Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)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 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.1081116122Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)