Inhibitors of phosphodiesterase 5 (PDE 5) inhibit the nerve-induced release of nitric oxide from the rabbit corpus cavernosum
| Autor: | K, Hallén, N P, Wiklund, L E, Gustafsson |
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| Rok vydání: | 2006 |
| Předmět: |
Cyclic Nucleotide Phosphodiesterases
Type 5 Male Phosphodiesterase Inhibitors Triazines Imidazoles Muscle Smooth In Vitro Techniques Nitric Oxide Research Papers Piperazines Sildenafil Citrate Tadalafil Erectile Dysfunction Vardenafil Dihydrochloride 3' 5'-Cyclic-GMP Phosphodiesterases Purines Nitrergic Neurons Animals Rabbits Sulfones Priapism Cyclic GMP Carbolines Penis |
| Zdroj: | British journal of pharmacology. 150(3) |
| ISSN: | 0007-1188 |
| Popis: | 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.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 x 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.Sildenafil, tadalafil and vardenafil decreased the muscular tone and prolonged the relaxations to nerve stimulation. The evoked release of NO decreased to 72+/-11%, 55+/-16% and 61+/-14% of control, respectively after addition of sildenafil, tadalafil or vardenafil (all 10(-4) M, n=6-8, p0.05).Selective PDE 5 inhibitors influence the nerve-induced release of NO, probably via cGMP-mediated negative feedback. This negative feedback might explain why priapism is not seen during monotherapy with the PDE inhibitors. |
| Databáze: | OpenAIRE |
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