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Effects of Tolterodine on Afferent Neutransmission in Normal and Resiniferatoxin Treated conscious Rats
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences. (Lund University Hospital)
Lund.
Lund.
Lund/North Carolina.
2007 (English)In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 178, 326-331 p.Article in journal (Refereed) Published
Abstract [en]

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 μg kg−1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 μg kg−1 tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 μg 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.

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 μg kg−1 tolterodine administered intravenously increased the mean micturition interval, bladder capacity and micturition volume. In resiniferatoxin treated rats 1 and 10 μg kg−1 tolterodine increased the mean micturition interval, bladder capacity and micturition volume. Subcutaneous administration of 100 μg 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.

Place, publisher, year, edition, pages
2007. Vol. 178, 326-331 p.
Keyword [en]
bladder; tolterodine; urodynamics; nerve fibers, unmyelinated; rats, Sprague-
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-41177DOI: 10.1016/j.juro.2007.03.006Local ID: 55301OAI: oai:DiVA.org:liu-41177DiVA: diva2:262028
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13

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