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Urodynamic effects of a novel EP(1) receptor antagonist in normal rats and rats with bladder outlet obstruction.

Lee, Tack LU ; Hedlund, Petter LU ; Newgreen, Donald and Andersson, Karl-Erik LU (2007) In Journal of Urology 177(4). p.1562-1567
Abstract
Purpose: Prostaglandin E-2 and its EP1 receptor were suggested as endogenous modulators of bladder function in the normal physiological state and under pathophysiological conditions. We investigated if the new EP1 receptor antagonist PF-2907617-02 would influence the regulation of normal micturition in rats, and if it affects bladder function in animals with partial bladder outlet obstruction. Materials and Methods: The study was performed in normal female Sprague-Dawley rats and in rats with moderate, experimentally induced bladder outlet obstruction 2 weeks in duration. All animals underwent continuous cystometry in the awake state. PF-2907617-02 was given intravenously at doses of 0.1 and 1.0 mg/kg(-1) in normal rats, and at 1.0... (More)
Purpose: Prostaglandin E-2 and its EP1 receptor were suggested as endogenous modulators of bladder function in the normal physiological state and under pathophysiological conditions. We investigated if the new EP1 receptor antagonist PF-2907617-02 would influence the regulation of normal micturition in rats, and if it affects bladder function in animals with partial bladder outlet obstruction. Materials and Methods: The study was performed in normal female Sprague-Dawley rats and in rats with moderate, experimentally induced bladder outlet obstruction 2 weeks in duration. All animals underwent continuous cystometry in the awake state. PF-2907617-02 was given intravenously at doses of 0.1 and 1.0 mg/kg(-1) in normal rats, and at 1.0 mg/kg(-1) in bladder outlet obstructed animals. In a group of normal rats detrusor overactivity was produced by intravesical instillation of prostaglandin E-2. Results: In normal rats PF-2907617-02 (1 mg/kg(-1)) significantly increased bladder capacity, micturition volume and the micturition interval but it had no effect on other urodynamic parameters. The lower dose of PF-2907617 (0.1 mg/kg(-1)) showed no effect. Intravesical prostaglandin E-2 (50 mu M) induced detrusor overactivity. The antagonist significantly decreased the stimulatory effects of prostaglandin E-2 at 0.1 and 1.0 mg/kg(-1). In obstructed animals PF-2907617-02 significantly increased the micturition interval but not bladder capacity and residual volume. The drug also decreased the frequency and amplitude of nonvoiding contractions. Conclusions: EP1 receptor is involved in initiation of the micturition reflex in normal rats and in animals with bladder outlet obstruction. It may also contribute to the generation of detrusor overactivity after bladder outlet obstruction. Thus, EP1 receptor antagonists may have potential as treatment for detrusor overactivity in humans. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
dinoprostone, rats, Sprague-Dawley, muscle, smooth, bladder neck obstruction, bladder
in
Journal of Urology
volume
177
issue
4
pages
1562 - 1567
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000245090600089
  • scopus:33947207912
ISSN
1527-3792
DOI
10.1016/j.juro.2006.11.070
language
English
LU publication?
yes
id
de4c4684-30b2-4628-9154-b17988225e39 (old id 166245)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17382779&dopt=Abstract
date added to LUP
2007-07-05 12:20:24
date last changed
2017-09-24 04:31:13
@article{de4c4684-30b2-4628-9154-b17988225e39,
  abstract     = {Purpose: Prostaglandin E-2 and its EP1 receptor were suggested as endogenous modulators of bladder function in the normal physiological state and under pathophysiological conditions. We investigated if the new EP1 receptor antagonist PF-2907617-02 would influence the regulation of normal micturition in rats, and if it affects bladder function in animals with partial bladder outlet obstruction. Materials and Methods: The study was performed in normal female Sprague-Dawley rats and in rats with moderate, experimentally induced bladder outlet obstruction 2 weeks in duration. All animals underwent continuous cystometry in the awake state. PF-2907617-02 was given intravenously at doses of 0.1 and 1.0 mg/kg(-1) in normal rats, and at 1.0 mg/kg(-1) in bladder outlet obstructed animals. In a group of normal rats detrusor overactivity was produced by intravesical instillation of prostaglandin E-2. Results: In normal rats PF-2907617-02 (1 mg/kg(-1)) significantly increased bladder capacity, micturition volume and the micturition interval but it had no effect on other urodynamic parameters. The lower dose of PF-2907617 (0.1 mg/kg(-1)) showed no effect. Intravesical prostaglandin E-2 (50 mu M) induced detrusor overactivity. The antagonist significantly decreased the stimulatory effects of prostaglandin E-2 at 0.1 and 1.0 mg/kg(-1). In obstructed animals PF-2907617-02 significantly increased the micturition interval but not bladder capacity and residual volume. The drug also decreased the frequency and amplitude of nonvoiding contractions. Conclusions: EP1 receptor is involved in initiation of the micturition reflex in normal rats and in animals with bladder outlet obstruction. It may also contribute to the generation of detrusor overactivity after bladder outlet obstruction. Thus, EP1 receptor antagonists may have potential as treatment for detrusor overactivity in humans.},
  author       = {Lee, Tack and Hedlund, Petter and Newgreen, Donald and Andersson, Karl-Erik},
  issn         = {1527-3792},
  keyword      = {dinoprostone,rats,Sprague-Dawley,muscle,smooth,bladder neck obstruction,bladder},
  language     = {eng},
  number       = {4},
  pages        = {1562--1567},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Urodynamic effects of a novel EP(1) receptor antagonist in normal rats and rats with bladder outlet obstruction.},
  url          = {http://dx.doi.org/10.1016/j.juro.2006.11.070},
  volume       = {177},
  year         = {2007},
}