title: The effect of bladder outlet obstruction on alpha1- and beta-adrenoceptor expression and function.
abstract: OBJECTIVE
  To explore possible changes in expression and/or function of alpha(1)- and beta-adrenoceptor subtypes as a cause for bladder dysfunction in a rat model of bladder outlet obstruction (BOO).
  
  
  METHODS
  BOO was induced in rats by partial urethral ligature. Contraction and relaxation experiments were performed with isolated bladder strips from BOO, sham-operated and non-operated (control) rats 7 days after BOO induction. mRNA expression of alpha(1)- and beta-adrenoceptor subtypes was assessed by quantitative real-time PCR.
  
  
  RESULTS
  Receptor-independent contraction or relaxation did not differ between BOO and sham rats. The alpha(1)-agonists methoxamine and A-61,603 caused only weak contraction without major differences between groups. Against KCl-induced tone, the beta-adrenoceptor agonists noradrenaline and isoprenaline caused similar relaxation in BOO and sham rats, whereas relaxation in response to the beta(3)-selective BRL 37,344 was attenuated. Against passive tension, noradrenaline induced relaxation in sham and control rats; in contrast, noradrenaline induced contraction at low concentrations and relaxation at high concentrations in BOO rats. The contraction component was abolished by the alpha(1)-antagonist prazosin. The mRNA expression of alpha(1D)-adrenoceptors was increased in BOO, whereas none of the other receptor mRNAs were up-regulated.
  
  
  CONCLUSIONS
  In a rat BOO model, weak contraction responses to alpha(1)-agonists and relaxation responses to beta-agonists are not altered to a major extent. Nevertheless, relaxation responses to the endogenous agonist noradrenaline are turned into alpha(1)-adrenoceptor-mediated contraction responses in BOO, possibly due to an up-regulation of alpha(1D)-adrenoceptors.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Maurits M
authors.initials: MM
authors.lastname: Barendrecht
authors.forename: Elfaridah P
authors.initials: EP
authors.lastname: Frazier
authors.forename: Wim
authors.initials: W
authors.lastname: Vrydag
authors.forename: Astrid E
authors.initials: AE
authors.lastname: Alewijnse
authors.forename: Stephan L M
authors.initials: SL
authors.lastname: Peters
authors.forename: Martin C
authors.initials: MC
authors.lastname: Michel
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D008026:Ligation; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis* / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis* / Q000502:physiology*; D012044:Regression Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism*
chemical_list: D000316:Adrenergic alpha-Agonists; D012333:RNA, Messenger; D018340:Receptors, Adrenergic, alpha-1; D011943:Receptors, Adrenergic, beta; D011189:Potassium Chloride; D009638:Norepinephrine