylate cyclase activator, on impaired rat corpus cavernosum relaxations in NO-deficient rats. MATERIAL AND METHODS Male Wistar rats were divided into four groups: Control, N (G)-nitro-L-arginine methyl ester (L-NAME; 20 mg/rat/day), BAY 41-2272 (20 mg/kg/day) and L-NAME + BAY 41-2272. Rats were treated with L-NAME concomitantly with BAY 41-2272 for 4 weeks. Concentration-response curves to acetylcholine (ACh) and sodium nitroprusside (SNP), along with the nitrergic relaxations (1-32 Hz) were obtained in rat corpus cavernosum (RaCC). The RaCC contractile responses to the alpha(1)-adrenoceptor agonist phenylephrine (PE) were obtained. RESULTS Acetylcholine (0.01-1000 mu mol/L) produced concentration-dependent relaxing responses in RaCC that were significantly enhanced (P < 0.05) in BAY 41-2272-treated rats. The ACh-induced relaxations were largely reduced in L-NAME-treated rats, and co-treatment with BAY 41-2272 failed to significantly modify these impaired relaxations. The SNP-induced relaxations were modified neither by L-NAME nor by co-treatment with BAY 41-2272. The nitrergic relaxations were significantly amplified in BAY 41-2272-treated rats (at 16 and 32 Hz). A significant reduction in the nitrergic relaxations was observed in L-NAME-treated rats, an effect largely restored by co-treatment with BAY 41-2272. The contractile RaCC responses produced by PE (0.001-100 mu mol/L) were significantly higher (P < 0.05) in L-NAME-treated rats, and co-treatment of L-NAME with BAY 41-2272 nearly restored these enhanced contractile responses. CONCLUSION Four-week therapy with BAY 41-2272 prevents the impaired corpus cavernosum relaxations of rats treated chronically with L-NAME, indicating that accumulation of cyclic guanosine monophosphate into erectile tissue counteracts the NO deficiency.
dc.description108
dc.description1
dc.description116
dc.description122
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.languageen
dc.publisherWiley-blackwell
dc.publisherMalden
dc.publisherEUA
dc.relationBju International
dc.relationBJU Int.
dc.rightsfechado
dc.rightshttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.sourceWeb of Science
dc.subjectBAY 41-2272
dc.subjecterectile dysfunction
dc.subjectsoluble guanylyl cyclase
dc.subjecterection
dc.subjectSoluble-guanylate-cyclase
dc.subjectNo-independent Stimulators
dc.subjectCyclic-gmp Formation
dc.subjectErectile Dysfunction
dc.subjectPenile Erection
dc.subjectChronic Inhibition
dc.subjectSmooth-muscle
dc.subjectRelaxes Human
dc.subjectBay-41-2272
dc.subjectHypertension
dc.titleLong-term oral treatment with BAY 41-2272 ameliorates impaired corpus cavernosum relaxations in a nitric oxide-deficient rat model
dc.typeArtículos de revistas


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