Advanced

Effects of the Gonadotropin-Releasing Hormone Antagonist Ganirelix on Normal Micturition and Prostaglandin E-2-Induced Detrusor Overactivity in Conscious Female Rats

Russo, Andrea; Castiglione, Fabio; Salonia, Andrea; Benigni, Fabio; Rigatti, Patrizio; Montorsi, Francesco; Andersson, Karl-Erik LU and Hedlund, Petter LU (2011) In European Urology 59(5). p.868-874
Abstract
BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonists have been reported to have beneficial effects on lower urinary tract symptoms in patients with benign prostatic hyperplasia. OBJECTIVE: Our aim was to investigate the effects of ganirelix, a GnRH receptor antagonist, on bladder function and detrusor overactivity (DO) in female rats. DESIGN, SETTING, AND PARTICIPANTS: Female Sprague-Dawley rats received 2 wk of daily systemic (0.1mg/kg) or acute intravesical administration (IVES; 0.14mg/l or 1.4mg/l) ganirelix or vehicle (controls). MEASUREMENTS: Assessments were obtained using cystometry in awake rats, organ bath studies, enzyme-linked immunosorbent assay, and western blot (WB). RESULTS AND LIMITATIONS: Luteinising hormone... (More)
BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonists have been reported to have beneficial effects on lower urinary tract symptoms in patients with benign prostatic hyperplasia. OBJECTIVE: Our aim was to investigate the effects of ganirelix, a GnRH receptor antagonist, on bladder function and detrusor overactivity (DO) in female rats. DESIGN, SETTING, AND PARTICIPANTS: Female Sprague-Dawley rats received 2 wk of daily systemic (0.1mg/kg) or acute intravesical administration (IVES; 0.14mg/l or 1.4mg/l) ganirelix or vehicle (controls). MEASUREMENTS: Assessments were obtained using cystometry in awake rats, organ bath studies, enzyme-linked immunosorbent assay, and western blot (WB). RESULTS AND LIMITATIONS: Luteinising hormone levels were lower in rats treated systemically with ganirelix than in controls. No differences were observed in body or bladder weights. Micturition interval (MI), micturition volume (MV), residual volume, and bladder capacity (BC) were similar in both groups at baseline. No differences in urodynamic pressure parameters were observed between groups at baseline. Intravesical prostaglandin E(2) reduced MI, MV, and BC, and it increased basal pressure (BP), threshold pressure (TP), flow pressure (FP), and maximum pressure (MP) in all rats. MI, MV, and BC were reduced by 43%±4%, 50%±4%, and 43%±4% (controls) versus 22%±3%, 23%±3%, and 21%±3% (ganirelix-treated rats; p<0.001). TP and FP increased by 38%±8% and 30%±4% (controls) versus 16%±7% and 16%±5% (ganirelix; p<0.05). The maximal force of contractions for carbachol was larger in detrusor from ganirelix-treated rats (231% vs 177% of 60mM K+-induced contractions). At 0.14mg/l, but not 0.14mg/l, IVES ganirelix increased MI, MV, and BC and decreased BP, TP, FP, and MP. In vitro, ganirelix had no effect on detrusor function. The gonadotropin-releasing hormone receptor was expressed (by WB) in the bladder mucosa. CONCLUSIONS: Systemic treatment with ganirelix counteracted experimental DO in female rats. Because bladder preparations from these rats exhibited larger contractions to carbachol and because intravesical ganirelix affected both micturition intervals and urodynamic pressure profiles, a peripheral site of action of ganirelix in the urinary bladder cannot be excluded. (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
Receptor, GnRH, Mucosa, Western blot, Antagonist, Systemic, Intravesical, Cystometry
in
European Urology
volume
59
issue
5
pages
868 - 874
publisher
Elsevier
external identifiers
  • wos:000288991500035
  • pmid:21196074
  • scopus:79953252914
ISSN
1873-7560
DOI
10.1016/j.eururo.2010.12.007
language
English
LU publication?
yes
id
c9613f51-2abc-4861-9360-2ab3a1fafcc1 (old id 1777923)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21196074?dopt=Abstract
date added to LUP
2011-02-01 10:12:53
date last changed
2017-09-24 04:13:41
@article{c9613f51-2abc-4861-9360-2ab3a1fafcc1,
  abstract     = {BACKGROUND: Gonadotropin-releasing hormone (GnRH) antagonists have been reported to have beneficial effects on lower urinary tract symptoms in patients with benign prostatic hyperplasia. OBJECTIVE: Our aim was to investigate the effects of ganirelix, a GnRH receptor antagonist, on bladder function and detrusor overactivity (DO) in female rats. DESIGN, SETTING, AND PARTICIPANTS: Female Sprague-Dawley rats received 2 wk of daily systemic (0.1mg/kg) or acute intravesical administration (IVES; 0.14mg/l or 1.4mg/l) ganirelix or vehicle (controls). MEASUREMENTS: Assessments were obtained using cystometry in awake rats, organ bath studies, enzyme-linked immunosorbent assay, and western blot (WB). RESULTS AND LIMITATIONS: Luteinising hormone levels were lower in rats treated systemically with ganirelix than in controls. No differences were observed in body or bladder weights. Micturition interval (MI), micturition volume (MV), residual volume, and bladder capacity (BC) were similar in both groups at baseline. No differences in urodynamic pressure parameters were observed between groups at baseline. Intravesical prostaglandin E(2) reduced MI, MV, and BC, and it increased basal pressure (BP), threshold pressure (TP), flow pressure (FP), and maximum pressure (MP) in all rats. MI, MV, and BC were reduced by 43%±4%, 50%±4%, and 43%±4% (controls) versus 22%±3%, 23%±3%, and 21%±3% (ganirelix-treated rats; p&lt;0.001). TP and FP increased by 38%±8% and 30%±4% (controls) versus 16%±7% and 16%±5% (ganirelix; p&lt;0.05). The maximal force of contractions for carbachol was larger in detrusor from ganirelix-treated rats (231% vs 177% of 60mM K+-induced contractions). At 0.14mg/l, but not 0.14mg/l, IVES ganirelix increased MI, MV, and BC and decreased BP, TP, FP, and MP. In vitro, ganirelix had no effect on detrusor function. The gonadotropin-releasing hormone receptor was expressed (by WB) in the bladder mucosa. CONCLUSIONS: Systemic treatment with ganirelix counteracted experimental DO in female rats. Because bladder preparations from these rats exhibited larger contractions to carbachol and because intravesical ganirelix affected both micturition intervals and urodynamic pressure profiles, a peripheral site of action of ganirelix in the urinary bladder cannot be excluded.},
  author       = {Russo, Andrea and Castiglione, Fabio and Salonia, Andrea and Benigni, Fabio and Rigatti, Patrizio and Montorsi, Francesco and Andersson, Karl-Erik and Hedlund, Petter},
  issn         = {1873-7560},
  keyword      = {Receptor,GnRH,Mucosa,Western blot,Antagonist,Systemic,Intravesical,Cystometry},
  language     = {eng},
  number       = {5},
  pages        = {868--874},
  publisher    = {Elsevier},
  series       = {European Urology},
  title        = {Effects of the Gonadotropin-Releasing Hormone Antagonist Ganirelix on Normal Micturition and Prostaglandin E-2-Induced Detrusor Overactivity in Conscious Female Rats},
  url          = {http://dx.doi.org/10.1016/j.eururo.2010.12.007},
  volume       = {59},
  year         = {2011},
}