Administration of BAY 41-2272 prevents bladder dysfunction in nitric-oxide deficient rats

• Main Authors: Carlos Arturo Levi D’Ancona, Fabíola Zakia Taufic Mónica, Ricardo Reges, David Cohen, Fabio Henrique da Silva, Gilberto De Nucci, Edson Antunes
• Format: Article
• Language: English
• Published: Instituto Israelita de Ensino e Pesquisa Albert Einstein 2010-12-01
• Series: Einstein (São Paulo)
• Subjects: Guanylate cyclase; Nitric oxide; Urinary bladder; overactive; Rats
• Online Access: http://apps.einstein.br/revista/arquivos/PDF/1789-Einsteinv8n4_pg404-409_eng.pdf

Objective: to evaluate the protective effects of BAY 41-2272, asoluble guanylate cyclase activator, on changes in cystometricparameters in rats deficient in nitric oxide (NO). Methods: Ratswere divided into the following groups: (a) control; (b) DMSO; (c)L-NAME; (d) BAY 41-2272 alone; (e) L-NAME + BAY 41-2272.The NO synthase blocker L-NAME (20 mg/rat/day) was given indrinking water concomitantly or not with BAY 41-2272 (10 mg/kg/day, given by gavage). Results: Chronic L-NAME treatmentmarkedly increased the mean arterial blood pressure, and cotreatmentwith BAY 41-2272 nearly reversed L-NAME-inducedrise on mean arterial blood pressure. Non-void contractions weresignificantly increased in L-NAME group (0.90 ± 0.1 number/minute) compared with either DMSO or control group (0.49 ± 0.1number/minute), which were prevented by co-treatment with BAY41-2272 (0.56 ± 025 number/minute; p < 0.05). The thresholdand peak pressure increased by 70 and 44%, respectively, afterchronic L-NAME treatment, while co-treatment with BAY 41-2272largely attenuated both 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, andco-treatment with BAY 41-2272 normalized this parameter.Conclusions: Our data show that long-term oral administrationof BAY 41-2272 counteracts the bladder dysfunction seen inNO-deficient rats, indicating that restoration of the NO-cGMPpathway by this compound may be of beneficial value to treatbladder symptoms.