Nicorandil ameliorates hypertension-related bladder dysfunction in the rat.

Abstract

AIMS:

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: Motoaki Saito, Fumiya Ohmasa, Panagiota Tsounapi, Seiya Inoue, Fotios Dimitriadis, Yukako Kinoshita, Keisuke Satoh
• Journal: Neurourology and urodynamics (Neurourol Urodyn) Vol. 31 Issue 5 Pg. 695-701 (Jun 2012) ISSN: 1520-6777 [Electronic] United States
• PMID: 22473863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• Antihypertensive Agents
• KATP Channels
• Kir6.2 channel
• Potassium Channels, Inwardly Rectifying
• RNA, Messenger
• uK-ATP-1 potassium channel
• Nicorandil
• Nerve Growth Factor

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Blood Pressure (drug effects)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Hypertension (complications, drug therapy, genetics, physiopathology)
• KATP Channels (drug effects, genetics, metabolism)
• Male
• Nerve Growth Factor (metabolism)
• Nicorandil (pharmacology)
• Potassium Channels, Inwardly Rectifying (drug effects, genetics, metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Inbred SHR
• Rats, Wistar
• Real-Time Polymerase Chain Reaction
• Regional Blood Flow (drug effects)
• Reverse Transcriptase Polymerase Chain Reaction
• Time Factors
• Urinary Bladder (blood supply, drug effects, innervation, metabolism, physiopathology)
• Urinary Bladder, Overactive (etiology, genetics, physiopathology, prevention & control)
• Urination (drug effects)
• Urodynamics (drug effects)