Document Detail


Effects of beta(3)-adrenoceptor stimulation on prostaglandin E(2)-induced bladder hyperactivity and on the cardiovascular system in conscious rats.
MedLine Citation:
PMID:  12382247     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 microM, 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 microg/kg, i.v.). 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.
Authors:
Hiroo Takeda; Yoshinobu Yamazaki; Yasuhiko Igawa; Kouichi Kaidoh; Satoshi Akahane; Hiroshi Miyata; Osamu Nishizawa; Masuo Akahane; Karl-Erik Andersson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurourology and urodynamics     Volume:  21     ISSN:  0733-2467     ISO Abbreviation:  Neurourol. Urodyn.     Publication Date:  2002  
Date Detail:
Created Date:  2002-10-16     Completed Date:  2003-01-15     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  8303326     Medline TA:  Neurourol Urodyn     Country:  United States    
Other Details:
Languages:  eng     Pagination:  558-65     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Affiliation:
Division of Discovery Research, Central Research Laboratory, Kissei Pharmaceutical Co., Ltd., Hotaka, Japan. hiroo.takeda@pharm.kissei.co.jp
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-3 Receptor Agonists
Adrenergic beta-Agonists / pharmacology*
Animals
Atropine / pharmacology
Blood Pressure / drug effects
Catheterization, Peripheral
Dinoprostone / physiology*
Dioxoles / pharmacology*
Dose-Response Relationship, Drug
Female
Heart Rate / drug effects
Muscarinic Antagonists / pharmacology
Pressure
Procaterol / pharmacology*
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, beta-2 / physiology*
Receptors, Adrenergic, beta-3 / physiology*
Urinary Bladder / drug effects,  physiology*,  physiopathology
Urinary Catheterization
Chemical
Reg. No./Substance:
0/Adrenergic beta-2 Receptor Agonists; 0/Adrenergic beta-3 Receptor Agonists; 0/Adrenergic beta-Agonists; 0/Dioxoles; 0/Muscarinic Antagonists; 0/Receptors, Adrenergic, beta-2; 0/Receptors, Adrenergic, beta-3; 138908-40-4/disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; 363-24-6/Dinoprostone; 51-55-8/Atropine; 72332-33-3/Procaterol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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