title: Sensory dysfunction of bladder mucosa and bladder oversensitivity in a rat model of metabolic syndrome.
abstract: OBJECTIVE
  To study the role of sensory dysfunction of bladder mucosa in bladder oversensitivity of rats with metabolic syndrome.
  
  
  METHODS
  Female Wistar rats were fed a fructose-rich diet (60%) or a normal diet for 3 months. Based on cystometry, the fructose-fed rats (FFRs) were divided into a group with normal detrusor function or detrusor overactivity (DO). Acidic adenosine triphosphate (ATP) solution (5mM, pH 3.3) was used to elicit reflex micturition. Cystometric parameters were evaluated before and after drug administration. Functional proteins of the bladder mucosa were assessed by western blotting.
  
  
  RESULTS
  Compared to the controls, intravesical acidic ATP solution instillation induced a significant increase in provoked phasic contractions in both FFR groups and a significant decrease in the mean functional bladder capacity of group DO. Pretreatment with capsaicin for C-fiber desentization, intravesical liposome for mucosal protection, or intravenous pyridoxal 5-phosphate 6-azophenyl-2',4'-disulfonic acid for antagonized purinergic receptors can interfere with the urodynamic effects of intravesical ATP in FFRs and controls. Over-expression of TRPV1, P2X(3), and iNOS proteins, and down-regulation of eNOS proteins were observed in the bladder mucosa of both fructose-fed groups.
  
  
  CONCLUSIONS
  Alterations of sensory receptors and enzymes in the bladder mucosa, including over-expression of TRPV1, P2X(3), and iNOS proteins, can precipitate the emergence of bladder phasic contractions and oversensitivity through the activation of C-afferents during acidic ATP solution stimulation in FFRs. The down-regulation of eNOS protein in the bladder mucosa of FFRs may lead to a failure to suppress bladder oversensitivity and phasic contractions. Sensory dysfunction of bladder mucosa and DO causing by metabolic syndrome are easier to elicit bladder oversensitivity to certain urothelium stimuli.
authors.affiliation: Division of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Wei-Chia
authors.initials: WC
authors.lastname: Lee
authors.forename: Po-Hui
authors.initials: PH
authors.lastname: Chiang
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
authors.forename: Chia-Ching
authors.initials: CC
authors.lastname: Wu
authors.forename: Yao-Chi
authors.initials: YC
authors.lastname: Chuang
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D008081:Liposomes; D024821:Metabolic Syndrome / Q000150:complications*; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D058920:Purinergic P2X Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D058469:Receptors, Purinergic P2X / Q000378:metabolism; D018689:Sensory System Agents / Q000008:administration & dosage / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology*; D053201:Urinary Bladder, Overactive / Q000209:etiology* / Q000503:physiopathology*
chemical_list: D008081:Liposomes; D058920:Purinergic P2X Receptor Antagonists; D058469:Receptors, Purinergic P2X; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D002211:Capsaicin