Reduction of obstruction related bladder overactivity by the guanylyl cyclase modulators BAY 41-2272 and BAY 60-2770 alone or in combination with a phosphodiesterase type 5 inhibitor

• Published in: Neurourology and urodynamics 2015-11, Vol.34 (8), p.787-793
• Main Authors: Füllhase, C., Hennenberg, M., Sandner, P., Strittmatter, F., Niedworok, C., Bauer, R.M., Gratzke, C., Soler, R., Stief, C., Andersson, K.E.
• Format: Article
• Language: English
• Subjects: Animals; Benzoates - pharmacology; Benzoates - therapeutic use; Biphenyl Compounds - pharmacology; Biphenyl Compounds - therapeutic use; Cyclic GMP - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 5 - metabolism; Disease Models, Animal; Drug Therapy, Combination; Guanylate Cyclase - metabolism; Hydrocarbons, Fluorinated - pharmacology; Hydrocarbons, Fluorinated - therapeutic use; lower urinary tract symptoms; Male; Phosphodiesterase 5 Inhibitors - pharmacology; Phosphodiesterase 5 Inhibitors - therapeutic use; phosphodiesterase type 5 inhibitors; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Pyridines - pharmacology; Pyridines - therapeutic use; Rats; Rats, Sprague-Dawley; soluble guanylyl cyclase; Urethral Obstruction - complications; Urethral Obstruction - drug therapy; Urethral Obstruction - metabolism; Urinary Bladder - drug effects; Urinary Bladder - metabolism; urinary bladder diseases; Urinary Bladder, Overactive - drug therapy; Urinary Bladder, Overactive - etiology; Urinary Bladder, Overactive - metabolism; urodynamics
• ISSN: 0733-2467; 1520-6777
• DOI: 10.1002/nau.22665

Aims To assess the urodynamic effects of soluble guanylyl cyclase (sGC) stimulator, BAY 41‐2272, and activator, BAY 60‐2770, (which both are able to induce cGMP synthesis even in the absence of nitric oxide (NO)) alone or in combination with a phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, in a model of partial urethral obstruction (PUO) induced bladder overactivity (BO). Methods Fifty‐six male Sprague–Dawley rats were used, 31 of them underwent PUO. Fourteen rats were used for Western blots to assess PDE5 and sGC expression. For drug evaluation cystometry without anesthesia was performed three days following bladder catheterization. Results Obstructed rats showed higher micturition frequency and bladder pressures than non‐obstructed animals (Intermicturition Interval, IMI, 2.28 ± 0.55 vs. 3.60 ± 0.60 min (± standard deviation, SD); maximum micturition pressure, MMP, 70.1 ± 8.0 vs. 48.8 ± 7.2 cmH2O; both P