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Effects of beta(3)-adrenoceptor stimulation on prostaglandin E-2-induced bladder hyperactivity and on the cardiovascular system in conscious rats

Takeda, H; Yamazaki, Y; Igawa, Y; Kaidoh, K; Akahane, S; Miyata, H; Nishizawa, O; Akahane, M and Andersson, Karl-Erik LU (2002) In Neurourology and Urodynamics 21(6). p.558-565
Abstract
Aims. To investigate the effects of selective beta(2)- and selective beta(3)-adrenoceptor (AR) agonists on prostaglandin (PG) E-2-induced bladder hyperactivity in conscious free-moving rats. Methods. Female Sprague-Dawley rats were anesthetized for implantation of bladder, intravenous, and intra-arterial catheters. The effects of a beta(3)-AR agonist (CL316,243) on cystometric and cardiovascular parameters were assessed in conscious rats. Intravesical instillation of PGE(2) (20-60 muM, 6 mL/hr) in conscious rats produced a concentration-dependent increase in voiding frequency. Results. In this model i.v. CL316,243 (beta(3)-AR agonist) reduced basal bladder pressure, increased micturition volume, and prolonged micturition interval in a... (More)
Aims. To investigate the effects of selective beta(2)- and selective beta(3)-adrenoceptor (AR) agonists on prostaglandin (PG) E-2-induced bladder hyperactivity in conscious free-moving rats. Methods. Female Sprague-Dawley rats were anesthetized for implantation of bladder, intravenous, and intra-arterial catheters. The effects of a beta(3)-AR agonist (CL316,243) on cystometric and cardiovascular parameters were assessed in conscious rats. Intravesical instillation of PGE(2) (20-60 muM, 6 mL/hr) in conscious rats produced a concentration-dependent increase in voiding frequency. Results. In this model i.v. CL316,243 (beta(3)-AR agonist) reduced basal bladder pressure, increased micturition volume, and prolonged micturition interval in a dose-dependent manner, without affecting threshold pressure or micturition pressure. On the other hand, i.v. procaterol (beta(2)-AR agonist) did not counteract the bladder hyperactivity. Atropine (muscarinic antagonist) reduced micturition pressure and micturition volume, and shortened micturition interval. CL316,243 slightly decreased mean blood pressure and increased heart rate only when given at high doses (10 and 100 mug/kg, iv.). In contrast, procaterol caused a significant decrease in mean blood pressure and a significant increase in heart rate. Atropine significantly increased heart rate. Conclusions. The present results clearly demonstrated that the beta(3)-AR agonist prolonged the micturition interval without producing significant cardiovascular side effects. The human detrusor, like the rat detrusor, relaxes on beta(3)-AR stimulation. Provided that these results are valid in humans, selective beta(3)-AR agonists might be clinically useful for controlling a certain type of bladder overactivity. (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
frequent urination, bladder, overactive, prostaglandin E-2, beta(3)-adrenoceptor, cystometry, rat bladder
in
Neurourology and Urodynamics
volume
21
issue
6
pages
558 - 565
publisher
John Wiley & Sons
external identifiers
  • wos:000178800600008
  • pmid:12382247
  • scopus:0036400318
ISSN
0733-2467
DOI
10.1002/nau.10034
language
English
LU publication?
yes
id
5b8678e0-480c-438b-9b45-1866ffafd190 (old id 324684)
date added to LUP
2007-11-15 12:50:04
date last changed
2017-10-29 03:43:38
@article{5b8678e0-480c-438b-9b45-1866ffafd190,
  abstract     = {Aims. To investigate the effects of selective beta(2)- and selective beta(3)-adrenoceptor (AR) agonists on prostaglandin (PG) E-2-induced bladder hyperactivity in conscious free-moving rats. Methods. Female Sprague-Dawley rats were anesthetized for implantation of bladder, intravenous, and intra-arterial catheters. The effects of a beta(3)-AR agonist (CL316,243) on cystometric and cardiovascular parameters were assessed in conscious rats. Intravesical instillation of PGE(2) (20-60 muM, 6 mL/hr) in conscious rats produced a concentration-dependent increase in voiding frequency. Results. In this model i.v. CL316,243 (beta(3)-AR agonist) reduced basal bladder pressure, increased micturition volume, and prolonged micturition interval in a dose-dependent manner, without affecting threshold pressure or micturition pressure. On the other hand, i.v. procaterol (beta(2)-AR agonist) did not counteract the bladder hyperactivity. Atropine (muscarinic antagonist) reduced micturition pressure and micturition volume, and shortened micturition interval. CL316,243 slightly decreased mean blood pressure and increased heart rate only when given at high doses (10 and 100 mug/kg, iv.). In contrast, procaterol caused a significant decrease in mean blood pressure and a significant increase in heart rate. Atropine significantly increased heart rate. Conclusions. The present results clearly demonstrated that the beta(3)-AR agonist prolonged the micturition interval without producing significant cardiovascular side effects. The human detrusor, like the rat detrusor, relaxes on beta(3)-AR stimulation. Provided that these results are valid in humans, selective beta(3)-AR agonists might be clinically useful for controlling a certain type of bladder overactivity.},
  author       = {Takeda, H and Yamazaki, Y and Igawa, Y and Kaidoh, K and Akahane, S and Miyata, H and Nishizawa, O and Akahane, M and Andersson, Karl-Erik},
  issn         = {0733-2467},
  keyword      = {frequent urination,bladder,overactive,prostaglandin E-2,beta(3)-adrenoceptor,cystometry,rat bladder},
  language     = {eng},
  number       = {6},
  pages        = {558--565},
  publisher    = {John Wiley & Sons},
  series       = {Neurourology and Urodynamics},
  title        = {Effects of beta(3)-adrenoceptor stimulation on prostaglandin E-2-induced bladder hyperactivity and on the cardiovascular system in conscious rats},
  url          = {http://dx.doi.org/10.1002/nau.10034},
  volume       = {21},
  year         = {2002},
}