title: Protective effect of a β3-adrenoceptor agonist on bladder function in a rat model of chronic bladder ischemia.
abstract: BACKGROUND
  The β3-adrenoceptor (AR) agonist mirabegron has been introduced as a treatment for the overactive bladder. Its effects on the function of the ischemic bladder are not known.
  
  
  OBJECTIVE
  To investigate the effect of mirabegron in a rat model of chronic ischemia-related bladder dysfunction.
  
  
  METHODS
  Male Sprague-Dawley rats were divided into three groups: control (n=10), arterial endothelial injury (AI; n=16), and AI with mirabegron treatment (AI-mirabegron; n=10). AI and AI-mirabegron groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI. AI-mirabegron rats received mirabegron (10mg/kg/d) orally for 8 wk. The control group received a regular diet.
  
  
  METHODS
  After 8 wk, urodynamic investigation was performed in awake animals. Pharmacologic in vitro studies and histologic examination of the iliac arteries and bladders were performed.
  
  
  CONCLUSIONS
  Iliac arteries from both AI and AI-mirabegron rats displayed neointimal formation and luminal occlusion. Micturition interval (MI), bladder capacity (Bcap), and voided volume (VV) in the AI group were significantly less than in the control group (p<0.01). In the AI-mirabegron group, MI, Bcap, and VV were significantly larger than in the AI group (p<0.05) but significantly less than in the control group (p<0.05). Contractile responses of bladder strips to potassium chloride, electrical field stimulation, and carbachol were significantly lower after AI than in controls; responses in preparations from AI-mirabegron-treated animals were similar to those of controls. The AI group showed a significantly higher percentage of collagen (28.6 ± 1.57%) compared with the controls (8.65 ± 0.67%) and AI-mirabegron-treated animals (17.2 ± 2.32%). The mirabegron dose used in this study may potentially limit the translational value of the results.
  
  
  CONCLUSIONS
  In the chronically ischemic rat bladder, treatment with mirabegron seems to protect bladder function and morphology, resulting in reduced bladder hyperactivity. If the results are valid for humans, they support β3-AR agonism as a potential treatment of chronic ischemia-related bladder dysfunction.
authors.affiliation: Department of Urology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo City, Yamanashi, Japan.
authors.forename: Norifumi
authors.initials: N
authors.lastname: Sawada
authors.forename: Masanori
authors.initials: M
authors.lastname: Nomiya
authors.forename: Brandy
authors.initials: B
authors.lastname: Hood
authors.forename: David
authors.initials: D
authors.lastname: Koslov
authors.forename: Mona
authors.initials: M
authors.lastname: Zarifpour
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D000083:Acetanilides / Q000494:pharmacology*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D002791:Cholesterol, Dietary; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007083:Iliac Artery / Q000293:injuries / Q000473:pathology; D007511:Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D058426:Neointima; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D057772:Vascular System Injuries / Q000150:complications / Q000473:pathology
chemical_list: D000083:Acetanilides; D058667:Adrenergic beta-3 Receptor Agonists; D002791:Cholesterol, Dietary; D022702:Receptors, Adrenergic, beta-3; D013844:Thiazoles; D003094:Collagen; C520025:mirabegron
keywords: Arterial endothelial injury; Atherosclerosis; Cholesterol diet; Cystometry; Detrusor overactivity; Mirabegron