Effect of sildenafil administration on penile hypoxia induced by cavernous neurotomy in the rat

Abstract

Hypoxia is a normal, physiological condition in penile tissue, which is interrupted by reoxygenation associated to sleep-related erections. We previously described in the rat that a penile fibrosis and overexpression of the pro-fibrotic endothelin-1 type B receptor (ETB) are associated to prolonged (3 months) hypoxia induced by the bilateral surgical resection of the cavernous nerves (bilateral cavernous neurotomy (BCN)). The aim of the present study was to define the time frame in which BCN induces hypoxia and ETB overexpression in the penile tissue. In addition, we studied the timedependency of the rescuing effect of an acute administration of the phosphodiesterase type 5 inhibitor, sildenafil. We found that BCN induced penile hypo-oxygenation (immunohistochemistry for Hypoxyprobe), penile ETB mRNA overexpression (quantitative real-time reverse transcriptase polymerase chain reaction) and hypersensitivity to the ETB agonist IRL-1620 (in vitro contractility study). Sildenafil treatment was able to counteract all these alterations (penile hypoxygenation, hyper-sensitivity to IRL-1620 and ETB overexpression), with its effect being more evident the earlier it was administered.

Prophylaxis of Erectile Function After Radical Prostatectomy with Phosphodiesterase Type 5 Inhibitors

“…They found that chronic tadalafil treatment almost completely restored penile oxygenation and the ratio of smooth muscle and fibrous tissue at histology. Similar results were obtained by the same group using sildenafil and vardenafil [45,46]. In a very recent report, Lysiak and colleagues demonstrated a protective role of chronic tadalafil administration on mice subjected to cavernous nerve resection or sham surgery [47].…”

Increased cyclic guanosine monophosphate production and endothelial nitric oxide synthase level in mononuclear cells from sildenafil citrate-treated patients with erectile dysfunction

“…However, in a recent clinical study Montorsi et al 40 proposed that on-demand vardenafil treatment is the best option for the treatment of ED in men after bilateral Sildenafil citrate and mononuclear cells J García-Cardoso et al nerve-sparing radical prostatectomy with respect to daily administration. Similar results were also recently obtained by Vignozzi et al 41 in a rat experimental model of penile hypoxia showing that PDE5 inhibitors treatment should be started as soon as possible. This study only compared the effect of one and two sildenafil citrate doses on the NO/cGMP system in mononuclear cells, so we cannot rule out the possibility that the use of sildenafil citrate on a daily basis may exerts additional effects on the levels of the proteins involved in the NO/cGMP system in mononuclear cells, which should be further studied.…”

Penile rehabilitation therapy following radical prostatectomy

“…PDE-5s seem to prevent the endothelial damage related to ischaemia-reperfusion and denervation [14,15]. Furthermore, recent studies underline the use of sildenafil after RP to be associated with preservation of smooth-muscle content within the corpora cavernosa [15][16][17]. The natural recovery of EF seems to take place as long as 24 months and the early institution of medical therapy, specifically intracorporal injections, after 2 months post-operatively has resulted in a higher incidence of spontaneous return of erections at 1 year [2].…”