title: Antimuscarinic drug inhibits detrusor overactivity induced by topical application of prostaglandin E2 to the urethra with a decrease in urethral pressure.
abstract: OBJECTIVE
  Antimuscarinic drugs increase bladder capacity without prominent side effects such as urinary retention even when administered to patients with mild to moderate bladder outlet obstruction. Some mechanisms might exist in the urethra to compensate for the emptying function of the detrusor after the administration of antimuscarinic drugs. We investigated the influence of the antimuscarinic drug propiverine (Taiho Pharmaceutical, Tokyo, Japan) on urethral function.
  
  
  METHODS
  Urethral pressure and rhythmic bladder pressure were simultaneously monitored in urethane anesthetized female Sprague-Dawley rats. Prostaglandin E(2) was continuously administered intravesically or intraurethrally to induce detrusor overactivity. To eliminate the influence of bladder activity and monitor urethral baseline pressure isovolumetric pressure of the urethra was then recorded after cystectomy and ligation of the external urethral meatus. Furthermore, in vitro contractile responses of the urethral circular smooth muscle to field stimulation were examined in the presence of propiverine, tamsulosin (Taiho Pharmaceutical), verapamil, omega-conotoxin and atropine (Sigma).
  
  
  RESULTS
  Intravesical or intraurethral administration of prostaglandin E(2) significantly decreased the bladder contraction interval by 10.7% and 36.0%, respectively. Intra-arterial administration of 2 x 10(2) nM/kg propiverine significantly increased the bladder contraction interval in rats receiving intraurethral prostaglandin E(2) by 81.8% but it had no marked effect on rats receiving intravesical prostaglandin E(2). Significant decreases in urethral baseline pressure were found after propiverine administration. Field stimulation induced contraction was inhibited by propiverine and verapamil but not by tamsulosin, omega-conotoxin or atropine.
  
  
  CONCLUSIONS
  These results suggest that the inhibitory effects of propiverine are more prominent in rats with detrusor overactivity induced by intraurethral prostaglandin E(2) than by intravesical prostaglandin E(2). Propiverine may compensate for detrusor function by decreasing urethral resistance in the voiding phase.
authors.affiliation: Department of Urology, Faculty of Medical Science, University of Fukui, Fukui, Japan. oyoko@u-fukui.ac.jp
authors.forename: Osamu
authors.initials: O
authors.lastname: Yokoyama
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Miwa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oyama
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Aoki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ito
authors.forename: Hironobu
authors.initials: H
authors.lastname: Akino
mesh_terms: D000283:Administration, Intravesical; D000287:Administration, Topical; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000818:Animals; D001285:Atropine / Q000008:administration & dosage; D001561:Benzilates / Q000008:administration & dosage; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D018680:Cholinergic Antagonists / Q000008:administration & dosage; D015232:Dinoprostone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D007269:Injections, Intra-Arterial; D018727:Muscarinic Antagonists / Q000008:administration & dosage*; D009119:Muscle Contraction / Q000187:drug effects; D010120:Oxytocics / Q000008:administration & dosage; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage; D000077409:Tamsulosin; D016896:Treatment Outcome; D014521:Urethra / Q000187:drug effects / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000188:drug therapy* / Q000503:physiopathology; D014700:Verapamil / Q000008:administration & dosage; D020960:omega-Conotoxins / Q000008:administration & dosage
chemical_list: D000317:Adrenergic alpha-Antagonists; D001561:Benzilates; D002121:Calcium Channel Blockers; D018680:Cholinergic Antagonists; D018727:Muscarinic Antagonists; D010120:Oxytocics; D013449:Sulfonamides; D020960:omega-Conotoxins; C015586:propiverine; D001285:Atropine; D014700:Verapamil; D000077409:Tamsulosin; D015232:Dinoprostone