title: Comparison of the effects of β3 -adrenoceptor agonism on urinary bladder function in conscious, anesthetized, and spinal cord injured rats.
abstract: OBJECTIVE
  To compare the dose effect relationship of a selective β3 -adrenoceptor agonist (CL-316,243) on cystometric parameters in anesthetized and conscious rats and to evaluate its effect in a model of neurogenic bladder overactivity induced by spinal cord injury (SCI).
  
  
  METHODS
  Experiments were performed in anesthetized and conscious normal rats and in conscious rats after complete transection at the T8 level of the spinal cord. The jugular vein and urinary bladder were catheterized and the bladder infused with saline. CL-316,243 was tested intravenously at 0.01, 0.03, and 0.1 mg/kg in anesthetized and conscious rats and at 0.01 mg/kg in sham and SCI rats. Intravesical pressure was recorded for 1 hr following drug administration. Intercontraction interval (ICI), amplitude of micturition (AM), micturition frequency (MF) and non-voiding contractions (NVC) were analyzed.
  
  
  RESULTS
  In anesthetized and conscious normal rats, CL-316,243 significantly increased ICI in a dose-dependent manner. In anesthetized rats, AM was significantly decreased at all doses tested whereas in conscious rats, a significant decrease (-19 ± 6%) in AM was only observed at the highest dose (0.1 mg/kg). In conscious sham and SCI rats, CL-316,243 significantly increased ICI (42 ± 17% and 49 ± 17%, respectively) and decreased MF without affecting AM. In SCI rats, CL-316,243 reduced the frequency of NVC (-53 ± 14%) without significant effects on amplitude.
  
  
  CONCLUSIONS
  The current results suggest that anesthesia can alter the effects of β3 -adrenoceptor agonists in experimental models. In addition, this is the first demonstration that stimulation of β3 -adrenoceptors can produce decreases in micturition frequency and NVC in SCI rats without affecting AM.
authors.affiliation: UROsphere, Faculty of Pharmaceutical Sciences, Toulouse, France.|Department of Urology, Andrology and Renal Transplantation, Rangueil University Hospital, Toulouse, France.
authors.forename: J B
authors.initials: JB
authors.lastname: Beauval
authors.affiliation: UROsphere, Faculty of Pharmaceutical Sciences, Toulouse, France.
authors.forename: V
authors.initials: V
authors.lastname: Guilloteau
authors.affiliation: UROsphere, Faculty of Pharmaceutical Sciences, Toulouse, France.
authors.forename: M
authors.initials: M
authors.lastname: Cappellini
authors.affiliation: UROsphere, Faculty of Pharmaceutical Sciences, Toulouse, France.
authors.forename: T D
authors.initials: TD
authors.lastname: Westfall
authors.affiliation: UROsphere, Faculty of Pharmaceutical Sciences, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Rischmann
authors.affiliation: UROsphere, Faculty of Pharmaceutical Sciences, Toulouse, France.
authors.forename: S
authors.initials: S
authors.lastname: Palea
authors.affiliation: UROsphere, Faculty of Pharmaceutical Sciences, Toulouse, France.|Department of Urology, Andrology and Renal Transplantation, Rangueil University Hospital, Toulouse, France.|INSERM I2MC, Rangueil University Hospital, Toulouse, France.
authors.forename: X
authors.initials: X
authors.lastname: Gamé
authors.affiliation: UROsphere, Faculty of Pharmaceutical Sciences, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Lluel
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D003243:Consciousness; D004149:Dioxoles / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D001743:Urinary Bladder / Q000187:drug effects*; D053201:Urinary Bladder, Overactive / Q000503:physiopathology; D014554:Urination / Q000187:drug effects / Q000502:physiology; D014563:Urodynamics / Q000187:drug effects
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D004149:Dioxoles; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
keywords: cystometry; neurogenic overactivity; overactive bladder; spinal cord injury; β3-adrenoceptor agonist