Abstract
BackgroundRadical prostatectomy (RP) is frequently responsible for erectile dysfunction (ED). Post-RP patients often show a failure to respond to phosphodiesterase type 5 (PDE5) inhibitors. ObjectiveThe acute effect of BAY 60-4552, the soluble guanylate cyclase (sGC) stimulator, and vardenafil were evaluated alone or in combination on erectile responses to electrical stimulation of the cavernous nerve (ES CN) in rats with cavernous nerve (CN) crush injury–induced ED. Design, setting, and participantsMale adult Sprague-Dawley rats underwent laparotomy (sham, n=10) or bilateral CN crush injury (n=56). After 3 wk of recovery, erectile function was evaluated under urethane anaesthesia following ES CN at different frequencies. MeasurementsThe acute effects of intravenous (IV) injection of vehicle, vardenafil 0.03mg/kg, BAY 60-4552 0.03mg/kg or 0.3mg/kg, or a BAY 60-4552 0.03mg/kg plus vardenafil 0.03mg/kg combination were evaluated in CN-crushed rats. Results and limitationsBilateral CN crush injury followed by a 3-wk recovery period decreased erectile responses to ES CN by about 50%. In CN-crushed rats, IV vardenafil 0.03mg/kg and BAY 60-4552 (0.03 or 0.3mg/kg) increased erectile responses to ES CN to the same extent: Δ intracavernosal pressure/mean arterial pressure (ICP/MAP) at 10Hz ES CN was 21±1% after vehicle, 25±3% (p<0.001) after vardenafil, and 26±5% and 27±5% after BAY 60-4552 0.03mg/kg (p<0.01) and 0.3mg/kg (p<0.001), respectively. The combination of vardenafil with BAY 60-4552 in CN-crushed rats totally restored erectile responses to ES CN equivalent to sham rats (ΔICP/MAP at 10Hz ES CN: 34±4% after BAY 60-4552/vardenafil combination vs 39±4% in sham rats; not significant). ConclusionsThe present study supports the concept that the combined administration of a sGC stimulator, BAY 60-4552, and vardenafil provides synergistic beneficial effects and might therefore salvage patients who experience treatment failures with PDE5 inhibitors after RP.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.