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

Abstract

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.