title: Alpha1-adrenoceptor antagonists improve bladder storage function through reduction of afferent activity in rats with bladder outlet obstruction.
abstract: OBJECTIVE
  Using a rat BOO model, we determined whether α1-adrenoceptor (AR) antagonists (silodosin, prazosin) improve the bladder storage function by reducing afferent input from the lower urinary tract.
  
  
  METHODS
  Male rats received partial bladder outlet obstruction or sham surgery were used. Four weeks following surgery, their voiding behavior was measured in a metabolic cage. BOO-rats were administered silodosin, prazosin or vehicle for 2 weeks subcutaneously using osmotic pump. At the post-drug condition, voiding behavior was measured again. The L6 spinal cord was removed and immunostained using anti c-Fos antibody. The rats were also performed continuous cystometry with saline without anesthesia or restraint at the pre- and post-drug conditions.
  
  
  RESULTS
  Metabolic cage study showed the voiding behavior of BOO-rats was characterized by increase in frequency of urination and decrease in volume voided. Cystometric evaluation also showed the significant increase both in the number of successive voiding contraction and in contraction pressure. The administration of silodosin or prazosin significantly decreased urinary frequency and the number of micturition reflex but affected neither bladder contraction pressure nor residual volume. The number of c-Fos-positive cell significantly increased in BOO-rats, while significantly decreased in those receiving αl-AR antagonists.
  
  
  CONCLUSIONS
  The present study demonstrates that α1-AR antagonists silodosin and prazosin have an inhibitory effect on afferent input from the lower urinary tract independently of reducing urethral resistance, and thereby reduce the storage dysfunction secondary to BOO. This result suggests that αl-AR, particularly αlA-AR, may play an important role in the activation of the afferent pathway.
authors.affiliation: Department of Urology, Fukushima Medical University, Fukushima, Japan. yazaki@fmu.ac.jp
authors.forename: Junji
authors.initials: J
authors.lastname: Yazaki
authors.forename: Ken
authors.initials: K
authors.lastname: Aikawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Shishido
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Yanagida
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.forename: Kei
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Haga
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamaguchi
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000344:Afferent Pathways / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D055104:Infusions, Subcutaneous; D008161:Lumbosacral Region; D008297:Male; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D011312:Pressure; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism; D012018:Reflex / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D001748:Urinary Bladder Neck Obstruction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D016760:Proto-Oncogene Proteins c-fos; D018340:Receptors, Adrenergic, alpha-1; C095285:silodosin; D011224:Prazosin