title: Progressive changes in detrusor function and micturition patterns with chronic bladder ischemia.
abstract: Lower urinary tract symptoms (LUTS) are bothersome constellation of voiding symptoms in men and women as they age. Multiple factors and comorbidities are attributed to this problem but underlying mechanisms of nonobstructive nonneurogenic detrusor overactivity, detrusor underactivity and LUTS remain largely unknown. Our goal was to characterize detrusor function and voiding patterns in relation to muscarinic receptors expression, nerve fiber density, and neural ultrastructure in chronic bladder ischemia.
  
  
  
  Iliac artery atherosclerosis and bladder ischemia were produced in male Sprague-Dawley rats. At 8 and 16 weeks after ischemia, micturition patterns and cystometrograms were recorded in conscious rats then bladder blood flow and nonvoiding spontaneous contractions were measured under general anesthesia. Bladder tissues were processed for Western blotting, immunostaining, and transmission electron microscopy.
  
  
  
  Bladder responses to ischemic insult depended on the duration of ischemia. Micturition patterns and cystometric changes at 8-week ischemia suggested detrusor overactivity, while voiding behavior and cystometrograms at 16-week ischemia implied abnormal detrusor function resembling underactivity. Upregulation of muscarinic M2 receptor was found after 8- and 16 weeks of ischemia. Downregulation of M3 and upregulation of M1 were detected at 16-week ischemia. Neural structural damage and marked neurodegeneration were found after 8 and 16 weeks of ischemia, respectively.
  
  
  
  Prolonged ischemia may be a mediating variable in progression of overactive bladder to dysfunctional patterns similar to detrusor underactivity. The mechanism appears to involve differential expression of M1, M2, and M3 receptors, neural structural injury, and progressive loss of nerve fibers.
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Zuohui
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Roya
authors.initials: R
authors.lastname: Azad
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Yang
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Mike B
authors.initials: MB
authors.lastname: Siroky
authors.affiliation: Department of Urology, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA.
authors.forename: Kazem M
authors.initials: KM
authors.lastname: Azadzoi
mesh_terms: D000818:Animals; D001369:Axons / Q000648:ultrastructure; D002908:Chronic Disease; D018450:Disease Progression; D007511:Ischemia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D009119:Muscle Contraction / Q000502:physiology; D009412:Nerve Fibers / Q000473:pathology; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology; D001743:Urinary Bladder / Q000098:blood supply* / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014554:Urination / Q000502:physiology*
chemical_list: D011976:Receptors, Muscarinic
keywords: Contraction; Ischemia; Urinary bladder; Urination