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.
Simonsen
U
U
Department of Pharmacology, Faculty of Health Sciences, University of Aarhus, 8000 C, Aarhus, Denmark. us@farm.au,dk
Contreras
J
J
García-Sacristán
A
A
Martinez
A C
AC
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D004558:Electric Stimulation; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D010413:Penis / Q000098:blood supply* / Q000502:physiology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D009569:Nitric Oxide; D014660:Vasoactive Intestinal Peptide; D000068677:Sildenafil Citrate; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D010727:Phosphoric Diester Hydrolases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D000109:Acetylcholine