Inhibitory effects of nicorandil, a K ATP channel opener and a nitric oxide donor, on overactive bladder in animal models.
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.
Kamiyama
Yutaka
Y
Department of Urology, Teikyo University School of Medicine, Tokyo, Japan.
Muto
Satoru
S
Masuda
Hitoshi
H
Ide
Hisamitsu
H
Ishizuka
Nobuhiko
N
Saito
Keiji
K
Horie
Shigeo
S
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*
D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D020108:Nicorandil