title: Presence of phosphodiesterase type 5 in the spinal cord and its involvement in bladder outflow obstruction related bladder overactivity.
abstract: OBJECTIVE
  Phosphodiesterase type 5 inhibitors were recently introduced as a new treatment option for men with lower urinary tract symptoms. Safety and clinical effectiveness are well documented but the mode of action is still unclear. We determined and compared the expression of phosphodiesterase type 5 in the spinal cord of normal (sham operated) rats and rats with partial urethral obstruction induced bladder overactivity. We also assessed the urodynamic effects of intravenously and intrathecally administered sildenafil in the rats to determine whether phosphodiesterase type 5 inhibitors exert effects on the sacral spinal cord.
  
  
  METHODS
  A total of 65 male Sprague-Dawley rats were used for molecular/morphological and functional experiments. Bladder overactivity was induced via surgical partial urethral obstruction in 39 of 65 rats. Spinal phosphodiesterase type 5 expression was assessed by histology and polymerase chain reaction. The effects of sildenafil administered intravenously or intrathecally were studied urodynamically.
  
  
  RESULTS
  Phosphodiesterase type 5 was expressed in various regions of the lumbosacral spinal cord, including the sacral regions of micturition control. Expression was similar in normal rats and rats with partial urethral obstruction/bladder overactivity. In normal rats intravenous and intrathecal sildenafil had no urodynamic effect. When administered intravenously and intrathecally to rats with partial urethral obstruction/bladder overactivity, sildenafil decreased micturition frequency and bladder pressure. Doses tested intrathecally had no effect when given intravenously.
  
  
  CONCLUSIONS
  Phosphodiesterase type 5 is expressed in the rat spinal cord. Intravenous sildenafil may exert part of its urodynamic effect in rats with partial urethral obstruction/bladder overactivity via an effect on the sacral spinal cord.
authors.affiliation: Department of Urology, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany; Walter Brendel Centre of Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany. Electronic address: claudius.fuellhase@med.uni-muenchen.de.
authors.forename: Claudius
authors.initials: C
authors.lastname: Füllhase
authors.forename: Martin
authors.initials: M
authors.lastname: Hennenberg
authors.forename: Armin
authors.initials: A
authors.lastname: Giese
authors.forename: Michael
authors.initials: M
authors.lastname: Schmidt
authors.forename: Frank
authors.initials: F
authors.lastname: Strittmatter
authors.forename: Roberto
authors.initials: R
authors.lastname: Soler
authors.forename: Christian
authors.initials: C
authors.lastname: Gratzke
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
authors.forename: Christian
authors.initials: C
authors.lastname: Stief
mesh_terms: D000818:Animals; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013116:Spinal Cord / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D001748:Urinary Bladder Neck Obstruction / Q000150:complications*; D053201:Urinary Bladder, Overactive / Q000209:etiology*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5
keywords: BC; BCap; BO; BP; Ct; GAPDH; IC; IMI; IMP; L-NAME; LUTS; MMP; MV; N-nitro-L-arginine methyl ester; NO; PCR; PDE5; PUO; RV; SA; TP; administration; basal bladder pressure; bladder capacity; bladder catheterization; bladder overactivity; cGMP; cyclic guanosine monophosphate; glyceraldehyde-3-phosphate dehydrogenase; injections; intermicturition interval; intermicturition pressure; intrathecal (subarachnoid) catheterization; intravenous; lower urinary tract symptoms; maximum micturition pressure; micturition volume; nitric oxide; partial urethral obstruction; phosphodiesterase type 5; polymerase chain reaction; post-void residual volume; sildenafil; spinal; spontaneous bladder activity; threshold cycle; threshold pressure; urinary bladder