Effect of sildenafil on non-adrenergic non-cholinergic neurotransmission in bovine penile small arteries.

The purpose of the present study was to investigate the effect of the phosphodiesterase isoenzyme V inhibitor, sildenafil, on non-adrenergic non-cholinergic neurogenic relaxations of intracavernous isolated penile small arteries. Dense plexes of nerve fibres immunoreactive for neural nitric oxide (NO) synthase were observed in the adventitia-media junction of the penile small arteries. In 5-hydroxytryptamine-contracted preparations, the inhibitor of NO synthase, N(G)-nitro-L-arginine (L-NOARG), and of soluble guanylyl cyclase, 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ), reduced the electrical field stimulation-induced relaxations. Sildenafil and exogenous NO induced relaxations of penile small arteries. Sildenafil enhanced NO and vasoactive intestinal peptide-induced relaxations. Moreover, sildenafil increased the duration of the relaxations elicited by electrical field stimulation in penile small arteries and corpus cavernosum tissue. In the presence of L-NOARG, sildenafil only at supratherapeutic concentrations reduced the prazosin-sensitive contractions elicited by EFS in penile small arteries. Neurogenic NO-mediated and guanylyl cyclase-dependent relaxations of penile small arteries and corpus cavernosum tissue, considered to be associated with the vasodilatation leading to erection, are selectively enhanced by an inhibitor of phosphodiesterase V.