Inhibitors of phosphodiesterase 5 (PDE 5) inhibit the nerve‐induced release of nitric oxide from the rabbit corpus cavernosum

Background and purpose: Nitrergic neurons are important for erectile responses in the corpus cavernosum and impaired signalling results in erectile dysfunction, today treated successfully by oral administration of the selective phosphodiesterase 5 (PDE 5) inhibitors sildenafil, tadalafil and vardenafil. Although the importance of nitrergic neurons in urogenital function has become evident, it has not been investigated if the PDE 5 inhibitors affect the nerve-induced release of nitric oxide (NO). In a previous study we found that the soluble guanylate cyclase (sGC)/cyclic guanosine 3’,5’–monophosphate (cGMP) pathway might modulate nerve-induced release of NO in isolated cavernous tissue. Experimental approach: Electrical field stimulation (EFS 5 Hz, 40 V, 0.3 ms pulse duration, 25 pulses at intervals of 2 min) of rabbit isolated cavernous tissue elicited reproducible, nerve-mediated relaxations in the presence of scopolamine (10 � 5 M), guanethidine (10 � 5 M) and phenylephrine (3 � 10 � 6 M). In superfusion experiments, nerve stimulation (20 Hz, 40 V, 1 ms) of the cavernous tissue evoked release of NO/NO2 , measured by chemiluminescence. Key results: Sildenafil, tadalafil and vardenafil decreased the muscular tone and prolonged the relaxations to nerve stimulation. The evoked release of NO decreased to 72711%, 55716% and 61714% of control, respectively after addition of