Nicorandil, a potassium channel opener and nitric oxide donor, improves the frequent urination without changing the blood pressure in rats with partial bladder outlet obstruction.
OBJECTIVE
It was studied to determine if nicorandil can improve frequent urination in rats with partial bladder outlet obstruction (BOO) without changing the blood pressure.


METHODS
Voiding behavior was observed 6 to 8 d after obstruction in female rats with BOO that loaded 30 ml/kg of water. A drug was administered orally. Changes in systemic blood pressure and heart rate were studied in conscious BOO rats using the tail cuff method.


RESULTS
The voiding frequency was increased and the average voided volume was decreased in BOO rats compared with normal rats. Nicorandil (1 mg/kg), cromakalim (0.1 mg/kg) and isosorbide dinitrate (ISDN; 1000 mg/kg) decreased voiding frequency significantly in BOO rats. Nicorandil also increased the average voided volume significantly. Although cromakalim and ISDN at doses effective at decreasing voiding frequency caused blood pressure to drop, nicorandil at an effective dose did not affect blood pressure and heart rate.


CONCLUSIONS
Nicorandil improved frequent urination without changing the blood pressure. These results suggested that a hybrid of a K(ATP) channel opener and nitric oxide donor, nicorandil was bladder-selective compared with vasculature in BOO rats.
Sudo
Hirokazu
H
Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan.
Yogo
Kenji
K
Ishizuka
Nobuhiko
N
Otsuka
Hideaki
H
Horie
Shigeo
S
Saito
Keiji
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D015640:Ion Channel Gating / Q000187:drug effects*; D020108:Nicorandil / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D020030:Nitric Oxide Donors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001748:Urinary Bladder Neck Obstruction / Q000150:complications* / Q000378:metabolism / Q000652:urine; D014555:Urination Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control* / Q000652:urine
D020030:Nitric Oxide Donors; D015221:Potassium Channels; D020108:Nicorandil