Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/199575
Type: Artigo de periódico
Title: Long-term Oral Treatment With Bay 41-2272 Ameliorates Impaired Corpus Cavernosum Relaxations In A Nitric Oxide-deficient Rat Model.
Author: Claudino, Mário A
da Silva, Fabio H
Mónica, Fabíola Z T
Rojas-Moscoso, Julio A
De Nucci, Gilberto
Antunes, Edson
Abstract: • 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. • 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 α₁ -adrenoceptor agonist phenylephrine (PE) were obtained. • Acetylcholine (0.01-1000 µmol/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 µmol/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. • 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.
Subject: Animals
Cyclic Gmp
Enzyme Inhibitors
Erectile Dysfunction
Guanylate Cyclase
Male
Muscle Relaxants, Central
Ng-nitroarginine Methyl Ester
Nitric Oxide
Penile Erection
Pyrazoles
Pyridines
Rats
Rats, Wistar
Rights: fechado
Identifier DOI: 10.1111/j.1464-410X.2010.09776.x
Address: http://www.ncbi.nlm.nih.gov/pubmed/20950311
Date Issue: 2011
Appears in Collections:Unicamp - Artigos e Outros Documentos

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