title: Relationship between connexin43-derived gap junction proteins in the bladder and age-related detrusor underactivity in rats.
abstract: OBJECTIVE
  To confirm the mechanisms of age-associated detrusor underactivity (DU), we examined the differences in bladder activity and connexin-43 (Cx43)-derived gap junctions in the bladders of young and old rats.
  
  
  METHODS
  Female Sprague-Dawley rats aged 3months (young) and 12months (old) were used. Continuous cystometry was performed under urethane anesthesia in both ages of rats. In addition, isovolumetric cystometry was performed in young rats during the intravesical application of carbenoxolone, a gap junction blocker, to confirm the role of gap junction proteins in the bladder. Western blotting analyses were performed to assess Cx43 protein expression in the bladders of both groups of rats. Bladders were also analyzed using Masson's trichrome staining and immunostaining for Cx43.
  
  
  RESULTS
  Cystometric evaluations revealed that compared with young rats, bladder contractility was reduced by 27% and residual urine volume was significantly increased in old rats. However, the intercontraction intervals did not differ between the two groups. Under isovolumetric conditions, bladder contraction was suppressed after the intravesical application of carbenoxolone. In the bladders of old rats, increase of smooth muscle cell hypertrophy and fibrous tissue was observed compared with young rats. In association with these findings, immunostaining for smooth muscle Cx43 and its protein level were decreased by 28% compared with young rats.
  
  
  CONCLUSIONS
  These results suggest that age-related DU might be caused by the downregulation of gap junctional intercellular communication in the bladder. Consequently, the normal signals that contribute to voiding function might not be transported between detrusor muscles.
authors.affiliation: Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Oshiro
authors.affiliation: Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan. Electronic address: miyaz929@med.u-ryukyu.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyazato
authors.affiliation: Department of Urology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Saito
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology; D000818:Animals; D015153:Blotting, Western; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000378:metabolism*; D015536:Down-Regulation; D005260:Female; D017629:Gap Junctions / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D001743:Urinary Bladder / Q000503:physiopathology*; D014554:Urination / Q000502:physiology
chemical_list: D018031:Connexin 43; D017630:Connexins; D002229:Carbenoxolone
keywords: Aging; Connexin43; Detrusor underactivity