Urodynamic Effects of a Novel EP1 Receptor Antagonist in Normal Rats and Rats With Bladder Outlet Obstruction

Tack Lee, Petter Hedlund, Donald Newgreen, Karl Erik Andersson

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Purpose: Prostaglandin E2 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 E2. 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 E2 (50 μM) induced detrusor overactivity. The antagonist significantly decreased the stimulatory effects of prostaglandin E2 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.

Original languageEnglish
Pages (from-to)1562-1567
Number of pages6
JournalJournal of Urology
Volume177
Issue number4
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Urinary Bladder Neck Obstruction
Urodynamics
Urination
Urinary Bladder
Dinoprostone
Intravesical Administration
Residual Volume
Sprague Dawley Rats
Reflex
Pharmaceutical Preparations

Keywords

  • bladder
  • bladder neck obstruction
  • dinoprostone
  • muscle
  • rats
  • smooth
  • Sprague-Dawley

ASJC Scopus subject areas

  • Urology

Cite this

Urodynamic Effects of a Novel EP1 Receptor Antagonist in Normal Rats and Rats With Bladder Outlet Obstruction. / Lee, Tack; Hedlund, Petter; Newgreen, Donald; Andersson, Karl Erik.

In: Journal of Urology, Vol. 177, No. 4, 04.2007, p. 1562-1567.

Research output: Contribution to journalArticle

Lee, Tack ; Hedlund, Petter ; Newgreen, Donald ; Andersson, Karl Erik. / Urodynamic Effects of a Novel EP1 Receptor Antagonist in Normal Rats and Rats With Bladder Outlet Obstruction. In: Journal of Urology. 2007 ; Vol. 177, No. 4. pp. 1562-1567.
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abstract = "Purpose: Prostaglandin E2 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 E2. 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 E2 (50 μM) induced detrusor overactivity. The antagonist significantly decreased the stimulatory effects of prostaglandin E2 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.",
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AB - Purpose: Prostaglandin E2 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 E2. 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 E2 (50 μM) induced detrusor overactivity. The antagonist significantly decreased the stimulatory effects of prostaglandin E2 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.

KW - bladder

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KW - dinoprostone

KW - muscle

KW - rats

KW - smooth

KW - Sprague-Dawley

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