title: Pathways Involving Beta-3 Adrenergic Receptors Modulate Cold Stress-Induced Detrusor Overactivity in Conscious Rats.
abstract: OBJECTIVE
  To investigate pathways involving beta-3 adrenergic receptors (ARs) in detrusor overactivity induced by cold stress, we determined if the beta-3 AR agonist CL316243 could modulate the cold stress-induced detrusor overactivity in normal rats.
  
  
  METHODS
  Two days prior to cystometric investigations, the bladders of 10-week-old female Sprague-Dawley rats were cannulated. Cystometric measurements of the unanesthetized, unrestricted rats were taken to estimate baseline values at room temperature (RT, 27 ± 2 °C) for 20 min. They were then intravenously administered vehicle, 0.1, or 1.0 mg/kg CL316243 (n = 6 in each group). Five minutes after the treatments, they were gently and quickly transferred to the low temperature (LT, 4 ± 2 °C) room for 40 min where the cystometric measurements were again made. Afterward, the rats were returned to RT for final cystometric measurements. The cystometric effects of CL316243 were also measured at RT (n = 6 in each group).
  
  
  RESULTS
  At RT, both low and high dose of CL316243 decreased basal and micturition pressure while the high dose (1.0 mg/kg) significantly increased voiding interval and bladder capacity. During LT exposure, the high dose of CL316243 partially reduced cold stress-induced detrusor overactivity characterized by increased basal pressure and urinary frequency. The high drug dose also significantly inhibited the decreases of both voiding interval and bladder capacity compared to the vehicle- and low dose (0.1 mg/kg)-treated rats.
  
  
  CONCLUSIONS
  A high dose of the beta-3 agonist CL316243 could modulate cold stress-induced detrusor overactivity. Therefore, one of the mechanisms in cold stress-induced detrusor overactivity includes a pathway involving beta-3 ARs.
authors.affiliation: Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, Matsumoto, Japan.|Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishizuka
authors.affiliation: Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamagishi
authors.affiliation: Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yokoyama
authors.affiliation: Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Minagawa
authors.affiliation: Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakazawa
authors.affiliation: Department of Lower Urinary Tract Medicine, Shinshu University School of Medicine, Matsumoto, Japan.|Department of Urology, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishizawa
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003080:Cold Temperature / Q000009:adverse effects*; D003243:Consciousness; D004149:Dioxoles / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D013312:Stress, Physiological / Q000502:physiology*; D053201:Urinary Bladder, Overactive / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D015415:Biomarkers; D004149:Dioxoles; D022702:Receptors, Adrenergic, beta-3; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate
keywords: Sprague-Dawley rat; beta-3 adrenergic receptor; cold stress; detrusor overactivity; lower urinary tract symptoms