Long-term administration of BAY 41-2272 prevents bladder dysfunction in nitric oxide-deficient rats

Chronic blockade of nitric oxide (NO) synthesis leads to detrusor smooth muscle overactivity. This study aimed to evaluate the protective effects of BAY 41-2272, a soluble guanlylate cyclase activator, on changes in cystometric parameters in NO-deficient rats.

Rats were divided into the following groups: (a) control, (b) DMSO, (c) N(ω)-nitro-L-arginine methyl ester hydrochrolide (L-NAME), (d) BAY 41-2272 alone, and (e) L-NAME + BAY 41-2272. The NO synthase blocker L-NAME (20 mg/rat/day) was giving in the drinking water concomitantly or not with BAY 41-2272 (10 mg/kg/day, given by gavage).

Chronic L-NAME treatment markedly increased the mean arterial blood pressure (MABP), and co-treatment with BAY 41-2272 nearly reversed L-NAME-induced rise on MABP. Non-void contractions were significantly increased in L-NAME group (0.90 ± 0.1 number/min) compared with either DMSO or control group (0.49 ± 0.1 number/min), which were prevented by co-treatment with BAY 41-2271 (0.56 ± 025 number/min; P < 0.05). The threshold pressure and peak pressure increased by 70% and 44% after chronic L-NAME treatment, while co-treatment with BAY 41-2272 largely attenuated both of these effects (27% and 22% increase, respectively). The frequency of micturition cycles decreased by about of 50% in L-NAME-treated rats compared with control animals, and co-treatment with BAY 41-2272 normalized this parameter.

Our data show that long-term oral administration of BAY 41-2272 counteracts the bladder dysfunction seen in NO-deficient rats, indicating that restoration of the NO-cGMP pathway by this compound may be of beneficial value to treat bladder symptoms.