We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Long-term oral treatment with BAY 41-2272 ameliorates impaired corpus cavernosum relaxations in a nitric oxide-deficient rat model.
- Authors
Claudino, Mário A.; da Silva, Fabio H.; Mónica, Fabíola Z. T.; Rojas-Moscoso, Julio A.; De Nucci, Gilberto; Antunes, Edson
- Abstract
OBJECTIVE: • 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 α1-adrenoceptor agonist phenylephrine (PE) were obtained. RESULTS • 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 cotreatment with BAY 41-2272 failed to significantly modify these impaired relaxations. • The SNP-induced relaxations were modified neither by L-NAME nor by cotreatment 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 LNAME- 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. CONCLUSION: • Four-week therapy with BAY 41-2272 prevents the impaired corpus cavernosum relaxations of rats treated chronically with LNAME, indicating that accumulation of cyclic guanosine monophosphate into erectile tissue counteracts the NO deficiency.
- Subjects
ORAL medicine; GUANYLATE cyclase; NITRIC oxide; IMPOTENCE; PENILE erection; LABORATORY mice
- Publication
BJU International, 2011, Vol 108, Issue 1, p116
- ISSN
1464-4096
- Publication type
Article
- DOI
10.1111/j.1464-410X.2010.09776.x