title: Nicorandil ameliorates hypertension-related bladder dysfunction in the rat.
abstract: OBJECTIVE
  There is increasing evidence that ischemia is one of the main etiology in overactive bladder (OAB), and that nicorandil prevents OAB. We investigated the effect of nicorandil on hypertension-related bladder dysfunction in spontaneously hypertensive rats (SHRs).
  
  
  METHODS
  Twelve-week-old SHRs received six-weeks treatment with nicorandil (0, 3, or 10 mg/kg, i.p. every day). Wistar rats were used for normotensive controls. Six weeks after nicorandil treatment, the bladder blood flow was estimated by hydrogen clearance method, and the bladder functions were estimated by voiding behavior studies and functional studies. Tissue levels of nerve growth factor (NGF) were measured by ELISA method. Furthermore, the participation levels of K(ATP) channel pores were investigated by real-time PCR.
  
  
  RESULTS
  SHRs showed significant increases in blood pressure, micturition frequency, tissue levels of NGF and expressions of both K(IR) 6.1 and K(IR) 6.2 mRNAs, and a significant decrease in the bladder blood flow. The carbachol-induced contractile responses were similar in all groups. Although both doses of nicorandil failed to decrease the blood pressure, nicorandil significantly decreased the micturition frequency, tissue levels of NGF and increased the bladder blood flow in a dose dependent manner. The expressions of K(IR) 6.1 and K(IR) 6.2 mRNAs were slightly up-regulated by the low dose of nicorandil, whereas the high dose of nicorandil significantly up-regulated those expressions compared to non-treated SHRs.
  
  
  CONCLUSIONS
  These data indicate that nicorandil prevents hypertension-related bladder dysfunction in the SHR, which may be related to its effect on the increased blood flow in the bladder.
authors.affiliation: Division of Molecular Pharmacology, Tottori University School of Medicine, Yonago, Japan. saitomo@med.tottori-u.ac.jp
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
authors.forename: Fumiya
authors.initials: F
authors.lastname: Ohmasa
authors.forename: Panagiota
authors.initials: P
authors.lastname: Tsounapi
authors.forename: Seiya
authors.initials: S
authors.lastname: Inoue
authors.forename: Fotios
authors.initials: F
authors.lastname: Dimitriadis
authors.forename: Yukako
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Keisuke
authors.initials: K
authors.lastname: Satoh
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D054086:KATP Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D020108:Nicorandil / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012039:Regional Blood Flow / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D001743:Urinary Bladder / Q000098:blood supply / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000209:etiology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D014554:Urination / Q000187:drug effects; D014563:Urodynamics / Q000187:drug effects; D000099161:Kcnj11 Channel
chemical_list: D000959:Antihypertensive Agents; D054086:KATP Channels; D020932:Nerve Growth Factor; D020108:Nicorandil; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D000099161:Kcnj11 Channel; C092520:uK-ATP-1 potassium channel