title: The effect of doxazosin and sildenafil citrate combination on bladder tissue contractility, alpha adrenergic receptor, and iNOS subtype expression in a male rat model of partially bladder outlet obstruction.
abstract: OBJECTIVE
  Our aim was to investigate the effects of doxazosin, sildenafil, and their combination on bladder tissue contractility and adrenergic receptor (AR) and inducible nitric oxide synthase (iNOS) expression utilizing a male rat model of partial urethral obstruction (PUO).
  
  
  METHODS
  Thirty male Sprague Dawley rats were divided into five groups. Except the SHAM group, all animals in remaining four groups underwent surgery for PUO. No further treatment was given to the first group (NT group). Remaining three groups received 6 weeks of treatment with 20 mg/kg doxazosin (D group), 20 mg/kg sildenafil (S group), 20 mg/kg doxazosin, and 20 mg/kg sildenafil combination (DS group), respectively via oral gavage. Then, bladder strips were harvested from each animal for isometric tension studies and for real time polymerase chain reaction studies of both AR subtypes and iNOS mRNA.
  
  
  RESULTS
  Contractile responses to carbachol and electrical field stimulation at various concentrations/frequencies showed a significant increase after PUO. Any treatment helped to normalize these increased responses. Alpha 1a and 1d AR subtype expressions were found to be down- and up-regulated, respectively, in every group with PUO, compared to SHAM group. iNOS expression was similar in D and NT groups and significantly increased in S and DS groups.
  
  
  CONCLUSIONS
  Contractile changes of rat bladder tissue due to PUO were prevented by sildenafil or doxazosin alone or in combination where combination treatment did not provide any additional advantage. Further studies are needed to clarify the role of phosphodiesterase inhibitors and combination treatment in the treatment of LUTS.
authors: Department of Urology, Marmara University School of Medicine, Istanbul, Turkey.
authors: Abdulkadir
authors: A
authors: Gumrah
authors: Department of Urology, Marmara University School of Medicine, Istanbul, Turkey.
authors: Yiloren
authors: Y
authors: Tanidir
authors: Department of Urology, Marmara University School of Medicine, Istanbul, Turkey.
authors: Ilker
authors: I
authors: Tinay
authors: Ergun Özalp Basic Research Laboratory, Marmara University School of Medicine, Istanbul, Turkey.
authors: Mustafa
authors: M
authors: Ozyurek
authors: Department of Urology, Marmara University School of Medicine, Istanbul, Turkey.
authors: Tufan
authors: T
authors: Tarcan
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004195:Disease Models, Animal; D017292:Doxazosin / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D000068677:Sildenafil Citrate / Q000494:pharmacology*; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism / Q000503:physiopathology*; D064804:Urological Agents / Q000494:pharmacology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D011942:Receptors, Adrenergic, alpha; D064804:Urological Agents; D002217:Carbachol; D000068677:Sildenafil Citrate; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D017292:Doxazosin
keywords: bladder outlet obstruction; doxazosin; isometric tension studies; receptors; sildenafil