title: Phosphodiesterase 5 (PDE5) inhibition, ANP and NO rapidly reduce epididymal duct contractions, but long-term PDE5 inhibition in vivo does not.
abstract: Contractility of the peritubular smooth muscle layer ensures the transit of immotile spermatozoa through the epididymal duct to acquire their fertilizing capacity. Atrial natriuretic peptide (ANP) and nitric oxide (NO) affect contractility via cGMP signals that are controlled by phosphodiesterases (PDEs). Sildenafil inhibits the cGMP-hydrolyzing PDE5 and thereby promotes relaxation of smooth muscle cells. While sildenafil is increasingly used in young patients for the treatment of pulmonary hypertension, virtually no knowledge exists about PDEs in the epididymis. Western blotting, immunohistochemistry and RT-PCR analyses after laser capture microdissection localized PDE5 to smooth muscle cells, but not to epithelial cells, of the epididymal duct in man and rat. Sildenafil, ANP and NO significantly slowed spontaneous contractions of rat epididymal duct segments in organ bath studies. Sildenafil effects were additive to ANP and NO. Long-term exposure to sildenafil in vivo did not change the PDE5 expression or the observed contractility pattern with the rapid relaxing response toward ANP, NO and sildenafil. Data demonstrate that PDE5 is an important member of cGMP signaling pathways regulating the finely orchestrated process of epididymal duct contractility and suggest, however, that in the epididymis side effects of therapeutically used sildenafil are unlikely.
authors: Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, 35385 Giessen, Germany.
authors: Andrea
authors: A
authors: Mietens
authors: Sabine
authors: S
authors: Tasch
authors: Caroline
authors: C
authors: Feuerstacke
authors: Gerrit
authors: G
authors: Eichner
authors: Johanna
authors: J
authors: Volkmann
authors: Ralph Theo
authors: RT
authors: Schermuly
authors: Friedrich
authors: F
authors: Grimminger
authors: Dieter
authors: D
authors: Müller
authors: Ralf
authors: R
authors: Middendorff
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000235:genetics / Q000378:metabolism*; D004822:Epididymis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009924:Organ Culture Techniques; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D011687:Purines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D020030:Nitric Oxide Donors; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D012333:RNA, Messenger; D013450:Sulfones; D009599:Nitroprusside; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D000068677:Sildenafil Citrate; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D006152:Cyclic GMP