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Effects of Tolterodine on Afferent Neurotransmission in Normal and Resiniferatoxin Treated Conscious Rats.

Hedlund, Petter LU ; Streng, Tomi LU ; Lee, Tack LU and Andersson, Karl-Erik LU (2007) In Journal of Urology 178(1). p.326-331
Abstract
Purpose: The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters. Materials and Methods: The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the... (More)
Purpose: The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters. Materials and Methods: The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the drug was given to normal and resiniferatoxin treated animals in which detrusor activity was induced by apomorphine. Results: In resiniferatoxin treated animals (0.3 mg kg(-1) subcutaneously) the mean micturition interval and volume, and mean residual volume increased significantly compared to those in controls. Baseline and micturition pressures in control and resiniferatoxin treated animals were similar, whereas threshold pressures were higher in resiniferatoxin treated animals. In controls 10 kg kg-1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 Ag kg(-1) tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 mu g kg(-1) apomorphine induced detrusor overactivity in all rats. The AUC of intravesical pressure during the initial 10 minutes from the start of detrusor overactivity showed no difference between normal and resiniferatoxin treated rats with or without tolterodine pretreatment. Conclusions: Tolterodine increased the micturition interval and bladder capacity in controls and in resiniferatoxin treated animals, suggesting that these effects were exerted independently of resiniferatoxin sensitive afferents. Tolterodine did not decrease the contractile effects of apomorphine at the doses used, suggesting that the drug had no effect on efferent neurotransmission during voiding. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Urology
volume
178
issue
1
pages
326 - 331
publisher
Lippincott Williams & Wilkins
external identifiers
  • wos:000247197000092
  • scopus:34250195782
ISSN
1527-3792
DOI
10.1016/j.juro.2007.03.006
language
English
LU publication?
yes
id
6295b299-f0da-4ceb-9e05-993ca51bc65f (old id 168257)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17507042&dopt=Abstract
date added to LUP
2007-07-05 09:50:26
date last changed
2017-01-01 06:58:30
@article{6295b299-f0da-4ceb-9e05-993ca51bc65f,
  abstract     = {Purpose: The beneficial effects of antimuscarinics on detrusor overactivity and overactive bladder syndrome are exerted during bladder filling, when there is no parasympathetic outflow from the spinal cord. We tested the hypothesis that, if tolterodine exerts some of its effects on afferent nerves, the functional elimination of C-fiber afferents should affect the actions of the drug on urodynamic parameters. Materials and Methods: The study was performed in normal female Sprague Dawley rats and rats treated with resiniferatoxin to eliminate vanilloid sensitive afferent nerves. Tolterodine was given intravenously to normal and resiniferatoxin treated animals. To test if tolterodine at the doses used affects efferent neurotransmission the drug was given to normal and resiniferatoxin treated animals in which detrusor activity was induced by apomorphine. Results: In resiniferatoxin treated animals (0.3 mg kg(-1) subcutaneously) the mean micturition interval and volume, and mean residual volume increased significantly compared to those in controls. Baseline and micturition pressures in control and resiniferatoxin treated animals were similar, whereas threshold pressures were higher in resiniferatoxin treated animals. In controls 10 kg kg-1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 Ag kg(-1) tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 mu g kg(-1) apomorphine induced detrusor overactivity in all rats. The AUC of intravesical pressure during the initial 10 minutes from the start of detrusor overactivity showed no difference between normal and resiniferatoxin treated rats with or without tolterodine pretreatment. Conclusions: Tolterodine increased the micturition interval and bladder capacity in controls and in resiniferatoxin treated animals, suggesting that these effects were exerted independently of resiniferatoxin sensitive afferents. Tolterodine did not decrease the contractile effects of apomorphine at the doses used, suggesting that the drug had no effect on efferent neurotransmission during voiding.},
  author       = {Hedlund, Petter and Streng, Tomi and Lee, Tack and Andersson, Karl-Erik},
  issn         = {1527-3792},
  language     = {eng},
  number       = {1},
  pages        = {326--331},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {Journal of Urology},
  title        = {Effects of Tolterodine on Afferent Neurotransmission in Normal and Resiniferatoxin Treated Conscious Rats.},
  url          = {http://dx.doi.org/10.1016/j.juro.2007.03.006},
  volume       = {178},
  year         = {2007},
}