title: Inhibitory effects of nicorandil, a K ATP channel opener and a nitric oxide donor, on overactive bladder in animal models.
abstract: OBJECTIVE
  To investigate the effects of nicorandil, an ATP-sensitive potassium (K(ATP)) channel opener with a nitric oxide (NO) donor property, on overactive bladder (OAB) in animal models. Nicorandil is currently used clinically to treat ischaemic heart disease.
  
  
  METHODS
  Three animal OAB models were used: (i) C-fibre mediated bladder overactivity by infusion of a low concentration of acetic acid (AA) into the bladder in female Wistar rats; (ii) bladder outlet obstruction (BOO) created by partial urethral obstruction in female Wistar rats; and (iii) neuronal NO synthase (nNOS) knockout (KO) mice with urinary frequency. The effects of nicorandil and KRN2391, both of which act as K(ATP) channel openers and NO donors, on the OAB models were examined.
  
  
  RESULTS
  Cystometry showed that intravesical instillation of nicorandil and KRN2391 successfully inhibited OAB induced by intravesical instillation of AA. In the BOO model compared with untreated BOO rats, both nicorandil (1 and 3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency. Compared with wild-type mice, nNOS KO mice had urinary frequency with no change in the total urine volume. Nicorandil (3 mg/kg, orally) and KRN2391 (1 mg/kg, orally) significantly reduced the voiding frequency in nNOS KO mice.
  
  
  CONCLUSIONS
  Our in vivo results show that nicorandil, a K(ATP) channel opener with a NO donor property, can suppress OAB from both neurogenic and myogenic causes. Nicorandil appears to be a promising candidate for clinical use in patients with OAB.
authors: Department of Urology, Teikyo University School of Medicine, Tokyo, Japan.
authors: Yutaka
authors: Y
authors: Kamiyama
authors: Satoru
authors: S
authors: Muto
authors: Hitoshi
authors: H
authors: Masuda
authors: Hisamitsu
authors: H
authors: Ide
authors: Nobuhiko
authors: N
authors: Ishizuka
authors: Keiji
authors: K
authors: Saito
authors: Shigeo
authors: S
authors: Horie
mesh_terms: D000283:Administration, Intravesical; D000818:Animals; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D020108:Nicorandil / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D001748:Urinary Bladder Neck Obstruction / Q000150:complications / Q000503:physiopathology; D053201:Urinary Bladder, Overactive / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D014563:Urodynamics / Q000502:physiology*
chemical_list: D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D020108:Nicorandil