{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T17:12:28Z","timestamp":1762017148959},"reference-count":56,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":728,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2007,2]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>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\u2010induced release of nitric oxide (NO). In a previous study we found that the soluble guanylate cyclase (sGC)\/cyclic guanosine 3\u2019,5\u2019\u2013monophosphate (cGMP) pathway might modulate nerve\u2010induced release of NO in isolated cavernous tissue.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Electrical field stimulation (EFS 5\u2003Hz, 40\u2003V, 0.3 ms pulse duration, 25 pulses at intervals of 2\u2003min) of rabbit isolated cavernous tissue elicited reproducible, nerve\u2010mediated relaxations in the presence of scopolamine (10<jats:sup>\u22125<\/jats:sup>\u2003M), guanethidine (10<jats:sup>\u22125<\/jats:sup>\u2003M) and phenylephrine (3 \u00d7 10<jats:sup>\u22126<\/jats:sup>\u2003M). In superfusion experiments, nerve stimulation (20\u2003Hz, 40\u2003V, 1 ms) of the cavernous tissue evoked release of NO\/NO<jats:sub>2<\/jats:sub>\n<jats:sup>\u2212<\/jats:sup>, measured by chemiluminescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Sildenafil, tadalafil and vardenafil decreased the muscular tone and prolonged the relaxations to nerve stimulation. The evoked release of NO decreased to 72\u00b111%, 55\u00b116% and 61\u00b114% of control, respectively after addition of sildenafil, tadalafil or vardenafil (all 10<jats:sup>\u22124<\/jats:sup>\u2003M, n=6\u20138, p&lt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications:<\/jats:title><jats:p>Selective PDE 5 inhibitors influence the nerve\u2010induced release of NO, probably via cGMP\u2010mediated negative feedback. This negative feedback might explain why priapism is not seen during monotherapy with the PDE inhibitors.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2007) <jats:bold>150<\/jats:bold>, 353\u2013360. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0706991\">10.1038\/sj.bjp.0706991<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0706991","type":"journal-article","created":{"date-parts":[[2006,12,18]],"date-time":"2006-12-18T16:06:37Z","timestamp":1166457997000},"page":"353-360","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Inhibitors of phosphodiesterase 5 (PDE 5) inhibit the nerve\u2010induced release of nitric oxide from the rabbit corpus 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