Experimental evidence that a combination of sGC stimulator BAY 60-4552 and PDE5 inhibitor vardenafil could salvage ED-patients with insufficient response to PDE5 inhibitors after cavernous nerve injury
© Oudot et al; licensee BioMed Central Ltd. 2011
Published: 1 August 2011
Radical prostatectomy (RP) is frequently responsible for erectile dysfunction (ED). Post-RP patients often show insufficient response or treatment failures to PDE5 inhibitor therapy. This study was undertaken to evaluate the acute effects of the soluble guanylate cyclase (sGC) stimulator, BAY 60-4552 and vardenafil administered 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 and methods
Male Sprague-Dawley rats underwent laparotomy (sham, n=10) or bilateral CN crush injury (n=57). After 3 weeks of recovery, erectile function was evaluated in urethane-anesthetized rats following ES-CN at different frequencies. The acute effects of intravenous (iv) injection of vehicle, vardenafil 0.03 mg/kg, BAY 60-4552 0.03 mg/kg or 0.3 mg/kg, or a BAY 60-4552 0.03 mg/kg + vardenafil 0.03 mg/kg combination were evaluated in CN crushed rats.
Bilateral CN crush injury followed by a 3-week recovery period decreased erectile responses to ES-CN by about 50%. In CN crushed rats, both iv vardenafil 0.03 mg/kg and BAY 60-4552 at the tested dosings (0.03 or 0.3 mg/kg) increased erectile responses to ES-CN to the same extent: ΔICP/MAP at 10Hz ES-CN was 20.9± 1.3 % after iv vehicle, 25.3± 3.3 % (P<0.001) after iv vardenafil, and 26.3± 4.9 % and 26.6± 5.2 % after BAY 60-4552 0.03 mg/kg (P<0.01) and 0.3 mg/kg (P<0.001) respectively. The combined iv administration of vardenafil and BAY 60-4552 in CN crushed rats exerted additive effects and totally restored erectile responses to ES-CN equivalent to sham rats (ΔICP/MAP at 10Hz ES-CN : 34.0± 4.4 % after BAY 60-4552/vardenafil combination vs 39.2± 3.7 % in sham rats, ns).
The present study supports the concept that the combined administration of a sGC stimulator, BAY 60-4552 and vardenafil provides additive beneficial effects. Thus this combination could become a novel treatment option in ED patients with cavernous nerve injury showing insufficient response or treatment failures to PDE5 inhibitors.
This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.